The role of aldehyde dehydrogenase 2 in cardiovascular disease.

Jian Zhang, Yunyun Guo, Xiangkai Zhao, Jiaojiao Pang, Chang Pan, Jiali Wang, Shujian Wei, Xiao Yu, Cheng Zhang, Yuguo Chen, Huiyong Yin, Feng Xu

Journal: Nature reviews. Cardiology 2023;20(7):495-509

PMID: 36781974

Full Text on Nature Publishing Group View on PubMed

Abstract

Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme involved in the detoxification of alcohol-derived acetaldehyde and endogenous aldehydes. The inactivating ALDH2 rs671 polymorphism, present in up to 8% of the global population and in up to 50% of the East Asian population, is associated with increased risk of cardiovascular conditions such as coronary artery disease, alcohol-induced cardiac dysfunction, pulmonary arterial hypertension, heart failure and drug-induced cardiotoxicity. Although numerous studies have attributed an accumulation of aldehydes (secondary to alcohol consumption, ischaemia or elevated oxidative stress) to an increased risk of cardiovascular disease (CVD), this accumulation alone does not explain the emerging protective role of ALDH2 rs671 against ageing-related cardiac dysfunction and the development of aortic aneurysm or dissection. ALDH2 can also modulate risk factors associated with atherosclerosis, such as cholesterol biosynthesis and HDL biogenesis in hepatocytes and foam cell formation and efferocytosis in macrophages, via non-enzymatic pathways. In this Review, we summarize the basic biology and the clinical relevance of the enzymatic and non-enzymatic, tissue-specific roles of ALDH2 in CVD, and discuss the future directions in the research and development of therapeutic strategies targeting ALDH2. A thorough understanding of the complex roles of ALDH2 in CVD will improve the diagnosis, management and prognosis of patients with CVD who harbour the ALDH2 rs671 polymorphism.

Address: Department of Emergency Medicine, Chest Pain Center, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Shandong, China.; Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Shandong, China.; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Shandong, China.; Key Laboratory Experimental Teratology of the Ministry of Education, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shandong University, Shandong, China.; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Shandong, China.; Department of Cardiology, Qilu Hospital of Shandong University, Shandong, China.; Department of Emergency Medicine, Chest Pain Center, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Shandong, China. [email protected].; Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Shandong, China. [email protected].; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Shandong, China. [email protected].; Chinese Academy of Sciences Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Innovation Center for Intervention of Chronic Disease and Promotion of Health, Chinese Academy of Sciences, Shanghai, China. [email protected].; School of Life Science and Technology, ShanghaiTech University, Shanghai, China. [email protected].; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China. [email protected].; Department of Emergency Medicine, Chest Pain Center, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Shandong, China. [email protected].; Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Shandong, China. [email protected].; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Shandong, China. [email protected].

DOI: 10.1038/s41569-023-00839-5

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https://doi.org/10.1038/s41569-023-00839-5

MeSH Terms: Humans, Cardiovascular Diseases, Aldehyde Dehydrogenase, Mitochondrial, Polymorphism, Genetic, Coronary Artery Disease, Aldehydes, Ethanol