Matrix metalloproteinases: implication in vascular matrix remodelling during atherogenesis.
1. The matrix metalloproteinases are a family of at least 16 zinc-dependent endopeptidases possessing catalytic activity against extracellular matrix components. Some members of this family have been implicated in vascular matrix remodelling in the pathogenesis of atherosclerosis. 2. A common, naturally occurring variant has been identified in the promoter of the stromelysin gene with one allele having a run of five adenosines (5A) and the other having six adenosines (6A). Functional analyses have shown that the 6A allele has a lower promoter activity than the 5A allele, which is probably attributable to preferential binding of a putative transcriptional repressor protein. 3. In patients with coronary artery disease, the 6A allele has been found to be associated with progression of atherosclerosis assessed by sequential quantitative angiography. 4. In conclusion, the matrix metalloproteinases may be over-expressed in certain locations in atherosclerotic plaques, which might contribute to local destruction of connective tissue and thus plaque rupture. In the majority of lesional areas, however, matrix synthesis is likely to outstrip matrix degradation, because matrix accumulation is a major feature of most atheromas. This imbalance favouring matrix deposition is likely to be exacerbated in individuals with the 6A6A genotype in whom stromelysin expression is lower due to the weaker stromelysin promoter.
Ye
S
S
Department of Cardiovascular Medicine, University of Oxford, U.K.
Humphries
S
S
Henney
A
A
D000483:Alleles; D001161:Arteriosclerosis / Q000201:enzymology* / Q000235:genetics; D005109:Extracellular Matrix / Q000201:enzymology*; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D008666:Metalloendopeptidases / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*
D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3