MMP Polymorphisms and Acute Coronary Syndromes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00484406
Recruitment Status : Completed
First Posted : June 8, 2007
Last Update Posted : June 8, 2007
Information provided by:
University of Trieste

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).

Condition or disease
Unstable Angina

Detailed Description:

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 infarction and progression of coronary stenosis. In MMP-9 a more complex polymorphism involves a microsatellite (AC) repeat in position –90 to –131. The mechanism leading to increased MMP-9 expression is probably related to the transition to Z-DNA within the microsatellite, which eases transcription. In vitro studies show that the longer the tandem repeats sequence, the higher the transcription.

No studies on metalloproteinase polymorphism in NSTEACS have been carried out, so far.

This study has been planned to assess if patients admitted to the hospital for NSTEACS could be associated to a different in hospital clinical outcome according to the genetic polymorphism of these proteases.

Study Type : Observational
Observational Model: Defined Population
Primary Purpose: Screening
Time Perspective: Longitudinal
Time Perspective: Prospective
Official Title: Matrix Metalloproteinase Genetic Polymorphisms and Outcome of Non-ST Elevated Acute Coronary Syndromes
Study Start Date : February 2005
Actual Study Completion Date : May 2007

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • non ST elevation acute coronary syndrome (NSTE ACS)

Exclusion Criteria:

  • STE acute myocardial infarction

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00484406

Azienda per i Servizi Sanitari n.6 "FRIULI OCCIDENTALE"
Pordenone, Italy
Clinica Medica - University of Trieste
Trieste, Italy, 34149
Sponsors and Collaborators
University of Trieste
Principal Investigator: Nicola FIOTTI, MD University of Trieste, ITALY
Study Chair: Carlo Giansante, MD University of Trieste, ITALY

Publications automatically indexed to this study by Identifier (NCT Number): Identifier: NCT00484406     History of Changes
Other Study ID Numbers: FT-05-CG-201040106
First Posted: June 8, 2007    Key Record Dates
Last Update Posted: June 8, 2007
Last Verified: May 2007

Keywords provided by University of Trieste:
Matrix Metalloproteinases
Genetic polymorphism
Acute coronary syndromes

Additional relevant MeSH terms:
Acute Coronary Syndrome
Angina, Unstable
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Angina Pectoris
Chest Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms