RESUMEN
Abdominal aortic aneurysm (AAA) is a life-threatening disease associated with high mortality rates. It is characterized by the permanent dilation of the abdominal aorta with at least a 50% increase in arterial diameter. Various animal models of AAA have been introduced to mimic the pathophysiological changes and study the underlying mechanisms of AAA. Among these models, the calcium chloride (CaCl2)- and elastase-induced AAA models are commonly used in mice. However, these methods have certain limitations. Traditional intraluminal porcine pancreatic elastase (PPE) perfusion is associated with high technical difficulty and a high rupture rate, while periadventitial administration of PPE yields inconsistent results. In addition, the CaCl2-induced AAA model lacks human AAA features, such as atherothrombosis and aneurysm rupture. Therefore, the combined application of CaCl2 and PPE has been proposed as an approach to enhance success rates and induce greater diameter increases in AAA animal models. This manuscript presents a comprehensive protocol for establishing a mouse AAA model through periaortic infiltration of PPE and CaCl2 in the infrarenal segment of the abdominal aorta. By following this protocol, we can achieve an AAA formation rate of approximately 90% with technical simplicity and reproducibility. Further ultrasound and histological experiments confirm that this model effectively replicates the morphological and pathological changes observed in human AAA.
Asunto(s)
Aneurisma de la Aorta Abdominal , Cloruro de Calcio , Modelos Animales de Enfermedad , Elastasa Pancreática , Aneurisma de la Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/inducido químicamente , Animales , Ratones , Aorta Abdominal/patología , Masculino , Ratones Endogámicos C57BL , PorcinosRESUMEN
OBJECTIVES: Intimal tears caused by aortic dissection can weaken the arterial wall and lead to aortic aneurysms. However, the effect of different tear states on the blood flow behaviour remains complex. This study uses a novel approach that combines numerical haemodynamic simulation with in vitro experiments to elucidate the effect of arterial dissection rupture on the complex blood flow state within the abdominal aneurysm and the endogenous causes of end-organ malperfusion. MATERIALS AND METHODS: Based on the CT imaging data and clinical physiological parameters, the overall arterial models including aortic dissection and aneurysm with single tear and double tear were established, and the turbulence behaviours and haemodynamic characteristics of arterial dissection and aneurysm under different blood pressures were simulated by using non-Newtonian flow fluids with the pulsatile blood flow rate of the clinical patients as a cycle, and the results of the numerical simulation were verified by in vitro simulation experiments. RESULTS: Hemodynamic simulations revealed that the aneurysm and single-tear false lumen generated a maximum pressure of 320.591 mmHg, 267 % over the 120 mmHg criterion. The pressure differential generates reflux, leading to a WSS of 2247.9 Pa at the TL inlet and blood flow velocities of up to 6.41 m/s inducing extend of the inlet. DTD Medium FL instantaneous WP above 120 mmHg Standard 151 % Additionally, there was 82.5 % higher flow in the right iliac aorta than in the left iliac aorta, which triggered malperfusion. Thrombus was accumulated distal to the tear and turbulence. These results are consistent with the findings of the in vitro experiments. CONCLUSIONS: This study reveals the haemodynamic mechanisms by which aortic dissection induces aortic aneurysms to produce different risk states. This will contribute to in vitro simulation studies as a new fulcrum in the process of moving from numerical simulation to clinical trials.
Asunto(s)
Aorta Abdominal , Hemodinámica , Humanos , Aorta Abdominal/fisiopatología , Aorta Abdominal/diagnóstico por imagen , Rotura de la Aorta/fisiopatología , Rotura de la Aorta/diagnóstico por imagen , Disección Aórtica/fisiopatología , Disección Aórtica/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/fisiopatología , Modelos CardiovascularesRESUMEN
Arterial stiffness, a key indicator of vascular health, encompassing active (vascular tone) and passive (extracellular matrix) components. This study aims to address how these different components affect arterial stiffness along the aorta and the influence of aging. Aortic segments of 12 week and 24 month old (both n = 6) male C57BL/6J mice were mounted in a Rodent Oscillatory Set-up to study Arterial Compliance, in order to measure arterial stiffness and vascular reactivity. Regional variations in arterial stiffness were evident, with abdominal infrarenal aorta (AIA) exhibiting highest stiffness and smallest diameters. AIA displayed both the highest amount of collagen and collagen:elastin ratio. Regional ex vivo vascular reactivity revealed heightened AIA contractions and lowered NO availability. Aging is a significant factor contributing towards vessel remodelling and arterial stiffness. Aging increased arterial stiffness, aortic diameters, collagen content, and reduced VSMC contraction. The results of this study could identify specific regions or mechanisms to target in the development of innovative therapeutic interventions aimed at enhancing overall vascular health.
Asunto(s)
Envejecimiento , Colágeno , Ratones Endogámicos C57BL , Rigidez Vascular , Animales , Rigidez Vascular/fisiología , Masculino , Envejecimiento/fisiología , Ratones , Colágeno/metabolismo , Elastina/metabolismo , Matriz Extracelular/metabolismo , Aorta/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiología , Aorta Abdominal/metabolismo , Aorta Abdominal/fisiopatologíaRESUMEN
A Gravida 2 Para 1 Live 1 in her late 20s and of South Asian ethnicity with previous lower segment caesarean section (LSCS) was hospitalised for confinement at 37 weeks for chronic hypertension with superimposed pre-eclampsia.The patient was diagnosed with type III Takayasu's arteritis following a previous uncomplicated pregnancy. A year after her first childbirth, she presented with headache, recurrent scleritis, hypertension, bilateral absent lower limb pulses and right femoral bruit. CT angiogram revealed concentric thickening of the aorta and complete occlusion of the infrarenal aorta, with a saccular aneurysm 18 mm in diameter in the distal thoracic aorta at the T10 level. She was started on immunosuppressants and antihypertensives. During the current pregnancy, she received multidisciplinary care and underwent an elective LSCS with intrauterine contraceptive device (IUCD) placement at term under spinal anaesthesia. Postoperatively, nitroglycerine infusion followed by oral labetalol was administered for hypertension. She was discharged on day 10 with regular follow-up.
Asunto(s)
Complicaciones Cardiovasculares del Embarazo , Arteritis de Takayasu , Humanos , Arteritis de Takayasu/complicaciones , Arteritis de Takayasu/tratamiento farmacológico , Arteritis de Takayasu/diagnóstico , Femenino , Embarazo , Adulto , Complicaciones Cardiovasculares del Embarazo/terapia , Complicaciones Cardiovasculares del Embarazo/diagnóstico , Cesárea , Antihipertensivos/uso terapéutico , Aorta Abdominal/diagnóstico por imagen , Angiografía por Tomografía ComputarizadaRESUMEN
Aneurysms of the abdominal aorta are only sporadically documented in the veterinary literature. This publication describes 2 canine cases in which abdominal aortic malformation was detected by sonography and confirmed by computed tomography. In one case a histological diagnosis of an aortic aneurysm was possible.One dog showed posterior weakness, in the second dog the aortic aneurysm had been noticed sonographically during a routine examination.In the patient with the proven aortic aneurysm, it may be presumed that a hemodynamically relevant component in consequence to the altered flow profile and occurring turbulence exists. In accordance with human medical standards, regular monitoring of these patients, both clinically and by ultrasound, would therefore appear to be useful in order to be able to detect the occurrence or progression of secondary hemodynamic changes and possible thrombus formation at an early stage. In contrast, the second case presented here has not shown any clinical signs with regard to the abdominal vascular malformation up to the present time.
Asunto(s)
Aorta Abdominal , Aneurisma de la Aorta Abdominal , Enfermedades de los Perros , Perros , Animales , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/congénito , Aorta Abdominal/anomalías , Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/veterinaria , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/diagnóstico , Ultrasonografía/veterinaria , Tomografía Computarizada por Rayos X/veterinaria , Masculino , FemeninoRESUMEN
BACKGROUND: Intimal hyperplasia is a normal adaptive feature of arteries in response to injuries, which include invasive vascular interventions. Its development limits the long-term success of bypass grafts. Various pharmacological agents have been successfully employed in experimental models to reduce the degree of intimal hyperplasia. In our study, we investigated the efficacy of dexamethasone in reducing intimal hyperplasia in rat abdominal aortas after partial transection and primary repair. METHODS: In this study, 20 Wistar Albino rats were randomly selected and divided into four groups to compare the effects of low- and high-dose dexamethasone on intima and media thickness compared to the control. Group A (n=5) was the control group, where only skin incision and laparotomy were performed. For Group B (n=5), a median laparotomy was performed, the abdominal aorta was partially transected, and repaired with an 8.0 prolene suture. Doses of 0.1 mg/kg and 0.2 mg/kg dexamethasone were administered in Group C (n=5) and Group D (n=5), respectively. After two weeks, all rats were euthanized, and the repaired abdominal aortas were excised and examined histopathologically. Intima and media thicknesses were measured using the 'Olympus AnalySIS 5' program (Olympus Corporation, Japan) after digital photos were taken. RESULTS: Based on the measurements, we demonstrated that after transection and repair of the abdominal aorta, the intima/media ratio was not significantly different between the low-dose dexamethasone and non-dexamethasone groups. The intima/media ratio was significantly lower in the high-dose dexamethasone group than in the non-dexamethasone and low-dose dexamethasone groups. CONCLUSION: After vascular interventions, dexamethasone treatment may reduce intimal hyperplasia and increase patency by providing vascular remodeling.
Asunto(s)
Aorta Abdominal , Dexametasona , Hiperplasia , Ratas Wistar , Túnica Íntima , Animales , Dexametasona/farmacología , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Aorta Abdominal/cirugía , Aorta Abdominal/patología , Ratas , Hiperplasia/tratamiento farmacológico , Hiperplasia/patología , Hiperplasia/prevención & control , Túnica Íntima/patología , Túnica Íntima/efectos de los fármacos , Modelos Animales de Enfermedad , MasculinoRESUMEN
Blood flow through the abdominal aorta and iliac arteries is a crucial area of research in hemodynamics and cardiovascular diseases. To get in to the problem, this study presents detailed analyses of blood flow through the abdominal aorta, together with left and right iliac arteries, under Earth gravity and weightless conditions, both at the rest stage, and during physical activity. The analysis were conducted using ANSYS Fluent software. The results indicate, that there is significantly less variation in blood flow velocity under weightless conditions, compared to measurement taken under Earth Gravity conditions. Study presents, that the maximum and minimum blood flow velocities decrease and increase, respectively, under weightless conditions. Our model for the left iliac artery revealed higher blood flow velocities during the peak of the systolic phase (systole) and lower velocities during the early diastolic phase (diastole). Furthermore, we analyzed the shear stress of the vessel wall and the mean shear stress over time. Additionally, the distribution of oscillatory shear rate, commonly used in hemodynamic analyses, was examined to assess the effects of blood flow on the blood vessels. Countermeasures to mitigate the negative effects of weightlessness on astronauts health are discussed, including exercises performed on the equipment aboard the space station. These exercises aim to maintain optimal blood flow, prevent the formation of atherosclerotic plaques, and reduce the risk of cardiovascular complications.
Asunto(s)
Aorta Abdominal , Ingravidez , Humanos , Aorta Abdominal/fisiología , Velocidad del Flujo Sanguíneo/fisiología , Hemodinámica/fisiología , Arteria Ilíaca , Modelos Cardiovasculares , Planeta Tierra , Simulación de IngravidezRESUMEN
Besides sepsis and malignancy, malperfusion is the third leading cause of tissue degradation and a major pathomechanism for various medical and surgical conditions. Despite significant developments such as bypass surgery, endovascular procedures, extracorporeal membrane oxygenation, and artificial blood substitutes, tissue malperfusion, especially of visceral organs, remains a pressing issue in patient care. The demand for further research on biomedical processes and possible interventions is high. Valid biological models are of utmost importance in enabling this kind of research. Due to the multifactorial aspects of tissue perfusion research, which include not only cell biology but also vascular microanatomy and rheology, an appropriate model requires a degree of biological complexity that only an animal model can provide, rendering rodents the obvious model of choice. Tissue malperfusion can be differentiated into three distinct conditions: (1) isolated arterial ischemia, (2) isolated venous congestion, and (3) combined malperfusion. This article presents a detailed step-by-step protocol for the controlled and reversible induction of these three types of visceral malperfusion via midline laparotomy and clamping of the abdominal aorta and caval vein in rats, underscoring the significance of precise surgical methodology to guarantee uniform and dependable results. Prime examples of possible applications of this model include the development and validation of innovative intraoperative imaging modalities, such as Hyperspectral Imaging (HSI), to objectively visualize and differentiate malperfusion of gastrointestinal, gynecological, and urological organs.
Asunto(s)
Isquemia , Laparotomía , Animales , Ratas , Laparotomía/métodos , Isquemia/cirugía , Vísceras/irrigación sanguínea , Vísceras/cirugía , Aorta Abdominal/cirugía , Masculino , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: Personalized modeling is a promising tool to improve abdominal aortic aneurysm (AAA) rupture risk assessment. Computed tomography (CT) and quantitative flow (Q-flow) magnetic resonance imaging (MRI) are widely regarded as the gold standard for acquiring patient-specific geometry and velocity profiles, respectively. However, their frequent utilization is hindered by various drawbacks. Ultrasound is used extensively in current clinical practice and offers a safe, rapid and cost-effective method to acquire patient-specific geometries and velocity profiles. This study aims to extract and validate patient-specific velocity profiles from Doppler ultrasound and to examine the impact of the velocity profiles on computed hemodynamics. METHODS: Pulsed-wave Doppler (PWD) and color Doppler (CD) data were successfully obtained for six volunteers and seven patients and employed to extract the flow pulse and velocity profile over the cross-section, respectively. The US flow pulses and velocity profiles as well as generic Womersley profiles were compared to the MRI velocities and flows. Additionally, CFD simulations were performed to examine the combined impact of the velocity profile and flow pulse. RESULTS: Large discrepancies were found between the US and MRI velocity profiles over the cross-sections, with differences for US in the same range as for the Womersley profile. Differences in flow pulses revealed that US generally performs best in terms of maximum flow, forward flow and ratios between forward and backward flow, whereas it often overestimates the backward flow. Both spatial patterns and magnitude of the computed hemodynamics were considerably affected by the prescribed velocity boundary conditions. Larger errors and smaller differences between the US and generic CFD cases were observed for patients compared to volunteers. CONCLUSION: These results show that it is feasible to acquire the patient-specific flow pulse from PWD data, provided that the PWD acquisition could be performed proximal to the aneurysm region, and resulted in a triphasic flow pattern. However, obtaining the patient-specific velocity profile over the cross-section using CD data is not reliable. For the volunteers, utilizing the US flow profile instead of the generic flow profile generally resulted in improved performance, whereas this was the case in more than half of the cases for the patients.
Asunto(s)
Aorta Abdominal , Estudios de Factibilidad , Hemodinámica , Ultrasonografía Doppler , Humanos , Aorta Abdominal/diagnóstico por imagen , Aorta Abdominal/fisiopatología , Masculino , Anciano , Femenino , Adulto , Modelos Cardiovasculares , Persona de Mediana Edad , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/fisiopatología , Imagen por Resonancia Magnética , Modelación Específica para el Paciente , Velocidad del Flujo SanguíneoRESUMEN
Here, we describe an interesting case of a patient with the duplication of inferior vena cava, high-positioned bifurcation of the abdominal aorta with transposition of iliac arteries, and right renal aplasia associated with end-stage renal disease who underwent kidney transplant. In this case, the patient with anorectal malformations with a vaginal fistula was prepared and underwent a kidney transplant. During the surgery, we discovered duplicated inferior vena cava and transposed iliac arteries. After the surgery, computed tomography angiography revealed the inferior vena cava duplication with the 2 connections between the right and left inferior vena cava with the formation of an anomalous circle, high-positioned bifurcation of the abdominal aorta at the level of the L2 vertebral body, and transposition of right and left iliac arteries. Also, we observed the right kidney aplasia and absence of blood circulation in the left native kidney. In our case, a delayed diagnosis of pyelonephritis resulted in the progression to end-stage renal disease that necessitated a kidney transplant, during which we found these anomalies. We confirmed the asymptomatic course of these anomalies, diagnosed only during radiological imaging or surgical intervention. Patients with congenital anomalies of the kidney and urinary tract should undergo complete investigations before surgical decisions. Diagnosis of this pathology in the preoperative period, especially in transplant patients, will alert the surgery team in advance of the operation and allow preparation for the intraoperative difficulties that are typically associated with anomalies such as inferior vena cava transposition or aplasia.
Asunto(s)
Aorta Abdominal , Fallo Renal Crónico , Trasplante de Riñón , Malformaciones Vasculares , Vena Cava Inferior , Humanos , Vena Cava Inferior/anomalías , Vena Cava Inferior/diagnóstico por imagen , Vena Cava Inferior/cirugía , Femenino , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/etiología , Fallo Renal Crónico/diagnóstico , Resultado del Tratamiento , Aorta Abdominal/anomalías , Aorta Abdominal/cirugía , Aorta Abdominal/diagnóstico por imagen , Malformaciones Vasculares/cirugía , Malformaciones Vasculares/complicaciones , Malformaciones Vasculares/diagnóstico por imagen , Aortografía , Angiografía por Tomografía Computarizada , Anomalías Múltiples/cirugía , Flebografía/métodos , Hallazgos Incidentales , Arteria Ilíaca/cirugía , Arteria Ilíaca/anomalías , Arteria Ilíaca/diagnóstico por imagen , Adulto , Pielonefritis/cirugía , Pielonefritis/etiología , Pielonefritis/diagnóstico , Pielonefritis/diagnóstico por imagen , Valor Predictivo de las PruebasRESUMEN
There is a pressing need for alternative medical treatments for abdominal aortic aneurysms (AAAs). Mesenchymal regenerative cells derived from adipose tissue (ADRCs) have shown potential in modulating the inflammation and immune responses that drive AAA progression. We hypothesized that ADRCs could reduce inflammation and preserve vascular integrity, potentially slowing the progression of AAA. In our study, subcutaneous adipose tissue was harvested from male Sprague Dawley rats, from which ADRCs were isolated. AAA was induced in these rats using intraluminal porcine pancreatic elastase, followed by intravenous administration of either ADRCs (106 cells) or saline (0.1 mL). We monitored the progression of AAA through weekly ultrasound, and the rats were sacrificed on day 28 for histological analysis. Our results showed no significant difference in the inner abdominal aortic diameter at day 28 between the control group (172% ± 73%, n = 17) and the ADRC-treated group (181% ± 75%, n = 15). Histological analyses of AAA cross-sections also revealed no significant difference in the infiltration of neutrophils or macrophages between the two groups. Furthermore, the integrity and content of elastin in the tunica media were similar between groups. These findings indicate that a single injection of ADRCs does not inhibit the development of AAA in rats in a randomized blinded study.
Asunto(s)
Tejido Adiposo , Aneurisma de la Aorta Abdominal , Ratas Sprague-Dawley , Animales , Aneurisma de la Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/prevención & control , Aneurisma de la Aorta Abdominal/metabolismo , Ratas , Masculino , Modelos Animales de Enfermedad , Células Madre Mesenquimatosas , Trasplante de Células Madre Mesenquimatosas/métodos , Aorta Abdominal/patologíaRESUMEN
Abdominal aortic aneurysm (AAA) is characterized by permanent luminal expansion and a high mortality rate due to aortic rupture. Despite the identification of abnormalities in the mevalonate pathway (MVA) in many diseases, including cardiovascular diseases, the potential impact of this pathway on AAA remains unclear. This study aims to investigate whether the expression of the MVA-related enzyme is altered during the progression of angiotensin II (Ang II) -induced AAA.Ang II 28D and Ang II 5D groups were continuously perfused with Ang II for 28 days and 5 days, respectively, and the Sham group was perfused with saline. The general and remodeling characteristics of AAA were determined by biochemical and histological analysis. Alteration of MVA-related enzyme expressions was revealed by western blot and single-cell RNA sequencing (scRNA-seq).The continuous Ang II infusion for 28 days showed significant aorta expansion and arterial remodeling. Although the arterial diameter slightly increased, the aneurysm formation was not found in Ang II induction for 5 days. MVA-related enzyme expression and activation of small GTP-binding proteins were significantly increased after Ang II-induced. As verified by scRNA-seq, the key enzyme gene expression was also higher in Ang II 28D. Similarly, it was detected that the expression levels of the above enzymes and the activity of small G proteins were elevated in the early stage of AAA as induced by Ang II infusion for 5 days.Continuous Ang II infusion-induced abdominal aortic expansion and arterial remodeling were accompanied by altered expression of key enzymes in the MVA.
Asunto(s)
Angiotensina II , Aneurisma de la Aorta Abdominal , Ácido Mevalónico , Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/inducido químicamente , Ácido Mevalónico/metabolismo , Animales , Masculino , Remodelación Vascular , Modelos Animales de Enfermedad , Aorta Abdominal/metabolismo , Aorta Abdominal/patologíaRESUMEN
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 (Pâ =â .019) than the no AL group, and the grade C AL group had higher portion of AAC (Pâ =â .016) than the no grade C AL group. In univariate logistic regression analysis, AAC was a significant potential factor for AL (Pâ =â .021, ORâ =â 1.739, 95% CIâ =â 1.088-2.779) and grade C AL (Pâ =â .019, ORâ =â 2.339, 95% CIâ =â 1.115-4.986). However, in multivariate logistic regression, AAC was not an independent predictive factor for AL (Pâ =â .157, ORâ =â 1.443, 95% CIâ =â 0.871-2.358) or grade C AL (Pâ =â .064, ORâ =â 2.055, 95% CIâ =â 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.
Asunto(s)
Fuga Anastomótica , Neoplasias del Recto , Calcificación Vascular , Humanos , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Masculino , Femenino , Fuga Anastomótica/etiología , Fuga Anastomótica/epidemiología , Persona de Mediana Edad , Anciano , Calcificación Vascular/diagnóstico por imagen , Estudios Retrospectivos , Aorta Abdominal/cirugía , Aorta Abdominal/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Enfermedades de la Aorta/cirugía , Factores de RiesgoRESUMEN
Pseudoaneurysms are false aneurysms that mostly occur at the site of arterial injury. Pseudoaneurysm is the most frequent complication after catheter-associated interventions and occurs because of an insufficient closure of the puncture site. However, there are several reported cases of patients with pseudoaneurysm without a prior history of vascular intervention. We described a case of ruptured giant abdominal aortic pseudoaneurysm in a patient with no prior history of vascular intervention, with an initial complaint of abdominal pain. The patient successfully received EVAR therapy using a kissing graft.
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Aneurisma Falso , Aneurisma de la Aorta Abdominal , Humanos , Aneurisma Falso/etiología , Aneurisma Falso/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Abdominal/complicaciones , Masculino , Rotura de la Aorta/cirugía , Rotura de la Aorta/etiología , Rotura de la Aorta/diagnóstico por imagen , Dolor Abdominal/etiología , Rotura Espontánea , Procedimientos Endovasculares , Aorta Abdominal/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Implantación de Prótesis Vascular , Persona de Mediana EdadRESUMEN
BACKGROUND: The long isoform of the Wnk1 (with-no-lysine [K] kinase 1) is a ubiquitous serine/threonine kinase, but its role in vascular smooth muscle cells (VSMCs) pathophysiology remains unknown. METHODS: AngII (angiotensin II) was infused in Apoe-/- to induce experimental aortic aneurysm. Mice carrying an Sm22-Cre allele were cross-bred with mice carrying a floxed Wnk1 allele to specifically investigate the functional role of Wnk1 in VSMCs. RESULTS: Single-cell RNA-sequencing of the aneurysmal abdominal aorta from AngII-infused Apoe-/- mice revealed that VSMCs that did not express Wnk1 showed lower expression of contractile phenotype markers and increased inflammatory activity. Interestingly, WNK1 gene expression in VSMCs was decreased in human abdominal aortic aneurysm. Wnk1-deficient VSMCs lost their contractile function and exhibited a proinflammatory phenotype, characterized by the production of matrix metalloproteases, as well as cytokines and chemokines, which contributed to local accumulation of inflammatory macrophages, Ly6Chi monocytes, and γδ T cells. Sm22Cre+Wnk1lox/lox mice spontaneously developed aortitis in the infrarenal abdominal aorta, which extended to the thoracic area over time without any negative effect on long-term survival. AngII infusion in Sm22Cre+Wnk1lox/lox mice aggravated the aortic disease, with the formation of lethal abdominal aortic aneurysms. Pharmacological blockade of γδ T-cell recruitment using neutralizing anti-CXCL9 (anti-CXC motif chemokine ligand 9) antibody treatment, or of monocyte/macrophage using Ki20227, a selective inhibitor of CSF1 receptor, attenuated aortitis. Wnk1 deletion in VSMCs led to aortic wall remodeling with destruction of elastin layers, increased collagen content, and enhanced local TGF-ß (transforming growth factor-beta) 1 expression. Finally, in vivo TGF-ß blockade using neutralizing anti-TGF-ß antibody promoted saccular aneurysm formation and aorta rupture in Sm22 Cre+ Wnk1lox/lox mice but not in control animals. CONCLUSION: Wnk1 is a key regulator of VSMC function. Wnk1 deletion promotes VSMC phenotype switch toward a pathogenic proinflammatory phenotype, orchestrating deleterious vascular remodeling and spontaneous severe aortitis in mice.
Asunto(s)
Angiotensina II , Aneurisma de la Aorta Abdominal , Aortitis , Músculo Liso Vascular , Miocitos del Músculo Liso , Proteína Quinasa Deficiente en Lisina WNK 1 , Animales , Aortitis/genética , Aortitis/metabolismo , Aortitis/patología , Ratones , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Aneurisma de la Aorta Abdominal/genética , Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/patología , Humanos , Proteína Quinasa Deficiente en Lisina WNK 1/genética , Proteína Quinasa Deficiente en Lisina WNK 1/metabolismo , Ratones Endogámicos C57BL , Masculino , Células Cultivadas , Ratones Noqueados para ApoE , Modelos Animales de Enfermedad , Inflamación/metabolismo , Inflamación/genética , Inflamación/patología , Aorta Abdominal/metabolismo , Aorta Abdominal/patologíaRESUMEN
BACKGROUND: Abdominal aorta-duodenal fistulas are rare abnormal communications between the abdominal aorta and duodenum. Secondary abdominal aorta-duodenal fistulas often result from endovascular surgery for aneurysms and can present as severe late complications. CASE PRESENTATION: A 50-year-old male patient underwent endovascular reconstruction for an infrarenal abdominal aortic pseudoaneurysm. Prior to the operation, he was diagnosed with Acquired Immune Deficiency Syndrome and Syphilis. Two years later, he was readmitted with lower extremity pain and fever. Blood cultures grew Enterococcus faecium, Salmonella, and Streptococcus anginosus. Sepsis was successfully treated with comprehensive anti-infective therapy. He was readmitted 6 months later, with blood cultures growing Enterococcus faecium and Escherichia coli. Although computed tomography did not show contrast agent leakage, we suspected an abdominal aorta-duodenal fistula. Esophagogastroduodenoscopy confirmed this suspicion. The patient underwent in situ abdominal aortic repair and received long-term antibiotic therapy. He remained symptom-free during a year and a half of follow-up. CONCLUSIONS: This case suggests that recurrent infections with non-typhoidal Salmonella and gut bacteria may be an initial clue to secondary abdominal aorta-duodenal fistula.
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Sepsis , Humanos , Masculino , Persona de Mediana Edad , Sepsis/microbiología , Sepsis/complicaciones , Aorta Abdominal/cirugía , Aorta Abdominal/microbiología , Enterococcus faecium/aislamiento & purificación , Antibacterianos/uso terapéutico , Streptococcus anginosus/aislamiento & purificación , Fístula Intestinal/microbiología , Fístula Intestinal/cirugía , Fístula Intestinal/complicaciones , Salmonella/aislamiento & purificación , Escherichia coli/aislamiento & purificación , Recurrencia , Enfermedades Duodenales/microbiología , Enfermedades Duodenales/cirugía , Enfermedades Duodenales/complicaciones , Infecciones por Salmonella/microbiología , Infecciones por Salmonella/complicaciones , Infecciones por Salmonella/diagnóstico , Infecciones por Salmonella/tratamiento farmacológicoRESUMEN
Recent studies have shown that microRNA-16-5p (miR-16-5p) plays a crucial role in the pathological mechanism of vascular calcification. Nevertheless, the expression profile of miR-16-5p in maintenance hemodialysis (MHD) patients who are predisposed to vascular calcification remains unknown. This study aims to investigate the potential associations between calcification risk and serum miR-16-5p expression among MHD patients. This cross-sectional study involved 132 MHD patients from the Dialysis Center of Beijing Friendship Hospital between 1 January 2019 and 31 December 2020. The degree of calcification in MHD patients was assessed using the Abdominal aortic calcification (AAC) score, and miR-16-5p expression was quantified using quantitative real-time polymerase chain reaction (qRT-PCR) with the 2-ΔΔCT method. Statistical analyses, including spearman correlation, linear regression and logistic regression analysis were used to explore the associations between laboratory parameters and AAC score. Calcifications were observed in 79(59.80%) patients. The linear regression showed a one-quartile decrease in miR-16-5p expression led to a significant increase in the AAC score by 5.336 (95% CI: 2.670-10.662, p = 0.000). Multivariate logistic regression analyses revealed that decreased miR-16-5p expression, reduced serum urea nitrogen, elevated white blood cell count, and longer dialysis vintage were significantly associated with an increased incidence of vascular calcification. The Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) of the miR-16-5p-based logistic regression model was 0.842 (95% CI: 0.771-0.913, p = 0.000). There was an independent association between miR-16-5p expression and calcification degree. Lower miR-16-5p expression levels seem to be a potential risk factor of vascular calcification in MHD patients.
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Aorta Abdominal , MicroARNs , Diálisis Renal , Calcificación Vascular , Humanos , MicroARNs/sangre , Masculino , Femenino , Diálisis Renal/efectos adversos , Calcificación Vascular/sangre , Calcificación Vascular/etiología , Persona de Mediana Edad , Aorta Abdominal/patología , Aorta Abdominal/diagnóstico por imagen , Estudios Transversales , Anciano , Fallo Renal Crónico/terapia , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Curva ROC , Factores de Riesgo , Modelos LogísticosRESUMEN
BACKGROUND: Abdominal aortic aneurysms expand over time and increase the risk of fatal ruptures. To predict expansion, the isolated assessment of 18F-fluorodeoxyglucose (FDG) and sodium fluoride (NaF) uptake or calcification volume in aneurysms has been investigated with variability in results. We systematically evaluated whether 18F-FDG and 18F-NaF uptake was predictive of abdominal aortic aneurysm expansion. METHODS: Seventy-four male Sprague-Dawley rat abdominal aortic aneurysm models were imaged using positron emission tomography-computed tomography with 18F-FDG and 18F-NaF at 1, 2, 4, 6, and 8 weeks after CaCl2 or saline stimulation. In the 1-week cohort (n=25), the correlation between 18F-FDG or 18F-NaF uptake and pathological markers was investigated. In the time course cohort (n=49), animals received either atorvastatin, losartan, aldactone, or risedronate to assess the effect of these drugs, and the relationship between aortic size and sequential 18F-FDG and 18F-NaF uptake or calcification volume was examined. RESULTS: In the 1-week cohort, the maximum standard unit value of 18F-FDG and 18F-NaF uptake correlated with CD68- (r=0.82; P=0.001) and von Kossa staining-positive areas (r=0.89; P<0.001), respectively. In the time course cohort, 18F-FDG and 18F-NaF uptake changed in a time-dependent manner and drugs attenuated this uptake. Specifically, 18F-FDG showed high uptake at weeks 1 and 2, whereas a high 18F-NaF uptake was noted throughout the study period. Atorvastatin and risedronate showed a decreased and increased aortic size, respectively. The final aortic area correlated well with 18F-FDG and 18F-NaF uptake and calcification volume, especially at 1 and 2 weeks (18F-NaF [1 week]: r=0.61, 18F-FDG [2 weeks]: r=0.51, calcification volume [1 week]: r=0.59; P<0.001). Multiple linear regression analysis showed that the combination of these factors predicted the final aortic size, with 18F-NaF uptake at 1 week being the strongest predictor. CONCLUSIONS: The uptake of 18F-NaF and 18F-FDG and the calcification volume at appropriate times correlated with the development of abdominal aortic aneurysms, with 18F-NaF uptake being the strongest predictor.
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Aorta Abdominal , Aneurisma de la Aorta Abdominal , Modelos Animales de Enfermedad , Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Ratas Sprague-Dawley , Fluoruro de Sodio , Calcificación Vascular , Animales , Masculino , Fluorodesoxiglucosa F18/farmacocinética , Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/inducido químicamente , Aorta Abdominal/diagnóstico por imagen , Aorta Abdominal/metabolismo , Aorta Abdominal/patología , Aorta Abdominal/efectos de los fármacos , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/metabolismo , Calcificación Vascular/patología , Valor Predictivo de las Pruebas , Factores de Tiempo , Radioisótopos de Flúor , Progresión de la Enfermedad , RatasRESUMEN
BACKGROUND: Inflammation is a key component in the development of abdominal aortic aneurysm (AAA), yet insights into the roles of immune cells and their interactions in this process are limited. METHODS: Using single-cell RNA transcriptomic analysis, we deconstructed the CD45+ cell population in elastase-induced murine AAA at the single-cell level. We isolated each group of immune cells from murine AAA tissue at different time points and divided them into several subtypes, listed the remarkable differentially expressed genes, explored the developmental trajectories of immune cells, and demonstrated the interactions among them. RESULTS: Our findings reveal significant differences in several immune cell subsets, including macrophages, dendritic cells, and T cells, within the AAA microenvironment compared with the normal aorta. Especially, conventional dendritic cell type 1 exclusively existed in the AAA tissue rather than the normal aortas. Via CellChat analysis, we identified several intercellular communication pathways like visfatin, which targets monocyte differentiation and neutrophil extracellular trap-mediated interaction between neutrophils and dendritic cells, which might contribute to AAA development. Some of these pathways were validated in human AAA. CONCLUSIONS: Despite the absence of external pathogenic stimuli, AAA tissues develop a complex inflammatory microenvironment involving numerous immune cells. In-depth studies of the inflammatory network shall provide new strategies for patients with AAA.
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Aorta Abdominal , Aneurisma de la Aorta Abdominal , Células Dendríticas , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Análisis de la Célula Individual , Aneurisma de la Aorta Abdominal/inmunología , Aneurisma de la Aorta Abdominal/genética , Aneurisma de la Aorta Abdominal/inducido químicamente , Aneurisma de la Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/metabolismo , Animales , Aorta Abdominal/patología , Aorta Abdominal/metabolismo , Aorta Abdominal/inmunología , Ratones , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Humanos , Macrófagos/metabolismo , Macrófagos/inmunología , Masculino , Transcriptoma , RNA-Seq , Linfocitos T/inmunología , Linfocitos T/metabolismo , Perfilación de la Expresión Génica/métodos , Elastasa Pancreática , Comunicación CelularRESUMEN
Introducción. Las complicaciones posteriores a la reparación endovascular de aneurisma (EVAR) pueden resolverse con técnicas endovasculares. Sin embargo, cuando está indicada, la explantación de una endoprótesis es un procedimiento complejo, que se asocia a lesiones vasculares o viscerales, con alta morbimortalidad, en pacientes con edad avanzada y múltiples comorbilidades, y por lo tanto, alto riesgo quirúrgico. No existen dispositivos producidos por la industria para explantar las endoprótesis aórticas, por lo que el objetivo de este trabajo fue desarrollar un dispositivo para la explantación de endoprótesis aórticas. Métodos. Se llevó a cabo un estudio experimental, en fase preclínica, para desarrollar un dispositivo para la explantación de endoprótesis aórticas, con pruebas en modelos 3D y en un modelo animal porcino cadavérico. Resultados. Es factible desarrollar un modelo experimental de un nuevo dispositivo para explantar endoprótesis aórticas, denominado explantador de Cabrera, y comprobar su funcionamiento en un modelo animal cadavérico. El uso del explantador de Cabrera limitó el daño de la pared aórtica por parte de la endoprótesis en un 100 % al momento de su explantación en un modelo experimental ex vivo. Conclusión. Usando una jeringa septo, el explantador de Cabrera es superior a la técnica estándar de explantación de una endoprótesis al limitar la lesión de la pared aórtica, al colapsar y liberar los ganchos de fijación suprarrenal de forma controlada y segura al interior de la luz aórtica y, posteriormente, extraerla de forma rápida y efectiva, conservando la mayor cantidad de aorta sana para la posterior reconstrucción aorto-ilíaca.
Introduction. Complications after endovascular aneurysm repair (EVAR) can be resolved with endovascular techniques; however, when indicated, stent explantation is a complex procedure, which is associated with vascular or visceral injuries, with high morbidity and mortality in patients, with advanced age and multiple comorbidities, and therefore high surgical risk. There are no devices produced by the industry to explant aortic endoprostheses, so the objective of this work was to develop a device for the explantation of aortic endoprostheses. Methods. An experimental study was carried out, in the preclinical phase, to develop a device for the explantation of aortic endoprostheses, with tests in 3D models and in a cadaveric porcine animal model. Results. It is feasible to develop an experimental model of a new device for explanting aortic endoprostheses, called Cabrera explanter, and verify its operation in a cadaveric animal model. The use of the Cabrera explanter limited damage to the aortic wall by the endoprosthesis by 100% at the time of explantation in an ex vivo experimental model. Conclusions. Using a septum syringe, the Cabrera explanter is superior to the standard stent explantation technique by limiting injury to the aortic wall, collapsing and releasing the adrenal fixation hooks in a controlled and safe manner into the aortic lumen, and subsequently, extract it quickly and effectively, preserving the greatest amount of healthy aorta for the subsequent aorto-iliac reconstruction.