MMP Polymorphisms and Acute Coronary Syndromes

This study has been completed.
Sponsor:
Information provided by:
University of Trieste
ClinicalTrials.gov Identifier:
NCT00484406
First received: June 7, 2007
Last updated: NA
Last verified: May 2007
History: No changes posted
  Purpose

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
Unstable Angina

Study Type: Observational
Study Design: Observational Model: Defined Population
Primary Purpose: Screening
Time Perspective: Longitudinal
Official Title: Matrix Metalloproteinase Genetic Polymorphisms and Outcome of Non-ST Elevated Acute Coronary Syndromes

Resource links provided by NLM:


Further study details as provided by University of Trieste:

Study Start Date: February 2005
Study Completion Date: May 2007
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • non ST elevation acute coronary syndrome (NSTE ACS)

Exclusion Criteria:

  • STE acute myocardial infarction
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00484406

Locations
Italy
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
Investigators
Principal Investigator: Nicola FIOTTI, MD University of Trieste, ITALY
Study Chair: Carlo Giansante, MD University of Trieste, ITALY
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00484406     History of Changes
Other Study ID Numbers: FT-05-CG-201040106
Study First Received: June 7, 2007
Last Updated: June 7, 2007
Health Authority: Italy: Ethics Committee

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

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

ClinicalTrials.gov processed this record on July 20, 2014