Matrix metalloproteinases are responsible for degradation and remodelling of extracellular matrix and exert important roles in initiation and progression of inflammatory diseases. We aimed to examine the role of Matrix metalloproteinases (MMPs) and their regulators in degenerative arterial diseases. Serum samples were collected from patients with arterial disease (n = 126), who underwent surgery because of symptomatic aorto‐occlusive disease (AOD, n = 18), carotid artery stenosis (n = 67) or abdominal arotic aneurysm (n = 41). Serum MMP‐1, MMP‐8, MMP‐13, TIMP‐1, myeloperoxidase (MPO) and neutrophil elastase (HNE) concentrations were determined by ELISA, and the molar ratio of MMP‐8 and TIMP‐1 was calculated. To get reference values, the determinations were done on samples of healthy blood donors (n = 100). In univariate analyses, the patients had higher MMP‐8 (P < 0.001), TIMP‐1 (P = 0.045), and MMP‐8/TIMP‐1 (P < 0.001), and lower MPO (P < 0.001) when compared with the blood donors. All three subgroups had higher MMP‐8 (P < 0.001) and MMP‐8/TIMP‐1 (P < 0.001), and lower MPO (P < 0.01, except AOD) levels when compared with the references. In multiple logistic regression analyses, the male gender (P < 0.01), age (P < 0.001), elevated MMP‐8 (P < 0.001) and decreased MPO (P < 0.001) concentrations associated significantly with the risk for arterial disease, and provided an area under curve (AUC) of 0.97 in the Receiver operating characteristics analyses. In multiple linear regression analyses, HNE correlated with both MMP‐8 (P < 0.001) and MPO (P = 0.008) concentrations. Combination of high MMP‐8 and low MPO level in serum eventually reflecting selectively modified neutrophil degranulation may indicate increased risk for arterial disease.
Aiming to study the role of human major histocompatibility complex (MHC) region on coronary artery disease (CAD), we enrolled two separate patient materials and controls. First, heart transplantation recipients (n = 276) were divided into three subgroups according to the severity of atherosclerosis. The human leukocyte antigen (HLA)-A-B-DR haplotype and gene frequencies were compared between groups. Second, patients with acute coronary syndrome (ACS) (n = 100) and healthy controls (n = 74) were assessed by nine genetic MHC markers (HLA-A, HLA-B, HLA-DRB1, LTA+253(a/g), LTA+496(C/T), LTA+633(c/g), LTA+724(C/A), C4A and C4B), and the frequencies were compared. In the heart transplantation recipients, HLA-DR1 was strongly associated with CAD [severe vs no evidence, odds ratio (OR) 2.37; 95% confidence interval (CI) 1.33-4.25; P = 0.003]. Similarly, in the patients with ACS, HLA-DRB1*01 was associated with CAD (patients vs controls, OR 2.36; 95% CI 1.25-4.44; P = 0.007). HLA-DRB1*01 was associated with low-density-lipoprotein cholesterol (OR 5.32; 95% CI 1.64-17.26; P = 0.005) and smoking habit (OR 3.13; 95% CI 1.09-9.03; P = 0.035) as risk factors. The strongest protective gene was HLA-B*07 alone (OR 0.46; 95% CI 0.24-0.88; P = 0.02) or together with the haplotype LTA+253a-LTA+633g-C4A3-C4B1 (OR 0.36; 95% CI 0.22-0.57; P = 0.00001). In conclusion, human MHC region harbors genes that protect from and predispose to CAD.
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