scholarly journals Deficiency of MMP1a (Matrix Metalloprotease 1a) Collagenase Suppresses Development of Atherosclerosis in Mice

2021 ◽  
Author(s):  
Elizabeth K. Fletcher ◽  
Yanling Wang ◽  
Laura K. Flynn ◽  
Susan E. Turner ◽  
Jeffrey J. Rade ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Acute Coronary Syndrome ◽  
Coronary Artery ◽  
Atherosclerotic Plaque ◽  
Disease Burden ◽  
Oxidized Ldl ◽  
Plaque Burden ◽  
Matrix Metalloprotease ◽  
Coronary Syndrome ◽  
Artery Disease

Objective: Destruction of arterial collagen allows monocyte and macrophage infiltration leading to atherosclerotic plaque formation, but it is not clear what role the MMP1 (matrix metalloprotease 1) collagenase plays in this process in vivo. To define the specific contribution of MMP1 to atherosclerotic plaque burden and pathogenesis, we generated ApoE −/− mice deficient in the human MMP1 ortholog, MMP1a. Approach and Results: After 12 to 16 weeks of Western diet, genetic loss of MMP1a resulted in a significant 50% reduction in total aortic plaque burden compared with control ApoE −/− mice. MMP1a deficiency led to significant reductions in plaque monocytes/macrophages, SMCs, and necrosis, with increases in collagen content. Collagen invasion of oxidized-LDL (low-density lipoprotein) activated peripheral blood mononuclear cells from MMP1a-deficient mice was markedly attenuated and was similar to suppressive effects with pharmacological inhibitors of MMP1 and its receptor, PAR1 (protease-activated receptor 1). Patients with coronary artery disease and acute coronary syndrome undergoing cardiac catheterization in the TRIP-PCI trial were evaluated for circulating levels of all 3 major secreted collagenases, MMP1, MMP8, and MMP13 and total number of coronary lesions with ≥50% stenosis (coronary artery disease burden). MMP1 was significantly ( P <0.001) higher by 19-fold and 5.7-fold relative to MMP13 and MMP8, respectively. MMP1 correlated with stenotic coronary artery disease burden, TNFα (tumor necrosis factor alpha) levels, and was co-expressed with PAR1 on monocytes. Treatment of patients with the PAR1 inhibitor, PZ-128, prevented a drop in monocytes following coronary catheterization, an acute protective effect that was reproduced in mice undergoing cardiac ischemia reperfusion. Conclusions: These data provide evidence for an important role for the MMP1a collagenase in atherosclerotic lesion development and leukocyte behavior and validate MMP1 as a compelling target in patients with coronary artery disease/acute coronary syndrome. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02561000.

scholarly journals Glomerular Filtration Rate and Coronary Artery Disease Burden in Patients with Acute Coronary Syndrome

2007 ◽  
Vol 30 (9) ◽  
pp. 464-468 ◽  
Author(s):  
José Pedro L. Nunes ◽  
Maria do Sameiro Faria ◽  
J. M. Mota Garcia ◽  
Francisco Rocha Gonçalves
Keyword(s):  
Coronary Artery Disease ◽  
Acute Coronary Syndrome ◽  
Glomerular Filtration Rate ◽  
Coronary Artery ◽  
Glomerular Filtration ◽  
Disease Burden ◽  
Filtration Rate ◽  
Coronary Syndrome ◽  
Artery Disease

Admission Heart Rate Is Associated With Coronary Artery Disease Severity and Complexity in Patients With Acute Coronary Syndrome

Angiology ◽  
2019 ◽  
Vol 70 (8) ◽  
pp. 774-781 ◽  
Author(s):  
Xiaoteng Ma ◽  
Zhijian Wang ◽  
Jianlong Wang ◽  
Fang Liu ◽  
Dai Zhang ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Heart Rate ◽  
Acute Coronary Syndrome ◽  
Coronary Artery ◽  
Disease Severity ◽  
Plaque Burden ◽  
Syntax Score ◽  
Coronary Syndrome ◽  
Coronary Artery Disease Severity ◽  
Artery Disease

We evaluated the relationship between admission heart rate (HR) and coronary artery disease severity and complexity in patients with acute coronary syndrome (ACS). A total of 884 patients (mean age 59 [11] years, 24.7% female) who underwent coronary angiography for ACS and were treated with primary or selective percutaneous coronary intervention were included in this cross-sectional study. The measurement of admission HR was based on the first available resting electrocardiogram after admission. The SYNTAX score (SS) was calculated. Patients with an SS ≤ 22 (n = 538) were classified as the low SS group and those with an SS > 22 (n = 346) were classified as the intermediate-to-high SS group. Admission HR was greater in the intermediate-to-high SS group compared with the low SS group (75 [10] bpm vs 67 [8] bpm, P < .001). Admission HR was positively and significantly correlated with the SS ( r = 0.475, P < .001). After multivariate analysis, admission HR (per 1 standard deviation, ie, 10 bpm) remained an independent predictor of intermediate-to-high SS (odds ratio: 3.135, 95% confidence interval: 2.538-3.873, P < .001). Admission HR is independently and positively associated with the SS. Thus, elevated admission HR may be useful to identify patients with ACS with a high coronary atherosclerotic plaque burden.

Abstract 4223: Low Adiponectin Levels Are an Independent Predictor of Mixed and Non-Calcified Coronary Atherosclerotic Plaques

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Uli C Broedl ◽  
Corinna Lebherz ◽  
Michael Lehrke ◽  
Renee Stark ◽  
Helmholtz Zentrum ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Acute Coronary Syndrome ◽  
Coronary Artery ◽  
Coronary Plaque ◽  
Plaque Burden ◽  
Atherosclerotic Plaques ◽  
Atypical Chest Pain ◽  
Coronary Syndrome ◽  
Coronary Atherosclerotic Plaque ◽  
Artery Disease

We sought to examine the relationship of adiponectin with coronary atherosclerotic plaque morphology in patients with stable typical or atypical chest pain. There is increasing recognition that lesion composition rather than size determines the acute complications of atherosclerotic disease. Low serum adiponectin levels are associated with coronary artery disease and future incidence of acute coronary syndrome. The impact of adiponectin on lesion composition still remains to be determined. Serum adiponectin levels were determined in 303 patients with stable typical or atypical chest pain, who underwent dual-source multi-slice CT-angiography to exclude coronary artery stenosis. Atherosclerotic plaques were classified as calcified, mixed or non-calcified plaques. In bivariate analysis adiponectin levels were inversely correlated with total coronary plaque burden (r=−0.22, p<0.0001), mixed (r=−0.20, p=0.0007) and non-calcified plaques (r=−0.18, p=0.003). No correlation was seen with calcified plaques (r=−0.05, p=0.39). In a fully adjusted multivariate model containing age, sex, body mass index, hypertension, diabetes mellitus, smoking, family history of coronary artery disease, LDL-cholesterol, HDL-cholesterol, triglycerides, hsCRP levels, medication and pericardial adipose tissue volume, adiponectin levels remained predictive of total plaque burden (estimate: −0.035, 95% CI: −0.051 to −0.019, p<0.0001), mixed (estimate: −0.083, 95% CI: −0.127 to −0.039, p=0.0002) and non-calcified plaques (estimate: −0.076, 95% CI: −0.114 to −0.038, p=0.0001). Since the majority of coronary plaques were calcified plaques, adiponectin levels account for only 3% of the variability in total plaque number. In contrast, adiponectin accounts for approximately 20% of the variability in mixed and non-calcified plaque burden. Adiponectin levels predict mixed and non-calcified coronary atherosclerotic plaque burden. Low adiponectin levels may contribute to coronary plaque vulnerability and may thus play a role in the pathophysiology of acute coronary syndrome.

Study on Vitamin D deficiency in patients of diabetes mellitus presenting with Acute Coronary syndrome in a tertiary care hospital in South India

2020 ◽  
Vol 11 (5) ◽  
pp. 49-53
Author(s):  
Archana Bhat ◽  
Arunachalam Ramachandran ◽  
Pradeep Periera ◽  
Akshatha Rao Aroor
Keyword(s):  
Diabetes Mellitus ◽  
Coronary Artery Disease ◽  
Vitamin D ◽  
Acute Coronary Syndrome ◽  
Coronary Artery ◽  
Vitamin D Deficiency ◽  
Coronary Syndrome ◽  
Vitamin D Levels ◽  
Luminal Stenosis ◽  
Artery Disease

Background: Vitamin D, a fat-soluble vitamin has its receptor present in myriad of tissues and it modulates multiple cellular processes. Vitamin D deficiency is reported to be associated with coronary artery disease. Cardiovascular disease is the leading cause of mortality worldwide. Aims and Objective: The primary outcome was to investigate if there is a correlation of 25-OH levels with the percentage of luminal stenosis, as measured with coronary angiogram. The secondary outcome was to determine the differences in angiographically proven luminal stenosis across categories of 25-OH vitamin D levels. Materials and Methods: Thirty patients with acute coronary syndrome with diabetes mellitus were included in this cross-sectional descriptive study. All patients were tested for fasting vitamin D levels, fasting blood sugar, HbA1C and serum creatinine. Detailed history of the patients was recorded. Data was analyzed by the statistical software SPSS version 19 and p value <0.05 was considered significant. Statistical tests like Chi- square, independent t test and log regression was used. Results: In this study 30 patients undergoing coronary angiography for acute coronary syndrome, Vitamin D levels showed severe deficiency in 6.7% (2) cases while mild deficiency was seen in 50% of the cases. Patients with single vessel disease on the coronary angiogram had lower mean HbA1C (9.18) levels in our study. Patients with triple vessel disease had poorly controlled mean HbA1C levels (10.42). Conclusion: In this study we did not find any significant difference between the serum Vitamin D deficiency levels with patients with angiographic severity of the coronary artery disease. Patients with poorly controlled diabetes mellitus had more severe angiographic proven coronary artery disease.

scholarly journals Severe Coronary Artery Disease in a Person Living with HIV

Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 595
Author(s):  
Mircea Bajdechi ◽  
Cosmin Mihai ◽  
Alexandru Scafa-Udriste ◽  
Ali Cherry ◽  
Diana Zamfir ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Acute Coronary Syndrome ◽  
Coronary Artery ◽  
Severe Coronary Artery Disease ◽  
Atypical Symptoms ◽  
Coronary Syndrome ◽  
Severe Coronary Artery ◽  
Artery Disease ◽  
Living With Hiv ◽  
Missed Diagnoses

The pathophysiology of accelerated atherosclerosis in people living with Human Immunofediciency virus (HIV) is complex. Coronary artery disease (CAD) has become an important cause of mortality in these patients. They often have atypical symptoms, leading to frequently missed diagnoses. We report a case of a 51-year-old male undergoing antiretroviral therapy who was admitted for acute coronary syndrome. He had severe coronary artery disease that involved difficult management.

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