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1.
Medicine (Baltimore) ; 103(28): e38860, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38996164

ABSTRACT

The purpose of the current study was to analyze whether aortic calcification had impact on the anastomotic leakage (AL) after rectal cancer (RC) surgery. We collected patients' information from January 2011 to January 2020 in a single teaching hospital. Preoperative computed tomography images were obtained. Abdominal aortic calcification (AAC), superior mesenteric aortic calcification, and inferior mesenteric aortic calcification were recorded. The difference of AL and grade C AL was calculated. A total of 2412 RC patients were included in this study. Ninety-seven (4.0%) RC patients experienced AL and 47 (1.9%) RC patients experienced grade C AL. The amount of AAC, superior mesenteric aortic calcification, and inferior mesenteric aortic calcification was 1546 (64.1%), 128 (5.3%), and 31 (1.3%). The AL group had higher portion of AAC (P = .019) than the no AL group, and the grade C AL group had higher portion of AAC (P = .016) than the no grade C AL group. In univariate logistic regression analysis, AAC was a significant potential factor for AL (P = .021, OR = 1.739, 95% CI = 1.088-2.779) and grade C AL (P = .019, OR = 2.339, 95% CI = 1.115-4.986). However, in multivariate logistic regression, AAC was not an independent predictive factor for AL (P = .157, OR = 1.443, 95% CI = 0.871-2.358) or grade C AL (P = .064, OR = 2.055, 95% CI = 0.960-4.399). AAC was associated with higher amount of AL and grade C AL, however, AAC was not an independent predictive factor for AL or grade C AL.


Subject(s)
Anastomotic Leak , Rectal Neoplasms , Vascular Calcification , Humans , Rectal Neoplasms/surgery , Rectal Neoplasms/pathology , Male , Female , Anastomotic Leak/etiology , Anastomotic Leak/epidemiology , Middle Aged , Aged , Vascular Calcification/diagnostic imaging , Retrospective Studies , Aorta, Abdominal/surgery , Aorta, Abdominal/diagnostic imaging , Tomography, X-Ray Computed , Aortic Diseases/surgery , Risk Factors
2.
J Cardiothorac Surg ; 19(1): 405, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38951901

ABSTRACT

BACKGROUND: The outcomes of Thoracic Endovascular Aortic Repair (TEVAR) vary depending on thoracic aortic pathologies, comorbidities. This study presents our comprehensive endovascular experience, focusing on exploring the outcome in long term follow-up. METHODS: From 2006 to 2018, we conducted TEVAR on 97 patients presenting with various aortic pathologies. This retrospective cohort study was designed primarily to assess graft durability and secondarily to evaluate mortality causes, complications, reinterventions, and the impact of comorbidities on survival using Kaplan-Meier and Cox regression analyses. RESULTS: The most common indication was thoracic aortic aneurysm (n = 52). Ten patients had aortic arch variations and anomalies, and the bovine arch was observed in eight patients. Endoleaks were the main complications encountered, and 10 of 15 endoleaks were type I endoleaks. There were 18 reinterventions; the most of which was TEVAR (n = 5). The overall mortality was 20 patients, with TEVAR-related causes accounting for 12 of these deaths, including intracranial bleeding in three patients. Multivariant Cox regression revealed chronic renal diseases (OR = 11.73; 95% CI: 2.04-67.2; p = 0.006), previous cardiac operation (OR = 14.26; 95% CI: 1.59-127.36; p = 0.01), and chronic obstructive pulmonary diseases (OR = 7.82; 95% CI: 1.43-42.78; p = 0.001) to be independent risk factors for 10-year survival. There was no significant difference in the survival curves of the various aortic pathologies. In the follow-up period, two non-symptomatic intragraft thromboses and one graft infection were found. CONCLUSION: Comorbidities can increase the risk of TEVAR-related mortality without significantly impacting endoleak rates. TEVAR is effective for severe aortic pathologies, though long-term graft durability may be compromised by its thrombosis and infection.


Subject(s)
Aorta, Thoracic , Endovascular Procedures , Humans , Retrospective Studies , Male , Female , Middle Aged , Endovascular Procedures/methods , Aorta, Thoracic/surgery , Aged , Blood Vessel Prosthesis Implantation/methods , Blood Vessel Prosthesis Implantation/adverse effects , Treatment Outcome , Aortic Diseases/surgery , Aortic Diseases/mortality , Postoperative Complications/epidemiology , Adult , Aortic Aneurysm, Thoracic/surgery , Aortic Aneurysm, Thoracic/mortality , Follow-Up Studies , Time Factors , Endovascular Aneurysm Repair
3.
Eur J Cardiothorac Surg ; 66(1)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38991832

ABSTRACT

OBJECTIVES: To report experience with a Relay® stent-graft custom-made platform in treating different aortic arch pathology in 2 high-volume aortic centres. METHODS: A retrospective analysis of all patients treated between July 2016 and July 2023 with custom-made Relay® stent-graft (custom-made device). Underlying aortic arch pathology was an aneurysm, penetrating aortic ulcer, and dissection. Three custom-made device designs were used: proximal scallop, fenestrations, and inner branches. The endpoints were technical success, perioperative stroke, death, and reintervention rate. RESULTS: Thirty-five patients (89% males) with a mean age of 70 ± 11 years were treated.Indication for treatment was penetrating aortic ulcer in 14 patients (40%), aneurysm in 11 patients (31%) and aortic dissection in 10 patients (29%). The technical success rate was 100%. Twenty-eight patients (80%) had proximal sealing in zone 0, and 7 (20%) had proximal sealing in zone 1. Nine patients (25.6%) had proximal scallops, 9 (25.6%) had 1 big fenestration and 17 (48.8%) had a branched device; 1 with single branch, 15 with double branches and 1 with triple branches. Thirty patients (86%) had previous or simultaneous left subclavian artery revascularization. No patient died during 30 days. Two patients (5.7%) had stroke postoperatively; both recovered without disabling deficits. The mean follow-up was 35 ± 26 months. Six patients (17.1%) died during follow-up. One patient required reinforcement of the bridging stent in the left common carotid artery and one additional vascular plugging of the left subclavian artery. Three patients received distal extension. CONCLUSIONS: The Relay® stent-graft custom-made platform showed a good performance in our study with a high technical success rate, low perioperative stroke and mortality, and low reintervention rates during the follow-up.


Subject(s)
Aorta, Thoracic , Blood Vessel Prosthesis Implantation , Blood Vessel Prosthesis , Prosthesis Design , Stents , Humans , Male , Aged , Female , Retrospective Studies , Aorta, Thoracic/surgery , Aorta, Thoracic/diagnostic imaging , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis Implantation/methods , Middle Aged , Treatment Outcome , Aged, 80 and over , Endovascular Procedures/methods , Endovascular Procedures/instrumentation , Aortic Diseases/surgery
5.
Arq Bras Cardiol ; 121(7): e20230805, 2024 Jun.
Article in Portuguese, English | MEDLINE | ID: mdl-39082580

ABSTRACT

BACKGROUND: Despite advances in diagnostic and treatment modalities, there is a need for predictive markers for recurrent strokes. OBJECTIVES: This study aimed to investigate the relationship between aortic arch calcification (AAC) and stroke recurrence in stroke patients during a one-year follow-up. METHODS: All stroke patients who experienced their first event were evaluated for participation in the study. Patients who experienced recurrent strokes during the one-year follow-up were recorded. AAC was assessed by chest radiography. Based on the occurrence of recurrent strokes the patients were divided into two groups. AAC was classified into four categories according to its degree, and the presence of AAC was included in the statistical analysis. The relationship between AAC and recurrent stroke was assessed using a receiver operating characteristic curve. A significance level of <0.05 was deemed acceptable for all statistical analyses. RESULTS: A total of 203 patients were included in the study (46.8% female, mean age 69±12.3). Recurrent stroke was detected in 49 patients. AAC, hypertension, and atrial fibrillation were more frequent in patients with recurrent stroke. Patients with recurrent stroke had a lower glomerular filtration rate and a higher red cell distribution width (RDW). In multivariate regression analysis, AAC (hazard ratio [HR], 3.544; 95% CI:1.653-7.598, p=0.001) and RDW (HR,1.214; 95% CI:1.053-1.400, p=0.008) were identified as independent predictors of recurrent stroke. CONCLUSION: The presence of AAC (≥ grade 1) and RDW were found to be significantly associated with the development of recurrent stroke within one year. These findings may have prognostic significance in the follow-up of stroke patients.


FUNDAMENTO: Apesar dos avanços nas modalidades de diagnóstico e tratamento, há necessidade de marcadores preditivos para acidente vascular cerebral (AVC) recorrentes. OBJETIVOS: Este estudo teve como objetivo investigar a relação entre calcificação do arco aórtico (CAA) e recorrência de AVC em pacientes com AVC durante o acompanhamento de um ano. MÉTODOS: Todos os pacientes com AVC que sofreram seu primeiro evento foram avaliados para participação no estudo. Foram registrados pacientes que sofreram AVC recorrentes durante o acompanhamento de um ano. A CAA foi avaliada por radiografia de tórax. Com base na ocorrência de AVC recorrente, os pacientes foram divididos em dois grupos. A CAA foi classificada em quatro categorias de acordo com o seu grau, e a presença de CAA foi incluída na análise estatística. A relação entre CAA e AVC recorrente foi avaliada por meio de uma curva característica de operação do receptor. Um nível de significância <0,05 foi considerado aceitável para todas as análises estatísticas. RESULTADOS: Um total de 203 pacientes foram incluídos no estudo (46,8% mulheres, média de idade 69±12,3). AVC recorrente foi detectado em 49 pacientes. CAA, hipertensão e fibrilação atrial foram mais frequentes em pacientes com AVC recorrente. Pacientes com AVC recorrente apresentaram menor taxa de filtração glomerular e maior largura de distribuição de glóbulos vermelhos (RDW). Na análise de regressão multivariada, CAA (hazard ratio [HR], 3,544; IC 95%:1,653-7,598, p=0,001) e RDW (HR,1,214; IC 95%:1,053-1,400, p=0,008) foram identificados como preditores independentes de AVC recorrente. CONCLUSÃO: A presença de CAA (≥ grau 1) e RDW foram significativamente associadas ao desenvolvimento de AVC recorrente dentro de um ano. Esses achados podem ter significado prognóstico no acompanhamento de pacientes com AVC.


Subject(s)
Aorta, Thoracic , Recurrence , Stroke , Humans , Female , Male , Aorta, Thoracic/diagnostic imaging , Aged , Stroke/diagnostic imaging , Middle Aged , Risk Factors , Vascular Calcification/diagnostic imaging , Aortic Diseases/diagnostic imaging , Radiography, Thoracic , Aged, 80 and over , Predictive Value of Tests , Follow-Up Studies , Calcinosis/diagnostic imaging
6.
Arterioscler Thromb Vasc Biol ; 44(8): 1813-1832, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38957984

ABSTRACT

BACKGROUND: Cellular communication among different types of vascular cells is indispensable for maintaining vascular homeostasis and preventing atherosclerosis. However, the biological mechanism involved in cellular communication among these cells and whether this biological mechanism can be used to treat atherosclerosis remain unknown. We hypothesized that endothelial autophagy mediates the cellular communication in vascular tissue through exosome-mediated delivery of atherosclerosis-related genes. METHODS: Rapamycin and adeno-associated virus carrying Atg7 short hairpin RNA under the Tie (TEK receptor tyrosine kinase) promoter were used to activate and inhibit vascular endothelial autophagy in high-fat diet-fed ApoE-/- mice, respectively. miRNA microarray, in vivo and in vitro experiments, and human vascular tissue were used to explore the effects of endothelial autophagy on endothelial function and atherosclerosis and its molecular mechanisms. Quantitative polymerase chain reaction and miRNA sequencing were performed to determine changes in miRNA expression in exosomes. Immunofluorescence and exosome coculture experiments were conducted to examine the role of endothelial autophagy in regulating the communication between endothelial cells and smooth muscle cells (SMCs) via exosomal miRNA. RESULTS: Endothelial autophagy was inhibited in thoracic aortas of high-fat diet-fed ApoE-/- mice. Furthermore, rapamycin alleviated high-fat diet-induced atherosclerotic burden and endothelial dysfunction, while endothelial-specific Atg7 depletion aggravated the atherosclerotic burden. miRNA microarray, in vivo and in vitro experiments, and human vascular tissue analysis revealed that miR-204-5p was significantly increased in endothelial cells after high-fat diet exposure, which directly targeted Bcl2 to regulate endothelial cell apoptosis. Importantly, endothelial autophagy activation decreased excess miR-204-5p by loading miR-204-5p into multivesicular bodies and secreting it through exosomes. Moreover, exosomal miR-204-5p can effectively transport to SMCs, alleviating SMC calcification by regulating target proteins such as RUNX2 (runt-related transcription factor 2). CONCLUSIONS: Our study revealed the exosomal pathway by which endothelial autophagy protects atherosclerosis: endothelial autophagy activation transfers miR-204-5p from endothelial cells to SMCs via exosomes, both preventing endothelial apoptosis and alleviating SMC calcification. REGISTRATION: URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR2200064155.


Subject(s)
Atherosclerosis , Autophagy , Cell Communication , Disease Models, Animal , Exosomes , Mice, Inbred C57BL , Mice, Knockout, ApoE , MicroRNAs , Myocytes, Smooth Muscle , MicroRNAs/metabolism , MicroRNAs/genetics , Exosomes/metabolism , Exosomes/genetics , Animals , Atherosclerosis/pathology , Atherosclerosis/genetics , Atherosclerosis/metabolism , Atherosclerosis/prevention & control , Humans , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/pathology , Male , Mice , Human Umbilical Vein Endothelial Cells/metabolism , Human Umbilical Vein Endothelial Cells/pathology , Endothelial Cells/metabolism , Endothelial Cells/pathology , Autophagy-Related Protein 7/metabolism , Autophagy-Related Protein 7/genetics , Cells, Cultured , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Plaque, Atherosclerotic , Aortic Diseases/pathology , Aortic Diseases/genetics , Aortic Diseases/prevention & control , Aortic Diseases/metabolism , Coculture Techniques , Signal Transduction , Aorta, Thoracic/metabolism , Aorta, Thoracic/pathology , Diet, High-Fat
7.
JACC Cardiovasc Interv ; 17(14): 1680-1690, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39048255

ABSTRACT

BACKGROUND: Thromboembolic events, particularly strokes, remain a major complication of transcatheter aortic valve replacement (TAVR). Embolic protection devices have failed to show significant clinical benefit in large randomized clinical trials. Aortic wall thrombus (AWT) is often observed on multidetector computed tomography during TAVR work-up, but its prognostic significance is uncertain. OBJECTIVES: This study sought to evaluate the association between the presence of AWT and the incidence of thromboembolic outcomes in patients undergoing transfemoral (TF) TAVR for severe aortic stenosis. METHODS: This was a prospective cohort study of consecutive patients who underwent TF TAVR for severe aortic stenosis between January 2011 and April 2022. A dedicated scale (range: 0-10) was qualitatively used to assess AWT. The primary outcome was a composite of procedural thromboembolic events defined as ischemic stroke, blue toe syndrome, bowel ischemia, or other solid organ infarction. The secondary endpoints were ischemic strokes and procedural death. RESULTS: Of the 641 patients included, severe AWT (score ≥8) was identified in 73 (11.4%). The presence of severe AWT was strongly associated with an increase in the primary outcome (OR: 8.48; 95% CI: 3.36-21.40; P < 0.001). This relationship persisted following multivariable analysis, which adjusted for comorbidities and procedural characteristics. The presence of severe AWT was also found to be associated with an increased incidence of stroke and procedural death (OR: 5.66; 95% CI: 2.00-15.30; P = 0.002 and OR: 4.66; 95% CI: 1.80-11.30; P = 0.002, respectively). CONCLUSIONS: The presence of severe AWT on preprocedural multidetector computed tomography is strongly associated with thromboembolic complications including stroke and mortality after TF TAVR.


Subject(s)
Aortic Valve Stenosis , Femoral Artery , Severity of Illness Index , Thromboembolism , Thrombosis , Transcatheter Aortic Valve Replacement , Humans , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/mortality , Transcatheter Aortic Valve Replacement/instrumentation , Female , Male , Aged, 80 and over , Aortic Valve Stenosis/surgery , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/mortality , Prospective Studies , Risk Factors , Aged , Femoral Artery/diagnostic imaging , Thrombosis/diagnostic imaging , Thrombosis/etiology , Thrombosis/mortality , Thrombosis/epidemiology , Treatment Outcome , Thromboembolism/etiology , Thromboembolism/diagnostic imaging , Thromboembolism/mortality , Thromboembolism/prevention & control , Incidence , Risk Assessment , Time Factors , Aortic Valve/surgery , Aortic Valve/diagnostic imaging , Aortic Valve/physiopathology , Multidetector Computed Tomography , Catheterization, Peripheral/adverse effects , Catheterization, Peripheral/mortality , Aortic Diseases/diagnostic imaging , Aortic Diseases/mortality , Punctures
8.
Am J Case Rep ; 25: e944099, 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39069697

ABSTRACT

BACKGROUND Cerebrovascular occlusion is a critical health concern associated with strokes, a leading cause of mortality worldwide. Large vessel occlusion, constituting a significant portion of acute ischemic strokes, presents serious patient outcomes. Occlusions involving multiple extracranial vessels are rare but pose challenges in early detection due to potential absence of overt symptoms. CASE REPORT A 65-year-old man with a significant smoking history and no prior history of hypertension or cardiovascular disease presented with recurrent generalized tonic seizures occurring 4 to 5 times daily. Despite normal neurological examinations, neck sonography indicated potential obstruction in the carotid and vertebral arteries. Conventional angiography revealed mild coronary artery plaques but complete occlusion of all cranial branches originating from the aorta, alongside porcelain aorta. Neck CT angiography confirmed complete occlusion of the supra-aortic branches of the aorta and absence of the right internal carotid artery, with evidence of proximal occlusion of the left internal carotid artery. Medical management without surgical intervention was pursued due to the patient's stable condition. He was discharged with a medication regimen including antiplatelet therapy and statins. Four-month follow-up showed significant symptom improvement, with minimal changes in brain blood flow circulation noted on CT. CONCLUSIONS This case underscores the brain's remarkable adaptive capacity in withstanding severe vascular challenges. The rarity of multiple extracranial vessel occlusions and presence of porcelain aorta further complicated the case. Utilizing advanced imaging techniques and personalized treatment approaches are crucial in managing complex vascular conditions. Ongoing research and careful monitoring are essential to advance understanding and management in such cases.


Subject(s)
Computed Tomography Angiography , Humans , Male , Aged , Aortic Diseases/complications , Aortic Diseases/diagnostic imaging , Arterial Occlusive Diseases/diagnostic imaging
9.
Eur J Cardiothorac Surg ; 65(6)2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38837348

ABSTRACT

OBJECTIVES: To assess the accuracy of a deep learning-based algorithm for fully automated detection of thoracic aortic calcifications in chest computed tomography (CT) with a focus on the aortic clamping zone. METHODS: We retrospectively included 100 chest CT scans from 91 patients who were examined on second- or third-generation dual-source scanners. Subsamples comprised 47 scans with an electrocardiogram-gated aortic angiography and 53 unenhanced scans. A deep learning model performed aortic landmark detection and aorta segmentation to derive 8 vessel segments. Associated calcifications were detected and their volumes measured using a mean-based density thresholding. Algorithm parameters (calcium cluster size threshold, aortic mask dilatation) were varied to determine optimal performance for the upper ascending aorta that encompasses the aortic clamping zone. A binary visual rating served as a reference. Standard estimates of diagnostic accuracy and inter-rater agreement using Cohen's Kappa were calculated. RESULTS: Thoracic aortic calcifications were observed in 74% of patients with a prevalence of 27-70% by aorta segment. Using different parameter combinations, the algorithm provided binary ratings for all scans and segments. The best performing parameter combination for the presence of calcifications in the aortic clamping zone yielded a sensitivity of 93% and a specificity of 82%, with an area under the receiver operating characteristic curve of 0.874. Using these parameters, the inter-rater agreement ranged from κ 0.66 to 0.92 per segment. CONCLUSIONS: Fully automated segmental detection of thoracic aortic calcifications in chest CT performs with high accuracy. This includes the critical preoperative assessment of the aortic clamping zone.


Subject(s)
Aorta, Thoracic , Aortic Diseases , Deep Learning , Tomography, X-Ray Computed , Vascular Calcification , Humans , Aorta, Thoracic/diagnostic imaging , Retrospective Studies , Female , Male , Vascular Calcification/diagnostic imaging , Aged , Middle Aged , Tomography, X-Ray Computed/methods , Aortic Diseases/diagnostic imaging , Algorithms , Aged, 80 and over
10.
Sci Rep ; 14(1): 12656, 2024 06 03.
Article in English | MEDLINE | ID: mdl-38825610

ABSTRACT

This study aimed to investigate the relationship between complex aortic plaque (CAP) and short-term as well as long-term outcomes following cardioembolic stroke. CAP is a known risk factor for occurrence and recurrence of ischemic stroke. However, the association of CAP on cardioembolic stroke remains unclear. This was retrospective study using prospective cohort of consecutive patients with cardioembolic stroke who underwent transesophageal echocardiography. The functional outcome was evaluated using the modified Rankin Scale score at 3 months, and long-term outcomes were assessed by recurrence of ischemic stroke and occurrence of major adverse cardiovascular events (MACE). Among 759 patients with cardioembolic stroke, 91 (12.0%) had CAP. Early ischemic stroke recurrence within 3 months was associated with CAP (p = 0.025), whereas CAP was not associated with functional outcome at 3 months (odd ratio 1.01, 95% confidence interval [CI] 0.57-1.84, p = 0.973). During a median follow-up of 3.02 years, CAP was significantly associated with ischemic stroke recurrence (hazard ratio = 2.68, 95% CI 1.48-4.88, p = 0.001) and MACE occurrence (hazard ratio = 1.61, 95% CI 1.03-2.51, p = 0.039). In conclusion, CAP was associated with early ischemic stroke recurrence and poor long-term outcomes in patients with cardioembolic stroke. It might be helpful to consider transesophageal echocardiography for patients with cardioembolic stroke to identify CAP.


Subject(s)
Embolic Stroke , Ischemic Stroke , Plaque, Atherosclerotic , Humans , Male , Female , Aged , Ischemic Stroke/diagnostic imaging , Ischemic Stroke/etiology , Ischemic Stroke/complications , Plaque, Atherosclerotic/complications , Plaque, Atherosclerotic/diagnostic imaging , Prognosis , Middle Aged , Retrospective Studies , Embolic Stroke/etiology , Echocardiography, Transesophageal , Risk Factors , Recurrence , Aortic Diseases/complications , Aortic Diseases/diagnostic imaging , Prospective Studies , Aged, 80 and over
11.
J Hazard Mater ; 475: 134854, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38889468

ABSTRACT

Microplastics (MPs) have attracted widespread attention because they can lead to combined toxicity by adsorbing heavy metals from the environment. Exposure to lead (Pb), a frequently adsorbed heavy metal by MPs, is common. In the current study, the coexistence of MPs and Pb was assessed in human samples. Then, mice were used as models to examine how co-exposure to MPs and Pb promotes aortic medial degeneration. The results showed that MPs and Pb co-exposure were detected in patients with aortic disease. In mice, MPs and Pb co-exposure promoted the damage of elastic fibers, loss of vascular smooth muscle cells (VSMCs), and release of inflammatory factors. In vitro cell models revealed that co-exposure to MPs and Pb induced excessive reactive oxygen species generation, impaired mitochondrial function, and triggered PANoptosome assembly in VSMCs. These events led to PANoptosis and inflammation through the cAMP/PKA-ROS signaling pathway. However, the use of the PKA activator 8-Br-cAMP or mitochondrial ROS scavenger Mito-TEMPO improved, mitochondrial function in VSMCs, reduced cell death, and inhibited inflammatory factor release. Taken together, the present study provided novel insights into the combined toxicity of MPs and Pb co-exposure on the aorta.


Subject(s)
Lead , Microplastics , Reactive Oxygen Species , Animals , Reactive Oxygen Species/metabolism , Lead/toxicity , Humans , Microplastics/toxicity , Male , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/pathology , Mitochondria/drug effects , Mitochondria/metabolism , Aorta/drug effects , Aorta/pathology , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/pathology , Muscle, Smooth, Vascular/metabolism , Mice, Inbred C57BL , Mice , Female , Middle Aged , Aortic Diseases/chemically induced , Aortic Diseases/pathology , Cyclic AMP-Dependent Protein Kinases/metabolism
12.
Clin Epigenetics ; 16(1): 76, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38845031

ABSTRACT

Tatton-Brown-Rahman syndrome (TBRS) is a rare congenital genetic disorder caused by autosomal dominant pathogenic variants in the DNA methyltransferase DNMT3A gene. Typical TBRS clinical features are overgrowth, intellectual disability, and minor facial anomalies. However, since the syndrome was first described in 2014, a widening spectrum of abnormalities is being described. Cardiovascular abnormalities are less commonly reported but can be a major complication of the syndrome. This article describes a family of three individuals diagnosed with TBRS in adulthood and highlights the variable expression of cardiovascular features. A 34-year-old proband presented with progressive aortic dilatation, mitral valve (MV) regurgitation, left ventricular (LV) dilatation, and ventricular arrhythmias. The affected family members (mother and brother) were diagnosed with MV regurgitation, LV dilatation, and arrhythmias. Exome sequencing and computational protein analysis suggested that the novel familial DNMT3A mutation Ser775Tyr is located in the methyltransferase domain, however, distant from the active site or DNA-binding loops. Nevertheless, this bulky substitution may have a significant effect on DNMT3A protein structure, dynamics, and function. Analysis of peripheral blood cfDNA and transcriptome showed shortened mononucleosome fragments and altered gene expression in a number of genes related to cardiovascular health and of yet undescribed function, including several lncRNAs. This highlights the importance of epigenetic regulation by DNMT3A on cardiovascular system development and function. From the clinical perspective, we suggest that new patients diagnosed with congenital DNMT3A variants and TBRS require close examination and follow-up for aortic dilatation and valvular disease because these conditions can progress rapidly. Moreover, personalized treatments, based on the specific DNMT3A variants and the different pathways of their function loss, can be envisioned in the future.


Subject(s)
DNA (Cytosine-5-)-Methyltransferases , DNA Methyltransferase 3A , Pedigree , Humans , DNA Methyltransferase 3A/genetics , Adult , Male , DNA (Cytosine-5-)-Methyltransferases/genetics , Female , Cardiomyopathies/genetics , Aortic Diseases/genetics , Exome Sequencing/methods , Intellectual Disability/genetics , Mutation
13.
J Feline Med Surg ; 26(6): 1098612X241257878, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38857617

ABSTRACT

PRACTICAL RELEVANCE: Feline aortic thromboembolism (FATE) is commonly encountered in clinical medicine, especially in emergency situations. This often devastating syndrome usually develops secondarily to severe heart disease, and has short- and long-term consequences. CLINICAL FEATURES: The clinical presentation of FATE is consistent with peripheral ischemic neuropathy, usually in both pelvic limbs. Diagnosis is relatively straightforward, but can be assisted with Doppler ultrasound, point-of-care ultrasound or infrared thermal imaging. RECENT ADVANCES AND FUTURE PROSPECTS: Interpretation of survival rates in cats with FATE has been hampered by historically high admission euthanasia, but recent studies suggest a survival rate with supportive care of 30-40%. Moreover, with advances in post-FATE thromboprophylaxis, median survival times of over 1 year are being achieved. Future directions include use of thrombolytic agents and treatment of common FATE sequelae such as acute kidney injury and reperfusion injury. OUTLINE: This article, aimed at small animal veterinarians, including emergency practitioners, reviews key aspects of the clinical presentation, diagnosis and treatment options for FATE, with a view to guiding client and veterinarian decision-making. Three case studies are included to illustrate the practical application of information presented in the review. EVIDENCE BASE: There are limited prospective studies on FATE, although the recent literature reflects a resurgence in clinical research interest in the past few years. Advances in FATE treatment will benefit many cats and it is important that research efforts continue to identify appropriate treatment modalities.


Subject(s)
Aortic Diseases , Cat Diseases , Thromboembolism , Cats , Cat Diseases/diagnosis , Cat Diseases/therapy , Animals , Aortic Diseases/veterinary , Aortic Diseases/diagnosis , Thromboembolism/veterinary , Thromboembolism/prevention & control , Female , Male
14.
Medicine (Baltimore) ; 103(24): e38608, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38875360

ABSTRACT

Waist-to-height ratio (WtHR) is a validated biomarker of central obesity that appears to be preferable to other body composition measurements in the evaluation of cardiovascular disease. The goal of this research was to explore the connection between WtHR and abdominal aortic calcification (AAC) among adults. On the basis of data from the 2013 to 2014 National Health and Nutrition Examination Survey, multivariate logistic regression, sensitivity analysis, as well as smoothed curve fitting were used to evaluate the connection between WtHR and AAC. Subgroup analyses along with interaction tests were done to see if this link was consistent across populations. Among 3079 participants aged >40 years, there was a negative association between WtHR and ACC. Each 1-unit emergence of WtHR was related to a 2% reduction in the probability of severe AAC in the entirely adjusted model (odds ratio = 0.02, 95% confidence interval: [0.00-0.12]). Participants in the highest WtHR quartile were 39% less likely to acquire severe AAC compared with those in the lowest quartile. (odds ratio = 0.61, 95% confidence interval: [0.37-1.00]). This negative association was more pronounced in the diabetes subgroup. We discovered a reversed U-shaped association between WtHR as well as AAC score utilizing a 2-stage linear regression model, with an intersection point of 0.56. WtHR was negatively associated with AAC among US adults.


Subject(s)
Aorta, Abdominal , Nutrition Surveys , Vascular Calcification , Waist-Height Ratio , Humans , Cross-Sectional Studies , Male , Aorta, Abdominal/diagnostic imaging , Aorta, Abdominal/pathology , Middle Aged , Female , Vascular Calcification/epidemiology , Vascular Calcification/diagnostic imaging , Adult , Aortic Diseases/epidemiology , Aortic Diseases/diagnostic imaging , Aged , Risk Factors , Obesity, Abdominal/epidemiology
15.
Vasa ; 53(4): 255-262, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38874211

ABSTRACT

Background: The clinical outcomes and survival of patients with penetrating aortic ulcers (PAU) were evaluated in a tertiary care hospital, comparing those who underwent aortic repair to those treated conservatively. Patients and methods: A retrospective single-centre analysis included all patients that underwent a computed tomography angiography (CT-A) scan with the diagnosis of a PAU between January 2009 and May 2019. "PAU" was identified in 1,493 of 112,506 CT-A scan reports in 576 patients. Clinical and angiomorphological data were collected. The primary outcome was overall survival (OS), with secondary outcomes focusing on identifying risk factors for poor OS. Survival probabilities were analysed by the Kaplan-Meier method using the log-rank test. A Cox hazard model using survival as dependent variable with stepwise backward eliminations based on the likelihood ratios was employed. Results: 315 PAUs were identified in 278 patients. The prevalence in the cohort was 0.8%. The mean age of the patients was 74.4 years, and they were predominantly male (n = 208, 74.8%). The mean ulcer depth was 11.8 mm (range 2-50 mm). Out of the patients, 232 were asymptomatic (83.5%). Among 178 PAUs (56.5%), high-risk factors, such as ulcer depth >10 mm, aortic diameter >40 mm, and ulcer length >20 mm, were observed. Aortic repair was associated with a better mean OS compared to conservatively managed patients (72.6 versus 32.2 months, p = 0.001). The Cox hazard model showed that ulcer depth >1 mm was associated with poor OS (HR 0.67, p = 0.048), while aortic repair was related to a better OS (HR 4.365, p<0.013). Conclusions: Aortic repair is associated with better OS, but this finding should be interpreted with caution because of differences in age and comorbidities between the groups. Further evaluation is warranted through prospective studies with randomized groups. Further assessment for angiomorphological parameters is recommended to identify patients at increased risk for poor OS.


Subject(s)
Aortic Diseases , Computed Tomography Angiography , Conservative Treatment , Ulcer , Humans , Male , Female , Ulcer/mortality , Ulcer/diagnostic imaging , Ulcer/therapy , Ulcer/surgery , Retrospective Studies , Conservative Treatment/adverse effects , Conservative Treatment/mortality , Aged , Risk Factors , Treatment Outcome , Time Factors , Aortic Diseases/mortality , Aortic Diseases/diagnostic imaging , Aortic Diseases/therapy , Aortic Diseases/surgery , Middle Aged , Aged, 80 and over , Risk Assessment , Blood Vessel Prosthesis Implantation/mortality , Blood Vessel Prosthesis Implantation/adverse effects , Aortography , Endovascular Procedures/adverse effects , Endovascular Procedures/mortality , Penetrating Atherosclerotic Ulcer
16.
Arterioscler Thromb Vasc Biol ; 44(8): 1852-1872, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38868941

ABSTRACT

BACKGROUND: Atherosclerosis is driven by the infiltration of the arterial intima by diverse immune cells and smooth muscle cells (SMCs). CD8+ T cells promote lesion growth during atherosclerotic lesion development, but their role in advanced atherosclerosis is less clear. Here, we studied the role of CD8+ T cells and their effects on SMCs in established atherosclerosis. METHODS: CD8+ T cells were depleted in (SMC reporter) low-density lipoprotein receptor-deficient (Ldlr-/-) mice with established atherosclerotic lesions. Atherosclerotic lesion formation was examined, and single-cell RNA sequencing of aortic SMCs and their progeny was performed. Additionally, coculture experiments with primary aortic SMCs and CD8+ T cells were conducted. RESULTS: Although we could not detect differences in atherosclerotic lesion size, an increased plaque SMC content was noted in mice after CD8+ T-cell depletion. Single-cell RNA sequencing of aortic lineage-traced SMCs revealed contractile SMCs and a modulated SMC cluster, expressing macrophage- and osteoblast-related genes. CD8+ T-cell depletion was associated with an increased contractile but decreased macrophage and osteoblast-like gene signature in this modulated aortic SMC cluster. Conversely, exposure of isolated aortic SMCs to activated CD8+ T cells decreased the expression of genes indicative of a contractile SMC phenotype and induced a macrophage and osteoblast-like cell state. Notably, CD8+ T cells triggered calcium deposits in SMCs under osteogenic conditions. Mechanistically, we identified transcription factors highly expressed in modulated SMCs, including Runx1, to be induced by CD8+ T cells in cultured SMCs in an IFNγ (interferon-γ)-dependent manner. CONCLUSIONS: We here uncovered CD8+ T cells to control the SMC phenotype in atherosclerosis. CD8+ T cells promote SMC dedifferentiation and drive SMCs to adopt features of macrophage-like and osteoblast-like, procalcifying cell phenotypes. Given the critical role of SMCs in atherosclerotic plaque stability, CD8+ T cells could thus be explored as therapeutic target cells during lesion progression.


Subject(s)
Atherosclerosis , CD8-Positive T-Lymphocytes , Cell Dedifferentiation , Disease Models, Animal , Muscle, Smooth, Vascular , Myocytes, Smooth Muscle , Plaque, Atherosclerotic , Animals , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Myocytes, Smooth Muscle/pathology , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/immunology , Mice , Atherosclerosis/pathology , Atherosclerosis/metabolism , Atherosclerosis/genetics , Atherosclerosis/immunology , Muscle, Smooth, Vascular/pathology , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/immunology , Mice, Inbred C57BL , Mice, Knockout , Cells, Cultured , Male , Receptors, LDL/genetics , Receptors, LDL/deficiency , Phenotype , Core Binding Factor Alpha 2 Subunit/genetics , Core Binding Factor Alpha 2 Subunit/metabolism , Aorta/pathology , Aorta/immunology , Aorta/metabolism , Coculture Techniques , Aortic Diseases/pathology , Aortic Diseases/genetics , Aortic Diseases/immunology , Aortic Diseases/metabolism
17.
J Med Case Rep ; 18(1): 285, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38902817

ABSTRACT

BACKGROUND: An aortoesophageal fistula can prove to be fatal. Salvage thoracic endovascular aortic repair as a bridging therapy and radical surgery with thoracotomy should be considered while treating aortoesophageal fistula without spontaneous closure. Moreover, it is essential to select a technique that reduces the risk of reinfection. Here we report a rare case of a ruptured thoracic aortic aneurysm related to esophageal perforation by a fish bone that led to massive hematemesis and shock, and the surgical treatment of an aortoesophageal fistula that developed after salvage thoracic endovascular aortic repair. CASE PRESENTATION: A 70-year-old Japanese female patient was admitted with hematemesis, thoracic pain, and shock related to esophageal perforation of a ruptured descending aortic aneurysm caused by fish bone aspiration and esophageal perforation 1 month previously. An emergency thoracic endovascular aortic repair was performed. Postoperatively, an aortoesophageal fistula that remained open and a food intake-related increase in the inflammatory response was noted. Radical blood-vessel prosthesis implantation and fistula closure were performed. The patient's postoperative course was favorable and the patient was discharged 22 days after the blood vessel prosthesis implantation. CONCLUSION: Such a case of rupture of a descending aortic aneurysm related to perforation by a fish bone and an aortoesophageal fistula is considerably rare. Thus, we report the therapeutic strategy of this particular case and review the relevant literature.


Subject(s)
Aortic Aneurysm, Thoracic , Aortic Rupture , Endovascular Procedures , Esophageal Fistula , Esophageal Perforation , Humans , Female , Esophageal Fistula/surgery , Esophageal Fistula/etiology , Aged , Endovascular Procedures/methods , Aortic Aneurysm, Thoracic/surgery , Aortic Rupture/surgery , Esophageal Perforation/surgery , Esophageal Perforation/etiology , Vascular Fistula/surgery , Vascular Fistula/etiology , Blood Vessel Prosthesis Implantation , Salvage Therapy/methods , Animals , Hematemesis/etiology , Aortic Diseases/surgery , Aortic Diseases/etiology , Aorta, Thoracic/surgery , Treatment Outcome , Fishes , Endovascular Aneurysm Repair
18.
J Vasc Surg ; 79(3): 514-525, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38941265

ABSTRACT

OBJECTIVE: The outcomes of the best medical treatment (BMT) and intervention treatment (INT) in a single-center experience were reported in type B intramural hematoma (IMH). METHODS: From February 2015 to February 2021, a total of 195 consecutive patients with type B IMH were enrolled in the study. The primary end point was mortality, and the secondary end points included clinical and imaging outcomes. The clinical outcomes were aortic-related death, retrograde type A aortic dissection, stent graft-induced new entry tear, endoleak, and reintervention. The imaging outcome was evaluated through the latest follow-up computed tomography angiography, which included aortic rupture, aortic dissection, aortic aneurysm, rapid growth of aortic diameter, newly developed or enlarged penetrating aortic ulcer or ulcer-like projection (ULP) and increased aortic wall thickness. Kaplan-Meier curves were used to assess the association between different treatments. RESULTS: Among the enrolled patients, 115 received BMT, and 80 received INT. There was no significant difference in early (1.7% vs 2.5%; P = 1.00) and midterm all-cause death (8.3% vs 5.2%; P = .42) between the BMT and INT groups. However, patients who underwent INT were at risk of procedure-related complications such as stent graft-induced new entry tear and endoleaks. The INT group was associated with a profound decrease in the risk of ULP, including newly developed ULP (4.3% vs 26.9%; P < .05), ULP enlargement (6.4% vs 31.3%; P < .05), and a lower proportion of high-risk ULP (10.9% vs 45.6%; P < .05). Although there was no significant difference in the incidence of IMH regression between the two groups, the maximum diameter of the descending aorta in patients receiving INT was larger compared with those treated with BMT. CONCLUSIONS: Based on our limited experience, patients with type B IMH treated with BMT or INT shared similar midterm clinical outcome. Patients who underwent INT may have a decreased risk of ULPs, but a higher risk of procedure-related events and patients on BMT should be closely monitored for ULP progression.


Subject(s)
Blood Vessel Prosthesis Implantation , Endovascular Procedures , Hematoma , Humans , Male , Female , Hematoma/diagnostic imaging , Hematoma/etiology , Hematoma/therapy , Aged , Middle Aged , Retrospective Studies , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/mortality , Treatment Outcome , Endovascular Procedures/adverse effects , Endovascular Procedures/mortality , Endovascular Procedures/instrumentation , Risk Factors , Time Factors , Stents , Computed Tomography Angiography , Aortic Diseases/diagnostic imaging , Aortic Diseases/mortality , Aortic Diseases/therapy , Aortic Dissection/diagnostic imaging , Aortic Dissection/mortality , Aortic Dissection/surgery , Aortic Dissection/therapy , Risk Assessment , Postoperative Complications/etiology , Blood Vessel Prosthesis , Aortic Intramural Hematoma
19.
Am J Vet Res ; 85(8)2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38925144

ABSTRACT

OBJECTIVE: To demonstrate hypercoagulability with a benchtop viscoelastic monitor in cats with congestive heart failure (CHF) and/or aortic thromboembolism (ATE) compared to controls. METHODS: 97 cats were enrolled throughout this prospective observational cohort study from September 2022 through October 2023. Cats were grouped by diagnosis of CHF, ATE, ATE plus CHF, or controls. Enrollment required diagnosis of heart disease and no previous antithrombotic therapy. The results of viscoelastic testing with the benchtop viscoelastic coagulation monitor (VCM Vet [VCM]; Entegrion) were compared between groups using factorial analysis of variance. RESULTS: Cats with heart disease had significantly higher clot times when compared to controls (control: mean, 285.3 [SD, 172.6]; CHF: mean, 391.7 [SD, 106.8]; ATE: mean, 415.9 [SD, 109.2]; and ATE plus CHF: mean, 368.6 [SD, 232.6]). Heart disease cats were noted to have significantly lower 45-minute lysis index values (control: median, 100 [range, 93 to 100]; CHF: median, 99 [range, 89 to 100]; ATE: median, 98 [range, 88 to 100]; and ATE plus CHF: range, 98 [91 to 100]). Age was a covariate to this variable, and when applied to analysis, statistical significance was lost. No significant difference in any other variables were noted. CLINICAL RELEVANCE: The hypercoagulability of ATE and CHF cats was not detected by the VCM. Further research with other coagulation monitors is required in this population.


Subject(s)
Cat Diseases , Heart Failure , Thromboembolism , Thrombophilia , Animals , Cats , Cat Diseases/blood , Heart Failure/veterinary , Heart Failure/blood , Thrombophilia/veterinary , Thrombophilia/blood , Male , Female , Prospective Studies , Thromboembolism/veterinary , Thromboembolism/blood , Aortic Diseases/veterinary , Aortic Diseases/blood , Cohort Studies
20.
J Cardiovasc Pharmacol ; 84(1): 45-57, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38922585

ABSTRACT

ABSTRACT: Atherosclerosis (AS) is a chronic progressive disease caused by various factors and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the plasma levels of low-density lipoprotein cholesterol is the primary goal in preventing and treating AS. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in regulating low-density lipoprotein cholesterol metabolism. Panax notoginseng has potent lipid-reducing effects and protects against CVDs, and its saponins induce vascular dilatation, inhibit thrombus formation, and are used in treating CVDs. However, the anti-AS effect of the secondary metabolite, 20( S )-protopanaxatriol (20( S )-PPT), remains unclear. In this study, the anti-AS effect and molecular mechanism of 20( S )-PPT were investigated in vivo and in vitro by Western blotting, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence staining, and other assays. The in vitro experiments revealed that 20( S )-PPT reduced the levels of PCSK9 in the supernatant of HepG2 cells, upregulated low-density lipoprotein receptor protein levels, promoted low-density lipoprotein uptake by HepG2 cells, and reduced PCSK9 mRNA transcription by upregulating the levels of forkhead box O3 protein and mRNA and decreasing the levels of HNF1α and SREBP2 protein and mRNA. The in vivo experiments revealed that 20( S )-PPT upregulated aortic α-smooth muscle actin expression, increased the stability of atherosclerotic plaques, and reduced aortic plaque formation induced by a high-cholesterol diet in ApoE -/- mice (high-cholesterol diet-fed group). Additionally, 20( S )-PPT reduced the aortic expression of CD68, reduced inflammation in the aortic root, and alleviated the hepatic lesions in the high-cholesterol diet-fed group. The study revealed that 20( S )-PPT inhibited low-density lipoprotein receptor degradation via PCSK9 to alleviate AS.


Subject(s)
Aorta , Aortic Diseases , Atherosclerosis , Disease Models, Animal , Mice, Inbred C57BL , Mice, Knockout, ApoE , Plaque, Atherosclerotic , Proprotein Convertase 9 , Receptors, LDL , Sapogenins , Animals , Atherosclerosis/metabolism , Atherosclerosis/pathology , Atherosclerosis/drug therapy , Atherosclerosis/prevention & control , Atherosclerosis/genetics , Sapogenins/pharmacology , Proprotein Convertase 9/metabolism , Proprotein Convertase 9/genetics , Receptors, LDL/genetics , Receptors, LDL/metabolism , Humans , Male , Aortic Diseases/pathology , Aortic Diseases/prevention & control , Aortic Diseases/metabolism , Aortic Diseases/genetics , Aortic Diseases/drug therapy , Aorta/drug effects , Aorta/metabolism , Aorta/pathology , Proteolysis/drug effects , Hep G2 Cells , PCSK9 Inhibitors , Signal Transduction/drug effects , Sterol Regulatory Element Binding Protein 2/metabolism , Sterol Regulatory Element Binding Protein 2/genetics , Mice , Diet, High-Fat , Apolipoproteins E
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