Relation of baseline plasma MMP-1 levels to long-term all-cause mortality in patients with known or suspected coronary artery disease referred for coronary angiography

Abstract

Objectives To investigate the long-term prognostic significance of baseline plasma MMP-1 levels in a group of well-characterized male patients with known or suspected coronary artery disease, including those presenting with the acute coronary syndrome. Background MMP-1 is an interstitial collagenase that is considered the primary enzyme responsible for collagen degradation. In addition, MMP-1 can lead to platelet activation through the PAR1 pathway that is independent of thrombin. Methods Baseline plasma MMP-1 levels were measured in 364 male patients who were referred for coronary angiography and followed prospectively for the development of all-cause mortality for 5 years. Results After adjustment for a variety of baseline clinical, angiographic and laboratory parameters, baseline plasma MMP-1 levels (analyzed as a continuous variable) was an independent predictor of all-cause mortality at 5 years (HR, 1.49; 95% CI, 1.23-1.80; P<0.0001). Furthermore, in 3 additional multivariate models that included a wide variety of contemporary biomarkers with established prognostic efficacy (i.e., ST2, GDF-15, cystatin C, hs-CRP, myeloperoxidase, TIMP-1, adiponectin, RDW, hemoglobin, erythropoietin), MMP-1 remained an independent predictor of all-cause mortality at 5 years. Similar results were obtained when the analyses were restricted to the subpopulation of patients presenting with acute coronary syndrome. Conclusions Elevated levels of MMP-1 are associated with an increased risk of long-term all-cause mortality in patients with known or suspected coronary disease that is independent of a variety of clinical, angiographic, laboratory variables, including a whole host of contemporary biomarkers with established prognostic efficacy representing multiple different pathophysiologic processes.

Metalloproteinases in atherosclerosis

“…Furthermore, elevated plasma levels of MMP-1 (Cavusoglu et al 2015) and MMP-8 (Djurić et al 2010, Momiyama et al 2010 have been detected in patients with atherosclerosis, while no association was detected for plasma levels of MMP-13 (Momiyama et al 2010). Finally, elevated intra-plaque and plasma levels of MMP-8 are predictive for systemic cardiovascular events (Peeters et al 2011) and subsequent all-cause mortality (Cavusoglu et al 2015), respectively.…”

Matrix Metalloproteinase-1 Gene Polymorphism Associated with Ultrasound-Assessed Carotid Thickness among Older Adults

“…Increased MMP1 expression in the early stages of an atherosclerotic process may be a compensatory response that involves tissue remodeling under physiological stress to delay the progression to thromboembolic events [ 26 ]. However, one cannot ignore the hypothesis that MMP1 plays a pathophysiological role via excessive accumulation as a result of smooth muscle cell accumulation in a necrotic core under a fibrous cap where it weakens high-stress regions [ 6 ], predisposing the plaque to rupture [ 4 , 27 ]. Despite this hypothesis, MMP1 activation is essential for vascular wall remodeling to prevent excessive growth of the intima layer in response to lesions mainly by migration or reprogramming of vascular smooth muscle cells.…”

Biomarkers of Cardiovascular Disease

“…Кроме того, ММР1 способна активировать тромбоциты. Таким образом, при атеросклерозе и его осложнениях ММР1 играет патогенную роль через два разных, но дополняющих друг друга механизма -деградация матрикса сосудистой стенки и активация тромбоцитов, индуцирующая прокоагулянтное состояние [15].…”