Abstract-Matrix metalloproteinase 9 (MMP9) is expressed in human atherosclerotic plaques, and the protein is localized in human coronary atherosclerotic lesions. The MMP9 gene has a C-to-T promoter polymorphism at position Ϫ1562, which affects transcription and leads to promoter low-activity (C/C) and high-activity (C/T, T/T) genotypes. To determine whether these genotypes exert an influence on the atherosclerotic lesion area, we investigated their association with different types of coronary lesions in an autopsy cohort of 276 men aged 33 to 69 years. Areas of the coronary wall covered with fatty streaks and fibrotic, calcified, and complicated lesions were measured, and the percentage of coronary narrowing was determined. MMP9 genotypes were determined by polymerase chain reaction and restriction enzyme digestion. In men aged Ն53 years, the mean area of complicated lesions in 3 coronaries was significantly associated with the MMP9 genotype (Pϭ0.008). Subjects with high promoter activity genotypes had, on average, larger complicated lesion areas than did those with the low-activity genotype. The MMP9 genotype persisted as an independent predictor of complicated lesion area after adjustment for age, body mass index, hypertension, diabetes, and smoking (Pϭ0.012). These data provide evidence that the proposed effect of MMP9 in the process of atherosclerotic lesion development may be modified by the MMP9 genotype. Key Words: matrix metalloproteinase 9 Ⅲ coronary artery disease Ⅲ complicated lesions Ⅲ genetics Ⅲ polymorphism T he matrix metalloproteinases (MMPs), among them MMP9 (also known as gelatinase B and 92-kDa type IV collagenase), constitute a family of enzymes required for the degradation of extracellular matrix during embryonic development, morphogenesis, and tissue remodeling. MMP3 (stromelysin 1), MMP1 (interstitial collagenase), and MMP9 (92-kD gelatinase) are present and enzymatically active in atherosclerotic plaques and are known to be associated with the progression and development of atherosclerotic lesions. 1,2 The MMP family consists of Ն15 metal-dependent endopeptidases with activity against most extracellular matrix macromolecules.MMP9 has recently been identified in human atherosclerotic lesions. 2,3 It is active against denatured collagens (gelatin) and type IV, V, and XI collagens in addition to the proteoglycans and elastin also found in atherosclerotic lesions. 4 MMP9 expression is primarily regulated at the transcription level, with the promoter of the gene responding to different growth factors and cytokines. 5 Zhang et al 6 have found a functional MMP9 gene promoter C-to-T polymorphism at position Ϫ1562, which affects gene transcription and yields promoter low-activity (C/C) and high-activity (C/T, T/T) genotypes. 6 They also observed an association between this polymorphism and the severity of angiographically measured atherosclerosis.No data are as yet available on the impact of the MMP9 genotypes at the vessel-wall level in respect to the coronary complicated lesion area and plaque r...
