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

Autor: Emanuela Falcinelli, Giovanni Cimmino, Gianluca Petrillo, Plinio Cirillo, Paolo Golino, Francesco Loffredo, Massimo Ragni, Massimo Chiariello, Paolo Gresele
Přispěvatelé: Cimmino, Giovanni, Ragni, M, Cirillo, P, Petrillo, G, Loffredo, F, Chiariello, M, Greselep, Falcinelli, E, Golino, Paolo, Cimmino, G, Cirillo, Plinio, Gresele, P, Golino, P.
Rok vydání: 2013
Předmět:
Zdroj: International Journal of Cardiology. 168:981-986
ISSN: 0167-5273
DOI: 10.1016/j.ijcard.2012.10.040
Popis: 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.
Databáze: OpenAIRE