C-reactive protein induces expression of matrix metalloproteinase-9: A possible link between inflammation and plaque rupture

• Published in: International journal of cardiology 2013-09, Vol.168 (2), p.981-986
• Main Authors: Cimmino, Giovanni, Ragni, Massimo, Cirillo, Plinio, Petrillo, Gianluca, Loffredo, Francesco, Chiariello, Massimo, Gresele, Paolo, Falcinelli, Emanuela, Golino, Paolo
• Format: Article
• Language: English
• Subjects: Acute Coronary Syndrome - enzymology; Acute Coronary Syndrome - genetics; Acute Coronary Syndrome - metabolism; Acute coronary syndromes; Aged; Biological and medical sciences; C-Reactive Protein - metabolism; C-Reactive Protein - physiology; Cardiology. Vascular system; Cardiovascular; Cells, Cultured; Coronary heart disease; CRP; Female; Gene Expression Regulation, Enzymologic; Heart; Humans; Inflammation - enzymology; Inflammation - genetics; Inflammation - metabolism; Male; Matrix Metalloproteinase 9 - biosynthesis; Matrix Metalloproteinase 9 - genetics; Medical sciences; Middle Aged; MMP-9; Muscle, Smooth, Vascular - enzymology; Muscle, Smooth, Vascular - metabolism; Myocarditis. Cardiomyopathies; Myocytes, Smooth Muscle - enzymology; Myocytes, Smooth Muscle - pathology; Plaque, Atherosclerotic - blood; Plaque, Atherosclerotic - enzymology; Plaque, Atherosclerotic - metabolism; Up-Regulation - genetics
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2012.10.040

Abstract Background Matrix metalloproteases (MMPs) have been implicated in the pathogenesis of acute coronary syndromes (ACS). However, little is known about the mechanisms responsible for MMP expression in ACS. C-reactive protein (CRP) not only is an independent risk factor for cardiovascular events, but also may exert direct pro-atherosclerotic effects. Therefore, we aimed at determining whether CRP might induce MMP-9 in two different experimental conditions: 1) smooth muscle cells (SMCs) in vitro, and 2) patients with ACS. Methods and results Effects of increasing concentrations of CRP on MMP-9 expression were evaluated in vitro in human SMCs. TIMP-1 protein expression, the selective inhibitor of MMP-9, was also evaluated. CRP dose-dependently induced MMP-9 expression in SMCs by promoting MMP-mRNA transcription, as well as MMP-9 secretion. In contrast, no differences were found for TIMP-1 protein expression. In vivo, MMP-9 and CRP levels were measured in blood samples obtained from the aorta (Ao) and the coronary sinus (Cs) of patients with normal coronary arteries (controls, n = 21), stable angina (n = 24), and ACS (n = 30). Both MMP-9 and CRP plasma levels were significantly increased across the coronary circulation only in patients with ACS. Interestingly, a significant correlation between MMP-9 and CRP plasma levels was found. Conclusions CRP induced MMP-9 expression and activity in human SMCs in culture; patients presenting with ACS have increased transcoronary plasma levels of MMP-9 and CRP with a significant correlation between these two markers. This may explain the heightened risk of coronary events in subjects with elevated levels of CRP.