SMAD7 methylation as a novel marker in atherosclerosis

Atherosclerosis is a complicated process comprising inflammation, accumulation of collagen matrix and aberrant DNA methylation. SMAD7 is known to play an important role in fibrosis and inflammation. In recent years, increasing research has concentrated on the connection between DNA methylation and atherosclerosis. The current study was designed to investigate methylation status of some specific gene with a focus on SMAD7 in atherosclerosis and elucidate their relationship. We found that SMAD7 expression was decreased and its promoter region was markedly methylated in atherosclerotic plaques when compared with normal artery walls. Using MALDI-TOF MS, increased DNA methylation levels of SMAD7 promoter at CpG unit 5.8.15.16 were found in peripheral blood of atherosclerosis patients relative to matched normal controls, respectively. Correlation analysis revealed that mean DNA methylation levels of SMAD7 promoter of CpG unit 5.8.15.16 were positively associated with homocysteine levels (r = 0.724, p < .001) and carotid plaque scores(r = 0.790, p < .001). SMAD7 promoter is hyper-methylated both in human atherosclerotic plaques and atherosclerosis patients, which is positively associated with homocysteine levels and carotid plaque scores. Thus, methylated SMAD7 may be a novel predicted marker and therapeutics target for atherosclerosis.