Ignite Creation Date:
2024-05-05 @ 5:35 PM
Last Modification Date:
2024-10-26 @ 9:33 AM
Study NCT ID:
NCT00484406
Status:
COMPLETED
Last Update Posted:
2007-06-08
First Post:
2007-06-07
Brief Title:
MMP Polymorphisms and Acute Coronary Syndromes
Sponsor:
University of Trieste
Organization:
University of Trieste
Study Overview
Official Title:
Matrix Metalloproteinase Genetic Polymorphisms and Outcome of Non-ST Elevated Acute Coronary Syndromes
Status:
COMPLETED
Status Verified Date:
2007-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 GG- at -1563 for MMP-1 4A5A- 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
It is conceivable that these polymorphisms correlate with the clinical outcome of acute coronary syndromes particularly with those without ST segment Elevation NSTEACS
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 21000 subjectsyear 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
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None