ALDH2 Enzyme Deficiency in Diabetic Cardiomyopathy
Abstract
Diabetic cardiomyopathy (DCM) is a significant complication of diabetes, particularly affecting East Asian populations with a high prevalence of the ALDH2*2 (Glu504Lys) genetic variant. This variant impairs aldehyde detoxification, leading to increased oxidative stress, mitochondrial dysfunction, and chronic inflammation, exacerbating cardiac damage and fibrosis. This review aimed to systematically delineate the pathological role of ALDH2 enzyme deficiency in DCM by integrating clinical observations with mechanistic insights from experimental models and evaluating emerging therapies for genetically susceptible populations. In vitro and in vivo studies demonstrate that ALDH2*2 amplifies oxidative stress and disrupts mitochondrial homeostasis under hyperglycemic conditions, leading to enhanced cardiac fibrosis and functional decline. Additionally, ALDH2*2 carriers show heightened susceptibility to metabolic stress, further aggravating DCM. Given the high prevalence of ALDH2*2 in East Asian populations, targeted therapeutic strategies are urgently needed. Promising approaches include ALDH2 activators (e.g., Alda-1) that enhance detoxification of reactive aldehydes, and SGLT2 inhibitors (e.g., empagliflozin) that improve mitochondrial function and reduce oxidative damage. These therapies can mitigate oxidative stress and preserve cardiac function in ALDH2*2 carriers, thereby potentially reducing DCM burden, especially in high-risk East Asian populations. Further clinical…
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