| Backgroud Increasing evidences indicate that aldehyde dehydrogenase 2 (ALDH2) is as a key enzyme of cytoprotection for the cardiovascular diseases, such as coronary heart disease, hypertension, heart failure, ischemia reperfusion injury and so on. However, the mechanism is still not clear.Objective This study was to investigate the role and mechanism of ALDH2 on progress of atherosclerosis from both clinical setting and basic research via the protection against endoplasmic reticulum stress (ERS).Methods Total 248 patients with coronary heart disease were recruited after being diagnosed by cardioangiography. They were divided into two groups according to ALDH2 genotype (ALDH2 wild type group and ALDH2 mutation group). Baseline clinical characteristics, coronary angiography, coronary artery Gensini score were recorded and calculated. Blood serum 4-HNE was detected by ELISA method. To mimic atherosclerosis model, smooth muscle cells were treated by oxLDL (150μg/ml) in vitro. SMC were incubated Alda-1 (20μM, ALDH2 activiting agent), Daidzin (120μM, ALDH2 inhibitor), adenovirus transfection of ALDH2 were also applied as the intervention agents. Apoptosis was evaluated by flow cytometry, and TUNEL staining. Protein expressions of GRP78, PERK, p-eIF2α, ATF-4, CHOP,4-HNE were determined by Western blot.Results1.84 patients with ALDH2 mutation and 164 patients with ALDH2 wild type were recruited. Statistical differences were found in drinking history (26.2%vs7.1%, P<0.001).2. The number of stent (0.89±1.29 vs 1.34±1.6, P<0.05) and Gensini score (23.43±24.47 vs 33.12<033.39, P±.05).3. Multicategory logistic regression showed that hypertension (OR=3.241) and ALDH2 mutant type (OR=2.295) were risk factors for coronary heart disease.4.4-HNE was significant increased in the ALDH2 mutant group compared with wild type group (20.43±5.87 vsl4.47±5.16).5. Western blot analysis showed that the protein levels of GRP78, PERK, p-eIF2a, ATF-4, CHOP,4-HNE in smooth muscle cells were elevated by oxLDL, which were alleviated by Alda-1 or aggravated by Daidzin.6. Cell apoptosis induced by oxLDL could be attenuated by Alda-1, enhanced by Daidzin as shown through flow cytometry, TUNEL staining and CCK-8 assay.Conclusions1. ALDH2 gene polymorphism is closely related to atherosclerosis and stenosis severity of coronary artery.2. ALDH2 gene mutation is an independent risk factor for coronary heart disease.3. The ability of ALDH2 mutation to remove 4-HNE was lower.4. ALDH2 palliates the progression of atherosclerosis via attenuating ERS and apoptosis in smooth muscle cells. |
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