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Diabetes drugs may reduce coronary artery disease in people with “Asian brilliance”.news center
The team then tested the ability of blood vessels to expand, or the performance of endothelial cells, by tracking blood flow. A finger-fitting device was used to test study participants immediately before and after they drank alcohol. “This study showed that vasodilation was significantly impaired in people with the variant, even one drink of him, but not in those without the variant,” said an instructor at the Institute of Cardiovascular Medicine. said the paper’s lead author, Dr. Hongchao Guo.
The group then used genetically modified human induced pluripotent stem cells to create ALDH2-deficient endothelial cells in Petri dishes. These revealed increased cell damage due to oxidative stress and inflammation, and decreased production of vaso-relaxing nitric oxide compared to cells without deficiency. All three of these alterations represent ways in which ALDH2 variants harm or disable endothelial cells, he said. Additionally, all of these detrimental effects were amplified when alcohol was added to the mix.
look for medicine
Finally, the team performed a computational molecular search for compounds that might compensate for the lack of ALDH2. They found empagliflozin, a drug already commonly used to treat diabetes, to be suitable. They tested it in a mouse model of diabetes with alcohol exposure and ALDH2 deficiency. I was.
The team returned to the lab to identify the mechanisms behind the diabetes drug’s benefits. They administered empagliflozin to her ALDH2-deficient human endothelial cells and confirmed that the drug reduced the amount of cellular oxidative damage and inflammation. It also increases nitric oxide production, and in all the right places he roughly compensates for his ALDH2 deficiency.
“Empagliflozin does not alleviate alcohol flushes because it targets the downstream pathway of ALDH2*2 rather than directly stimulating ALDH2 activity. *2 It may be used in high-risk patients such as carriers,” said Wu.
Wu would like to see clinical trials examining whether ALDH2 deficiency and alcohol consumption exacerbate endothelial dysfunction in patients with diabetes or pre-existing coronary artery disease. “If this is confirmed, the patient will be better informed to reduce alcohol consumption in general and to avoid drinking alcohol if possible, especially for her ALDH2 carriers (those who exhibit alcoholic flushes). We should be able to tell,” he said, Wu.
“Additionally, ALDH2 variants are associated with an increased risk of atrial fibrillation in chronic drinkers, which is one of the most common types of arrhythmia,” said Wu. “We are investigating the role of alcohol-induced arrhythmias in ALDH2 carriers using a patient-specific induced pluripotent stem cell model.”
Wu said his overall message is simple. If you’re not drinking, don’t start. “
Researchers at Greenstone Biosciences contributed to this study.
This work was supported by the National Institutes of Health (K99 HL150319, K99 HL150216, R01 AA11147, R35 GM119522, R01 HL130020, R01 HL126527, R01 HL113006, R01 HL146690, P01 HL146690, P01 HL141084, Tobacco-Related Heart Disease and the American Heart Association). Supported. research program.
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Sources 2/ https://med.stanford.edu/news/all-news/2023/01/alcohol-metabolize-heart-disease.html The mention sources can contact us to remove/changing this article |
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