CityUHK researchers unveil the mystery of "Asian Flush" mechanism, pioneering new directions in precision treatment for heart attacks

HONG KONG, March 12, 2026 /PRNewswire/ --  Approximately 40% of the East Asian population suffers from alcohol intolerance, commonly known as "Asian Flush Syndrome". This ALDH2 genetic mutation is more than just a metabolic defect; it conceals a deadly cardiovascular risk. While the medical community has long observed that carriers of this mutation suffer more severe heart damage during a myocardial infarction (heart attack), the specific underlying mechanism has remained a mystery until now.

A research team led by Professor Yin Huiyong, Professor in the Department of Biomedical Sciences at City University of Hong Kong (CityUHK), recently published a groundbreaking study in Circulation, a top-tier journal in cardiovascular medicine. Titled "ALDH2/eIF3E Interaction Modulates Protein Translation Critical for Cardiomyocyte Ferroptosis in Acute Myocardial Ischemia Injury", the research reveals for the first time how the ALDH2 mutation triggers "ferroptosis"—a specific type of cell death—during heart attacks, leading to a rapid deterioration of cardiac tissue. This discovery opens new doors for precision prevention and treatment for hundreds of millions of gene carriers worldwide.

The study highlights that the ALDH2 mutation does not only impair alcohol metabolism but also significantly worsens heart damage during acute myocardial infarction. The team carried out a clinical study of 177 Chinese patients with acute heart failure, and found that those carrying the ALDH2 mutation exhibited much more severe cardiac dysfunction following a heart attack. In this study, the team observed clear signs of ferroptosis in these patients, including a significant drop in Coenzyme Q10 (a cardio-protective antioxidant) and a massive accumulation of bioactive lipids that cause oxidative damage to cells.

Ferroptosis is a form of cell death driven by iron ions and lipid peroxidation. For the heart, this death process acts like a chain reaction, delivering an irreversible and devastating blow to myocardial cells, eventually leading to severe acute heart failure.

The key scientific breakthrough of this study lies in identifying the ALDH2 protein's hidden role as a cellular "regulator". Under normal conditions, ALDH2 binds with the eIF3E subunit (part of the complex responsible for protein synthesis), acting like a "security lock" to maintain protein balance within the cell. However, in the presence of the ALDH2 mutation, structural changes cause this lock to fail. The released eIF3E then enters a "selective mode", prompting ribosomes to mass-produce pathogenic proteins that induce ferroptosis. This role reversal—from a "metabolic enzyme" to a "translational regulator"—explains why individuals with the "flushing gene" suffer significantly more heart damage when facing the same level of myocardial ischemia.

To verify these mechanisms and identify therapeutic opportunities, the team conducted experiments using animal models. The results demonstrated that either inhibiting the ferroptosis process via medication or using genetic technology to regulate the protein translation pathway could significantly improve heart function in mice carrying the ALDH2 mutation after a heart attack. This suggests that existing iron chelators or specific ferroptosis inhibitors have immense potential to be developed into protective therapies specifically for East Asian populations.

The study redefines the physiological role of ALDH2 in cardiac protection and underscores the vital importance of precision medicine in treating cardiovascular diseases. In the future, clinicians may be able to use genetic testing to identify high-risk ALDH2 carriers and implement "anti-ferroptosis" interventions early to predict and improve outcomes for heart attack patients.

Other institutions participating in this joint study include Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, the Naval Medical University, Sun Yat-sen University, Fudan University, and Harbin Medical University. The research was supported by the National Natural Science Foundation of China, the Shenzhen Medical Research Fund, the Research Grants Council of Hong Kong, and CityUHK.

The global impact of this research is further highlighted by a dedicated editorial commentary in the same issue of Circulation. Entitled "Selective mRNA Translation: A New Player in Ferroptosis After Myocardial Infarction", the piece is authored by Professor Yi Zhu, a renowned scientist in the cardiovascular field from Tianjin Medical University. Such a commentary is a significant honour, reserved for studies that provide transformative insights and open new frontiers in medical science.