Impact and potential mechanism of effects of chronic moderate alcohol consumption on cardiac function in aldehyde dehydrogenase 2 gene heterozygous mice

Abstract

Background Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a key enzyme in alcohol metabolism. The ALDH2*2 mutations are found in approximately 45% of East Asians, with 40% being heterozygous (HE) ALDH2*1/*2 and 5% homozygous (HO) ALDH2*2/*2. Studies have shown that HO mice lack cardioprotective effects induced by moderate alcohol consumption. However, the impact of moderate alcohol consumption on cardiac function in HE mice is unknown. Methods In this study, HO, HE, and wild‐type (WT) mice were subjected to a 6‐week moderate alcohol drinking protocol, following which myocardial tissue and cardiomyocytes of the mice were extracted. Results We found that moderate alcohol exposure did not increase mortality, myocardial fibrosis, apoptosis, or inflammation in HE mice, which differs from the effects observed in HO mice. After exposure to the 6‐week alcohol drinking protocol, there was impaired cardiac function, cardiomyocyte contractility, and intracellular Ca2+ homeostasis and mitochondrial function in both HE and HO mice as compared to WT mice. Moreover, these animals showed overt oxidative stress production and increased levels of the activated forms of calmodulin‐dependent protein kinase II (CaMKII) and ryanodine receptor type 2 (RYR2) phosphorylation protein. Conclusion We found that moderate alcohol exposure impaired cardiac function in HE mice, possibly by increasing reactive oxygen species (ROS)/CaMKII/RYR2‐mediated Ca2+ handling abnormalities. Hence, we advocate that people with ALDH2*1/*2 genotypes rigorously avoid alcohol consumption to prevent potential cardiovascular harm induced by moderate alcohol consumption.

Integrative Analysis of Single-Cell and Bulk RNA Sequencing Reveals Prognostic Characteristics of Macrophage Polarization-Related Genes in Lung Adenocarcinoma

“… 82 Moreover, TTN expression has been shown to be related to CTSH, 83 while Hu et al demonstrated that mice with ALDH2 mutations had higher levels of phosphorylated RYR2 protein than wild-type mice. 84 …”

“…82 Moreover, TTN expression has been shown to be related to CTSH, 83 while Hu et al demonstrated that mice with ALDH2 mutations had higher levels of phosphorylated RYR2 protein than wild-type mice. 84 To better understand how characteristic genes affect immune function, a CIBERSORT analysis was performed to assess the differences in immune infiltration between high-and low-risk groups. The results showed significant differences in 11 types of immune cell infiltration between the two groups, with certain immune cells being more abundant in the high-risk group.…”