Clinical Trial: MMP Polymorphisms and Acute Coronary Syndromes
Study Status: Completed
Recruit Status: Completed
Study Type: Observational
Official Title: Matrix Metalloproteinase Genetic Polymorphisms and Outcome of Non-ST Elevated Acute Coronary Syndromes
Brief Summary:
Some Matrix Metalloproteases, proteases degrading the extracellular matrix, play a relevant role in structure and stability of atherosclerotic plaques. Atherosclerotic plaques triggering acute coronary syndromes show increased expression of MMP-1, MMP-3 and MMP-9. Regulation of these MMPs is plaid by genetic polymorphisms, G+/G- at –1563 for MMP-1, 4A/5A- at –1612 for MMP-3, and a microsatellite (13-27 CA repeats around –90) for MMP-9.
It is conceivable that these polymorphisms correlate with the clinical outcome of acute coronary syndromes, particularly with those without ST segment Elevation (NSTEACS).
Detailed Summary:
Non-ST elevation acute coronary syndrome (NSTEACS) is a syndrome encompassing a spectrum of clinical manifestations between ischemic heart disease and acute myocardial infarction. It represents an important cause of morbidity and hospitalization in western countries: its incidence is estimated around 2/1000 subjects/year and about 10% of patients with acute coronary syndrome develop an acute myocardial infarction within 6 months. Another reason of concern is that patients require an invasive treatment, usually PTCA or CABG. ACS encompasses features of both an inflammatory and thrombotic disease; their abnormalities could be critical for evolution and complication of acute coronary syndrome.
Many inflammatory and coagulation indicators have been investigated, although the critical factors responsible for complications in NSTEACS remain elusive.
Matrix remodeling and consequent erosion or fissuration of the unstable plaque is supposed to be a key step of the development of acute coronary syndromes.
Neutral matrix metalloproteinases 1, 3 and 9 have been demonstrated to be actively produced in atherosclerotic tissue, compared to unaffected arteries. Mechanisms responsible for such increased expression might be related to inflammation, but also genetic regulation could account for an increased expression leading to a different clinical outcome of the syndrome.
Genetic polymorphisms are described for all three MMPs involved in ACS. MMP-1 insertion of a G in position creates an ets binding site that induces an eight times increase of the synthesis rate. For MMP-3 (stromelysin) polymorphism, a deletion of an A (adenosine) in position -1171 doubles the transcription activity and has been recently associated with acute myocardial infa
Sponsor: University of Trieste
Current Primary Outcome:
Original Primary Outcome:
Current Secondary Outcome:
Original Secondary Outcome:
Information By: University of Trieste
Dates:
Date Received: June 7, 2007
Date Started: February 2005
Date Completion:
Last Updated: June 7, 2007
Last Verified: May 2007
