Aldehyde dehydrogenase 2-associated metabolic abnormalities and cardiovascular diseases: current status, underlying mechanisms, and clinical recommendations

Abstract

Abstract. Cardiovascular diseases originate from various pathogeneses, among which metabolic abnormalities are common. An integrated metabolic disturbance in common cardiovascular diseases has been suggested, particularly in the Asian population. This speculation is supported by the finding that aldehyde dehydrogenase 2 (ALDH2) gene mutations are present in nearly half of the Asian population. ALDH2 mutations significantly reduce ALDH2 enzyme activity and increase production of toxic aldehydes, including 4-hydroxynonenal, and are involved in the pathophysiology of several cardiovascular disorders such as atherosclerosis and myocardial infarction. Additionally, individuals with ALDH2 mutations are more susceptible to hypertension and diabetes, and these mutations are significantly correlated with heart failure. Until now there are no actionable clinical recommendations with regards to screening for ALDH2 mutations. A comprehensive understanding of the relationship between ALDH2 and these etiologies may greatly help in better prevention and treatment of cardiovascular diseases in populations, especially Asian, where ALDH2 mutations are common.