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1.
Cardiol Rev ; 28(6): 308-311, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32941261

RESUMO

Cardiac involvement as a complication of severe acute respiratory syndrome coronavirus 2 infection in children is a relatively new entity. We present our initial experience managing children with coronavirus disease 2019-related acute myocardial injury. The 3 patients presented here represent a spectrum of the cardiac involvement noted in children with coronavirus disease 2019-related multisystem inflammatory syndrome, including myocarditis presenting as cardiogenic shock or heart failure with biventricular dysfunction, valvulitis, coronary artery changes, and pericardial effusion.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Insuficiência Cardíaca , Doenças das Valvas Cardíacas , Miocardite , Pandemias , Administração dos Cuidados ao Paciente/métodos , Derrame Pericárdico , Pneumonia Viral , Síndrome de Resposta Inflamatória Sistêmica , Adolescente , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Técnicas de Imagem Cardíaca/métodos , Criança , Pré-Escolar , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/virologia , Humanos , Miocardite/terapia , Miocardite/virologia , Derrame Pericárdico/terapia , Derrame Pericárdico/virologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Choque Cardiogênico/etiologia , Choque Cardiogênico/terapia , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Síndrome de Resposta Inflamatória Sistêmica/terapia , Resultado do Tratamento
2.
Angiology ; 71(9): 812-816, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32715720

RESUMO

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a heterogeneous entity with an inflammatory etiopathogenesis. This study investigated the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in patients with MINOCA. Coronary angiographies performed between June 2015 and August 2018 were analyzed retrospectively and included 72 patients with MINOCA and 248 controls with normal coronary angiograms. The predictors of mortality were determined by univariate Cox regression analysis. The mean age of the subjects was 46 ± 9 years, and 176 (55%) were female. Median follow-up was 21 (max: 42) months. Neutrophil-to-lymphocyte ratio was significantly higher in the MINOCA group than in the controls (P < .01). During long-term follow-up, the number of deaths was 6 in the MINOCA group and none in the control patients (P < .01). Univariate Cox regression analysis revealed that the NLR (hazard ratio: 1.24, 95% confidence interval: 1.09-1.41, P = .001) was a predictor of mortality in patients with MINOCA. Kaplan-Meier analysis also showed that patients with MINOCA had relatively higher mortality rate (long-rank test; P < .01). In conclusion, the NLR is significantly higher in patients with MINOCA compared with controls, and it is a predictor of long-term mortality.


Assuntos
Contagem de Linfócitos , Infarto do Miocárdio/sangue , Infarto do Miocárdio/mortalidade , Neutrófilos , Adulto , Angiografia Coronária , Vasos Coronários/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Prognóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Taxa de Sobrevida
3.
Med Hypotheses ; 143: 110117, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32721809

RESUMO

With rapid spread of severe acute respiratory syndrome- corona virus-2 (SARS-COV-2) globally, some new aspects of the disease have been reported. Recently, it has been reported the incidence of Kawasaki-like disease among children with COVID-19. Since, children had been known to be less severely affected by the virus in part due to the higher concentration of Angiotensin converting enzyme (ACE)-2 receptor, this presentation has emerged concerns regarding the infection of children with SARS-COV2. ACE2 has anti-inflammatory, anti-fibrotic and anti-proliferative characteristics through converting angiotensin (Ag)-II to Ang (1-7). ACE2 receptor is downregulated by the SARS-COV through the spike protein of SARS-CoV (SARS-S) via a process that is tightly coupled with Tumor necrosis factor (TNF)-α production. TNF-α plays a key role in aneurysmal formation of coronary arteries in Kawasaki disease (KD). Affected children by COVID-19 with genetically-susceptible to KD might have genetically under-expression of ACE2 receptor that might further decrease the expression of ACE2 due to the downregulation of the receptor by the virus in these patients. It appears that TNF- α might be the cause and the consequence of the ACE2 receptor downregulation which results in arterial walls aneurysm. Conclusion: Genetically under-expression of ACE2 receptor in children with genetically-susceptible to KD who are infected with SARS-CoV-2 possibly further downregulates the ACE2 expression by TNF-α and leads to surge of inflammation including TNF-α and progression to Kawasaki-like disease.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/complicações , Modelos Imunológicos , Síndrome de Linfonodos Mucocutâneos/etiologia , Pandemias , Pneumonia Viral/complicações , Ásia/epidemiologia , Criança , Vasos Coronários/imunologia , Vasos Coronários/patologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/genética , Síndrome da Liberação de Citocina/etiologia , Progressão da Doença , Endotélio Vascular/virologia , Predisposição Genética para Doença , Humanos , Inflamação , Ativação de Macrófagos , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Síndrome de Linfonodos Mucocutâneos/genética , Síndrome de Linfonodos Mucocutâneos/imunologia , Países Baixos/epidemiologia , Peptidil Dipeptidase A/biossíntese , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/genética , Receptores Virais/biossíntese , Receptores Virais/genética , Receptores Virais/fisiologia , Estações do Ano , Glicoproteína da Espícula de Coronavírus/fisiologia , Fator de Necrose Tumoral alfa/fisiologia , Estados Unidos/epidemiologia
4.
Arterioscler Thromb Vasc Biol ; 40(9): 1982-1989, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32673526

RESUMO

Atherosclerosis is a systemic disease that involves multiple vascular beds. The pathological characteristics and clinical presentation, however, vary among the different vascular territories. Acute coronary syndrome is a relatively common manifestation of coronary atherosclerotic disease, wherein the thrombosis occurs secondary to disruption (65%-75%) and erosion (25%-35%) of the fibrous caps of atheromatous plaques. The plaques associated with plaque rupture have large necrotic cores and thin and inflamed fibrous caps. However, the pathological manifestations of peripheral artery disease result from thrombosis regardless of the extent of atherosclerosis. Approximately 75% of peripheral arteries with significant stenosis demonstrate presence of thrombi, of which two-thirds have thrombi associated with insignificant atherosclerosis. The presence of obliterative thrombi in peripheral arteries of patients with critical limb ischemia in the absence of coronary artery-like lesions suggests a locally thrombogenic or remotely embolic basis of disease. Extensive calcification of the medial vascular layer is commonly observed. In this review, we have described and compared the pathological basis of coronary and peripheral artery disease in patients with acute coronary syndrome and critical limb ischemia. It is expected that pathogenetic characterization would allow for definition of strategic targets for superior management of peripheral artery disease.


Assuntos
Síndrome Coronariana Aguda/patologia , Artérias/patologia , Doença da Artéria Coronariana/patologia , Isquemia/patologia , Doença Arterial Periférica/patologia , Placa Aterosclerótica , Trombose/patologia , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/epidemiologia , Artérias/efeitos dos fármacos , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/epidemiologia , Vasos Coronários/patologia , Estado Terminal , Progressão da Doença , Fibrinolíticos/uso terapêutico , Fibrose , Humanos , Doença Arterial Periférica/tratamento farmacológico , Doença Arterial Periférica/epidemiologia , Prognóstico , Ruptura Espontânea , Trombose/tratamento farmacológico , Trombose/epidemiologia
5.
Arterioscler Thromb Vasc Biol ; 40(9): 2244-2264, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32640900

RESUMO

OBJECTIVE: Nanog is expressed in adult endothelial cells (ECs) at a low-level, however, its functional significance is not known. The goal of our study was to elucidate the role of Nanog in adult ECs using a genetically engineered mouse model system. Approach and Results: Biochemical analyses showed that Nanog is expressed in both adult human and mouse tissues. Primary ECs isolated from adult mice showed detectable levels of Nanog, Tert (telomerase reverse transcriptase), and eNos (endothelial nitric oxide synthase). Wnt3a (Wnt family member 3A) increased the expression of Nanog and hTERT (human telomerase reverse transcriptase) in ECs and increased telomerase activity in these cells. In a chromatin immunoprecipitation experiment, Nanog directly bound to the hTERT and eNOS promoter/enhancer DNA elements, thereby regulating their transcription. Administration of low-dose tamoxifen to ROSAmT/mG::Nanogfl/+::Cdh5CreERT2 mice induced deletion of a single Nanog allele, simultaneously labeling ECs with green fluorescent protein and resulting in decreased Tert and eNos levels. Histological and morphometric analyses of heart tissue sections prepared from these mice revealed cell death, microvascular rarefaction, and increased fibrosis in cardiac vessels. Accordingly, EC-specific Nanog-haploinsufficiency resulted in impaired EC homeostasis and angiogenesis. Conversely, re-expression of cDNA encoding the hTERT in Nanog-depleted ECs, in part, restored the effect of loss of Nanog. CONCLUSIONS: We showed that low-level Nanog expression is required for normal EC homeostasis and angiogenesis in adulthood.


Assuntos
Proliferação de Células , Senescência Celular , Vasos Coronários/metabolismo , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Proteína Homeobox Nanog/metabolismo , Animais , Apoptose , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Senescência Celular/efeitos dos fármacos , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/patologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Feminino , Fibrose , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Homeobox Nanog/deficiência , Proteína Homeobox Nanog/genética , Neovascularização Fisiológica , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Telomerase/genética , Telomerase/metabolismo , Ativação Transcricional , Via de Sinalização Wnt , Proteína Wnt3A/farmacologia
6.
Life Sci ; 258: 118136, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32726662

RESUMO

The endothelium is a critical regulator of vascular homeostasis, controlling vascular tone and permeability as well as interactions of leukocytes and platelets with blood vessel walls. Consequently, endothelial dysfunction featuring inflammation and reduced vasodilation are considered central to cardiovascular disease (CVD) pathogenesis and have become a therapeutic area of focus. Type II endothelial cell (EC) activation by stress-related stimuli such as tumor necrosis factor-α (TNF-α) initiates the nuclear factor-κB (NF-κB) signaling pathway, a master regulator of inflammatory responses. Because dysregulated NF-κB signaling has been tightly linked to several CVDs, EC-specific inhibition of NF-κB represents an attractive pharmacological strategy. As accumulating evidence highlights the clinical benefits of tea catechin for multiple diseases including CVDs, we sought to determine whether the tea catechin epigallocatechin gallate (EGCG) that displays antioxidative, anti-inflammatory, hypolipidemic, anti-thrombogenic, and anti-hypertensive properties offers protection against CVDs by suppressing the canonical NF-κB pathway. Our findings indicate that EGCG downregulates multiple components of the TNF-α-induced NF-κB signaling pathway and thereby reduces the consequent increase in inflammatory gene transcription and protein expression. Furthermore, EGCG blocked type II EC activation, evidenced by diminished EC leakage and monocyte adhesion in EGCG-treated cells. In summary, our study advances knowledge of EGCG's anti-inflammatory effects on the NF-κB pathway and hence its benefits on endothelial health, supporting its therapeutic potential for CVDs.


Assuntos
Catequina/análogos & derivados , Vasos Coronários/patologia , Células Endoteliais/patologia , Inflamação/tratamento farmacológico , Catequina/farmacologia , Catequina/uso terapêutico , Adesão Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Inflamação/genética , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Monócitos/efeitos dos fármacos , Monócitos/patologia , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
7.
Cardiovasc Diabetol ; 19(1): 109, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641042

RESUMO

BACKGROUND: Plaque rupture (PR) and plaque erosion (PE) are main causes of acute myocardial infarction with different demographic and histology characteristics and need different treatment strategy. PR and PE can be identified with optical coherence tomography (OCT) accurately, but convenient and effective noninvasive markers for them are rarely found. History of diabetes mellitus (DM) was reported to be a potential predictor of PR in ST-segment elevated myocardial infarction (STEMI) patients, but the predictive value of other glucose-related variables for it is still uncertain. Present study aimed to clear the relationship between some glucose-related variables and plaque morphology in patients with STEMI. METHODS: We consecutively enrolled 872 STEMI patients and divided them into PR group (n = 616) and PE group (n = 256) based on OCT diagnostic criteria. The relationship of glucose-related variables, including random plasma glucose on admission (ARPG), glycosylated hemoglobin (HbA1c), post-PCI fasting plasma glucose (PFPG), DM history, glucose variable tendency (GVT) and the acute-to-chronic glycemic ratio (A/C), to the PR risk of STEMI patients was analyzed. The correlation between the glucose-related variables and plaque morphology was analyzed meanwhile. RESULTS: Among the glucose-related variables, ARPG and GVT were confirmed to be independent predictors for PR after adjusting for other traditional risk factors in nondiabetic patients. The higher the ARPG level, the more PR risk the STEMI patients had. And high HbA1c and APPG were demonstrated to have a weak and positive correlation with lipid constituents and stenosis degree of culprit vessel. CONCLUSIONS: Compared to HbA1c, DM history, and some other glucose-related variables, ARPG and GVT were risk factors for PR in STEMI patients, especially those without DM. And high HbA1c and ARPG were positively correlated with the development of vulnerable plaque in culprit vessels. Trial registration Present study is a retrospective one and the population came from the EROSION study of our center previously. It was approved by the Ethics Committee of the Second Affiliated Hospital of Harbin Medical University (Approval reference number, KY2017-249), and all patients provided written informed consent prior to the inclusion in the study and the investigation conformed to the principles outlined in the Declaration of Helsinki.


Assuntos
Glicemia/metabolismo , Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Diabetes Mellitus/sangue , Placa Aterosclerótica , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Tomografia de Coerência Óptica , Biomarcadores/sangue , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/terapia , Vasos Coronários/patologia , Diabetes Mellitus/diagnóstico , Hemoglobina A Glicada/metabolismo , Humanos , Intervenção Coronária Percutânea , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Ruptura Espontânea , Infarto do Miocárdio com Supradesnível do Segmento ST/patologia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Fatores de Tempo
8.
Medicine (Baltimore) ; 99(28): e20850, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664079

RESUMO

RATIONALE: With the development and standardization of modern chronic total occlusions (CTOs) recanalization technique, percutaneous coronary intervention has become a promising treatment alternative to surgery after bypass graft failure. Treatment of a native coronary CTO lesion is preferable to treatment of a saphenous vein graft (SVG) CTO supplying the same territory; however, technical expertise is required. PATIENT CONCERNS: This is a 69-year-old male with prior history of coronary artery bypass grafting presented with severe dyspnea at mild exertion (NYHA III) of 2 months duration. DIAGNOSIS: The patient was diagnosed as heart failure caused by ischemia after SVG failure (SVG to right coronary artery) according to electrocardiogram, plasma N-terminal pro-B-type natriuretic peptide levels, and coronary angiogram. INTERVENTIONS: We recanalized native right coronary artery CTO by retrograde approach using septal collaterals by surfing technique after recanalization of totally occluded left coronary artery. OUTCOMES: Dyspnea was relieved at discharge. At 6-month follow-up, the patient had no recurrence of dyspnea. LESSONS: In case of SVG failure, percutaneous coronary intervention of native vessel should be considered as a treatment option. Retrograde approach through native vessel is safe but has requirements for operators' volume, skill, and experience.


Assuntos
Vasos Coronários/cirurgia , Dispneia/etiologia , Insuficiência Cardíaca/diagnóstico , Veia Safena/transplante , Assistência ao Convalescente , Idoso , Angiografia Coronária/métodos , Ponte de Artéria Coronária/efeitos adversos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Eletrocardiografia/métodos , Oclusão de Enxerto Vascular/complicações , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Intervenção Coronária Percutânea/métodos , Resultado do Tratamento
9.
Asian Cardiovasc Thorac Ann ; 28(6): 312-315, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32551839

RESUMO

BACKGROUND: Coronary artery ectasia is a relatively common entity characterized by inappropriate dilatation of the coronary vasculature. In some cases of acute coronary syndrome without obstructive coronary lesions, coronary ectasia is the sole cause. The exact mechanism of its development is unknown but evidence suggests a combination of genetic predisposition, common risk factors for coronary artery disease, and abnormal vessel wall metabolism. As there are few data regarding the pattern of coronary risk factors in patients with coronary ectasia, the objective of the study was to determine the frequency and distribution of coronary risk factors in patients with acute coronary syndrome solely due to coronary ectasia. METHODS: The study included 155 patients over a period of 6 months, with coronary angiographic evidence of coronary ectasia as the sole cause of acute coronary syndrome. There were 79 (51%) men and 76 (49%) women with a mean age 51.92 ± 7.83 years; 73 (47.10%) were aged 20-50 years and 82 (52.90%) were 51-80 years of age. The frequencies of coronary risk factors were stratified according to sex and the two age groups. RESULTS: Seventy-one patients (45.80%) had diabetes mellitus, 83 (53.54%) had hypertension, 55 (35.48%) were smokers, 46 (29.68%) had dyslipidemia, and 47 (30.3%) were obese. CONCLUSION: Hypertension is the leading coronary risk factors in patients with acute coronary syndrome solely due to coronary ectasia, followed by diabetes mellitus and smoking.


Assuntos
Síndrome Coronariana Aguda/epidemiologia , Aneurisma Coronário/epidemiologia , Síndrome Coronariana Aguda/diagnóstico por imagem , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/patologia , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Estudos Transversais , Diabetes Mellitus/epidemiologia , Dilatação Patológica , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Medição de Risco , Fatores de Risco , Distribuição por Sexo , Fumar/efeitos adversos , Fumar/epidemiologia , Adulto Jovem
10.
Transl Res ; 224: 40-54, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32522668

RESUMO

The modulation of voltage-gated K+ (Kv) channels, involved in cell proliferation, arises as a potential therapeutic approach for the prevention of intimal hyperplasia present in in-stent restenosis (ISR) and allograft vasculopathy (AV). We studied the effect of PAP-1, a selective blocker of Kv1.3 channels, on development of intimal hyperplasia in vitro and in vivo in 2 porcine models of vascular injury. In vitro phenotypic modulation of VSMCs was associated to an increased functional expression of Kv1.3 channels, and only selective Kv1.3 channel blockers were able to inhibit porcine VSMC proliferation. The therapeutic potential of PAP-1 was then evaluated in vivo in swine models of ISR and AV. At 15-days follow-up, morphometric analysis demonstrated a substantial reduction of luminal stenosis in the allografts treated with PAP-1 (autograft 2.72 ± 1.79 vs allograft 10.32 ± 1.92 vs allograft + polymer 13.54 ± 8.59 vs allograft + polymer + PAP-1 3.06 ± 1.08 % of luminal stenosis; P = 0.006) in the swine model of femoral artery transplant. In the pig model of coronary ISR, using a prototype of PAP-1-eluting stent, no differences were observed regarding % of stenosis compared to control stents (31 ± 13 % vs 37 ± 18%, respectively; P = 0.372) at 28-days follow-up. PAP-1 treatment was safe and did not impair vascular healing in terms of delayed endothelialization, inflammation or thrombosis. However, an incomplete release of PAP-1 from stents was documented. We conclude that the use of selective Kv1.3 blockers represents a promising therapeutic approach for the prevention of intimal hyperplasia in AV, although further studies to improve their delivery method are needed to elucidate its potential in ISR.


Assuntos
Canal de Potássio Kv1.3/antagonistas & inibidores , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Bloqueadores dos Canais de Potássio/farmacologia , Túnica Íntima/patologia , Aloenxertos/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Reestenose Coronária/patologia , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/lesões , Vasos Coronários/patologia , Modelos Animais de Doenças , Feminino , Artéria Femoral/efeitos dos fármacos , Artéria Femoral/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperplasia , Canal de Potássio Kv1.3/genética , Canal de Potássio Kv1.3/metabolismo , Canal de Potássio Kv1.5/genética , Canal de Potássio Kv1.5/metabolismo , Modelos Biológicos , Miócitos de Músculo Liso/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Stents , Suínos , Túnica Íntima/efeitos dos fármacos
11.
PLoS One ; 15(5): e0232735, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32379805

RESUMO

BACKGROUND: Atherosclerosis is the primary cause of coronary artery disease (CAD). Several observational studies have examined the association of traditional CAD risk factors with the progression of coronary artery calcification (CAC). In our study we investigated the effect of 11 different genetic risk scores associated with CAD and CAD risk factors on the progression of CAC. METHODS AND RESULTS: We included 3097 participants from the Heinz Nixdorf Recall study who had available CAC measurements at baseline (CACb) and at the 5-year follow-up (CAC5y). A weighted genetic risk score for CAD and each of the CAD-associated risk factors was constructed. Multiple regression analyses were applied to i) the difference between the observed log(CAC5y+1) (log(obs)) and expected log(CAC5y+1) (log(exp)) at the 5-year follow-up following the individual's log(CACb+1) percentile for the time between scans (log(obs)-log(exp)) and ii) the 5-year CAC progression, defined as 5*(log(CAC5y+1)-log(CACb+1))/time between the scans, adjusted for age, sex, and log(CACb+1) as well as for risk factors. The median percent deviation from the expected (CAC5y+1) and the 5-year progression of (CAC+1) in our study were 0 (first quartile: Q1; third quartile: Q3: -0.32; 0.48) and 45.4% (0%; 171.0%) respectively. In the age-, sex- and log(CACb+1)-adjusted model, the per-standard deviation (SD) increase in CAD genetic risk score was associated with the percent deviation from the expected (CAC5y+1) (9.7% (95% confidence interval: 5.2%; 14.5%), p = 1.6x10-5) and the 5-year progression of CAC (7.1% (3.0%; 11.4%), p = 0.0005). The CAD genetic risk score explains an additional 0.6% of the observed phenotypic variance for "log(obs)-log(exp)" and 0.4% for 5-year progression of CAC. Additionally, the per-SD increase in the CAC genetic risk score was associated with the percent deviation from the expected (CAC5y+1) (6.2% (1.9%; 10.8%, p = 0.005)) explaining an additional 0.2% of the observed phenotypic variance. However, the per-SD increase in the CAC genetic risk score was not associated with the 5-year progression of CAC (4.4% (0.4%; 8.5%), p = 0.03) after multiple testing. Adjusting for risk factors did not change the results. None of the other genetic risk scores showed an association with the percent deviation from the expected (CAC5y+1) or with the 5-year progression of CAC. CONCLUSIONS: The association of the CAC genetic risk score and the CAD genetic risk score provides evidence that genetic determinants for CAC and CAD influence the progression of CAC.


Assuntos
Doença da Artéria Coronariana/genética , Vasos Coronários/patologia , Calcificação Vascular/genética , Idoso , Doença da Artéria Coronariana/patologia , Vasos Coronários/metabolismo , Progressão da Doença , Feminino , Seguimentos , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Calcificação Vascular/patologia
12.
PLoS One ; 15(5): e0232483, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32392256

RESUMO

BACKGROUND: Percutaneous coronary intervention represents the most important treatment modality of coronary artery stenosis. In-stent restenosis (ISR) is still a limitation for the long-term outcome despite the introduction of drug eluting stents. It has been shown that adipokines directly influence vessel wall homeostasis by influencing the function of endothelial cells and arterial smooth muscle cells. Visceral adipose tissue-derived serpin vaspin was recently identified as a member of serine protease inhibitor family and serveral studies could demonstrate a relation to metabolic diseases. The aim of this study was to investigate a role of vaspin in the development of in-stent restenosis in vivo and on migration of smooth muscle cells and endothelial cells in vitro. METHODS: We studied 85 patients with stable coronary artery disease who underwent elective and successful PCI with implatation of drug eluting stents. Blood samples were taken directly before PCI. Vaspin plasma levels were measured by specific ELISA. ISR was evaluated eight months later by coronary angiography. Human coronary artery smooth muscle cells (HCASMC) and human umbilical vein endothelial cells (HUVEC) migration was analyzed by an in-vitro migration assay with different concentrations (0.004ng/mL up to 40ng/mL) of vaspin as well as by an scratch assay. For proliferation an impedance measurement with specialiced E-Plates was performed. RESULTS: During the follow up period, 14 patients developed ISR. Patients with ISR had significantly lower vaspin plasma levels compared to patients without ISR (0.213 ng/ml vs 0.382 ng/ml; p = 0.001). In patients with plasma vaspin levels above 1.35 ng/ml we could not observe any restenosis. There was also a significant correlation of plasma vaspin levels and late lumen loss in the stented coronary segments. Further we could demonstrate that vaspin nearly abolishes serum induced migration of HCASMC (100% vs. 9%; p<0.001) in a biphasic manner but not migration of HUVEC. Proliferation of HCASMC and HUVEC was not modulated by vaspin treatment. CONCLUSION: We were able to show that the adipokine vaspin selectively inhibits human coronary SMC migration in vitro and has no effect on HUVEC migration. Vaspin had no effect on proliferation of HUVEC which is an important process of the healing of the stented vessel. In addition, the occurrence of ISR after PCI with implantation of drug eluting stents was significantly associated with low vaspin plasma levels before intervention. Determination of vaspin plasma levels before PCI might be helpful in the identification of patients with high risk for development of ISR after stent implantation. In addition, the selective effects of vaspin on smooth muscle cell migration could potentially be used to reduce ISR without inhibition of re-endothelialization of the stented segment.


Assuntos
Adipocinas/fisiologia , Reestenose Coronária/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Serpinas/fisiologia , Adipocinas/sangue , Adipocinas/farmacologia , Idoso , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Células Cultivadas , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/cirurgia , Reestenose Coronária/patologia , Reestenose Coronária/fisiopatologia , Vasos Coronários/patologia , Vasos Coronários/fisiopatologia , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Miócitos de Músculo Liso/fisiologia , Serpinas/sangue , Serpinas/farmacologia
13.
Gene ; 753: 144806, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32461018

RESUMO

BACKGROUND: The aim of the present study was to detect potential gender-specific associations between some common CD36 single nucleotide polymorphisms (SNPs) and the lipid profile, as well as the susceptibility to premature multi-vessel coronary artery heart disease (CHD) in the Han population of Northern China. METHODS: A systematic three-step study process was employed to detect associations between CD36 gene variants and blood lipid profiles, as well as premature multi-vessel CHD in a gender-specific manner. RESULTS: The current study documented the following novel findings: (I) the full population-based association study in 329 Northern Han Chinese showed that four common CD36 polymorphisms were significantly related to extreme lipid profiles, with statistically significant effects based on gender interactions (rs1049673: P = 0.001; rs7755: P = 0.008; rs3211956: P = 0.034; and rs3173798: P = 0.004); (ii) these statistically significant effects could be decomposed into statistically significant atherogenic effects in males, but non-significant non-atherogenic effects in females; (iii) the results of logistic regression analysis indicated that current smoking status, low density lipoprotein cholesterol (LDL-C) levels, and type-2 diabetes were independent risk factors for premature multi-vessel CHD phenotype (P < 0.0001). CONCLUSIONS: Four common CD36 polymorphisms (rs1049673, rs7755, rs3211956, and rs3173798) were identified to be significantly associated with extreme lipid profiles and had statistically opposite gender-specific clinical lipid profile effects. Thus, the 3'-untranslated regions (3'-UTR) CD36 SNPs could be a novel target for metabolic abnormalities in males of the Han nationality from Northern China.


Assuntos
Antígenos CD36/genética , Doença da Artéria Coronariana/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Aterosclerose/sangue , Aterosclerose/genética , Aterosclerose/patologia , Estudos de Casos e Controles , China/epidemiologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/patologia , Vasos Coronários/patologia , Grupos Étnicos/genética , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Lipídeos/sangue , Lipídeos/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Caracteres Sexuais
14.
Am J Physiol Cell Physiol ; 319(1): C166-C182, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32432929

RESUMO

This review aims to highlight the normal physiological remodeling that occurs in healthy aging hearts, including changes that occur in contractility, conduction, valve function, large and small coronary vessels, and the extracellular matrix. These "normal" age-related changes serve as the foundation that supports decreased plasticity and limited ability for tissue remodeling during pathophysiological states such as myocardial ischemia and heart failure. This review will identify populations at greater risk for poor tissue remodeling in advanced age along with present and future therapeutic strategies that may ameliorate dysfunctional tissue remodeling in aging hearts.


Assuntos
Envelhecimento Saudável/patologia , Cardiopatias/patologia , Miocárdio/patologia , Remodelação Ventricular/fisiologia , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Envelhecimento Saudável/metabolismo , Cardiopatias/metabolismo , Humanos , Miocárdio/metabolismo
16.
Arterioscler Thromb Vasc Biol ; 40(6): 1587-1597, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32295419

RESUMO

OBJECTIVE: Healed plaques, signs of previous plaque destabilization, are frequently found in the coronary arteries. Healed plaques can now be diagnosed in living patients. We investigated the prevalence, angiographic, and optical coherence tomography features of healed plaques in patients with stable angina pectoris. Approach and Results: Patients with stable angina pectoris who had undergone optical coherence tomography imaging were included. Healed plaques were defined as plaques with one or more signal-rich layers of different optical density. Patients were divided into 2 groups based on layered or nonlayered phenotype at the culprit lesion. Among 163 patients, 87 (53.4%) had layered culprit plaque. Patients with layered culprit plaque had more multivessel disease (62.1% versus 44.7%, P=0.027) and more angiographically complex culprit lesions (64.4% versus 35.5%, P<0.001). Layered culprit plaques had higher prevalence of lipid plaque (83.9% versus 64.5%, P=0.004), macrophage infiltration (58.6% versus 35.5%, P=0.003), calcifications (78.2% versus 63.2%, P=0.035), and thrombus (28.7% versus 14.5%, P=0.029). Lipid index (P=0.001) and percent area stenosis (P=0.015) were greater in the layered group. The number of nonculprit plaques, evaluated using coronary angiograms, tended to be greater in patients with layered culprit plaque (4.2±2.5 versus 3.5±2.1, P=0.053). Nonculprit plaques in patients with layered culprit lesion had higher prevalence of layered pattern (P=0.002) and lipid phenotype (P=0.005). Lipid index (P=0.013) and percent area stenosis (P=0.002) were also greater in this group. CONCLUSIONS: In patients with stable angina pectoris, healed culprit plaques are common and have more features of vulnerability and advanced atherosclerosis both at culprit and nonculprit lesions.


Assuntos
Angina Estável/patologia , Placa Aterosclerótica/patologia , Idoso , Doença da Artéria Coronariana/patologia , Estenose Coronária/patologia , Trombose Coronária/patologia , Vasos Coronários/patologia , Feminino , Humanos , Lipídeos/análise , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Tomografia de Coerência Óptica , Calcificação Vascular/patologia
17.
J Med Life ; 13(1): 98-101, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32341709

RESUMO

Here we present a case of a 70-year-old man with acute myocardial infarction caused by left anterior descending artery occlusion presenting as ST elevation in the inferior leads that suggested an occlusion of the right coronary artery. In contrast, coronary angiography results indicated a complete occlusion of the proximal left anterior descending coronary artery. We reported our observation in electrocardiographic data and coronary angiography and its changes after a percutaneous coronary intervention, and then we discuss its pathophysiologic mechanism.


Assuntos
Arteriopatias Oclusivas/complicações , Vasos Coronários/patologia , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Potenciais de Ação , Idoso , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/fisiopatologia , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/fisiopatologia , Eletrocardiografia , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia
18.
J Vis Exp ; (156)2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32150171

RESUMO

Minimally invasive methods for creating models of focal coronary narrowing in large animals are challenging. Rapid prototyping using three-dimensionally (3D) printed coronary implants can be employed to percutaneously create a focal coronary stenosis. However, reliable delivery of the implants can be difficult without the use of ancillary equipment. We describe the use of a mother-and-child coronary guide catheter for stabilization of the implant and for effective delivery of the 3D printed implant to any desired location along the length of the coronary vessel. The focal coronary narrowing was confirmed under coronary cineangiography and the functional significance of the coronary stenosis was assessed using gadolinium-enhanced first-pass cardiac perfusion MRI. We showed that reliable delivery of 3D printed coronary implants in swine models (n = 11) of ischemic heart disease can be achieved through repurposing mother-and-child coronary guide catheters. Our technique simplifies the percutaneous delivery of coronary implants to create closed-chest swine models of focal coronary artery stenosis and can be performed expeditiously, with a low procedural failure rate.


Assuntos
Cateteres Cardíacos , Estenose Coronária/fisiopatologia , Vasos Coronários/patologia , Modelos Animais de Doenças , Isquemia Miocárdica/patologia , Impressão Tridimensional/instrumentação , Próteses e Implantes , Animais , Angiografia Coronária , Gadolínio , Imagem por Ressonância Magnética , Masculino , Suínos
19.
EuroIntervention ; 16(3): 201-209, 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32122821

RESUMO

AIMS: We aimed to investigate the association between the use and findings of IVUS with clinical outcomes in the PCI arm of a randomised trial of LMS PCI. METHODS AND RESULTS: The NOBLE trial randomised patients with LMS disease to treatment by PCI or CABG. Of 603 patients treated by PCI, 435 (72%) underwent post-PCI IVUS assessment, 224 of which were analysed in a core laboratory. At five years, the composite of MACCE was 18.9% if post-PCI IVUS was performed versus 25.0% if it was not performed (p=0.45, after adjustment). Overall repeat revascularisation was not reduced (10.6% vs 16.5%, p=0.11); however, LMS TLR was (5.1% vs 11.6%, p=0.01) if IVUS was used. For comparison of stent expansion, LMS MSA was split into tertiles. We found no significant difference in MACCE, death, myocardial infarction or stent thrombosis between tertiles. There was a significant difference between the lower and upper tertiles for repeat revascularisation (17.6% vs 5.2%, p=0.02) and LMS TLR (12.2% vs 0%, p=0.002). CONCLUSIONS: Post-PCI IVUS assessment and adequate stent expansion are not associated with reduced MACCE; however, there is an association with reduced LMS TLR. The use of intracoronary imaging to prevent stent underexpansion in LMS PCI is likely to improve outcomes.


Assuntos
Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea/métodos , Ultrassonografia de Intervenção/métodos , Vasos Coronários/patologia , Stents Farmacológicos/normas , Humanos , Resultado do Tratamento
20.
Nat Commun ; 11(1): 1315, 2020 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-32161256

RESUMO

Myocardial ischemia is one of the leading health problems worldwide. Therapy consists of the restitution of coronary perfusion which is followed by myocardial inflammation. Platelet-neutrophil interaction is a crucial process during inflammation, yet its consequences are not fully understood. Here, we show that platelet-neutrophil complexes (PNCs) are increased in patients with acute myocardial infarction and that this is associated with increased levels of neuronal guidance protein semaphorin 7A (SEMA7A). To investigate this further, we injected WT animals with Sema7a and found increased infarct size with increased numbers of PNCs. Experiments in genetically modified animals identify Sema7a on red blood cells to be crucial for this condition. Further studies revealed that Sema7a interacts with the platelet receptor glycoprotein Ib (GPIb). Treatment with anti-Sema7a antibody protected from myocardial tissue injury. In summary, we show that Sema7a binds to platelet GPIb and enhances platelet thrombo-inflammatory activity, aggravating post-ischemic myocardial tissue injury.


Assuntos
Antígenos CD/metabolismo , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Semaforinas/metabolismo , Trombose/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antígenos CD/genética , Antígenos CD/imunologia , Plaquetas/imunologia , Plaquetas/metabolismo , Vasos Coronários/patologia , Modelos Animais de Doenças , Eritrócitos/imunologia , Eritrócitos/metabolismo , Feminino , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/imunologia , Proteínas Ligadas por GPI/metabolismo , Humanos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/imunologia , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/imunologia , Miocárdio/patologia , Estudos Prospectivos , Semaforinas/genética , Semaforinas/imunologia , Trombose/imunologia , Adulto Jovem
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