遗传性心脏病,蛋白质 z-bo 2020-10-09 319

　　Hypertrophic cardiomyopathy is the most common inherited heart disease. It is characterized by an abnormal thickening of the heart muscle, which can block blood flow and cause sudden death in young people. Previous studies have shown that as many as 1,400 gene mutations can cause the disease, but in a new study, scientists at the University of Wisconsin-Madison found that hypertrophic cardiomyopathy is the most serious. When it is found in patients with different symptoms, many different gene mutations can cause changes in myocardial protein. This shared protein fingerprint shows that universal therapies can be designed to treat diseases caused by various genetic mutations.

　　related results were recently published in "PNAS" magazine. Professor Inge and graduate students Trisha Tucholski and Cai Wenxuan of the University of Wisconsin-Madison led the research and used advanced protein measurement techniques to analyze disease and normal hearts in detail. Protein properties. In particular, the author collected samples of affected heart tissue from 16 patients who underwent corrective surgery to repair impaired blood flow to the heart. Due to eight different mutations between the two genes, eight of the patients had hypertrophic cardiomyopathy. The genetic mutation that causes the disease in the other eight patients is not yet known. The authors then compared the protein composition of patient heart samples and healthy donor heart samples. Although the underlying genetic mutations are different, the authors found a common pattern of heart mutations in patients suffering from it. For example, many important muscle proteins from the diseased heart have low phosphate molecular tags. The exact result of reducing phosphate is not yet known, but these altered proteins can cause general damage to the heart, leading to diseased muscle thickening.

　　Using a mouse model, the authors have previously demonstrated that cardiac troponin I mutations (Gly203Ser: cTnI-G203S) are associated with increased mitochondrial metabolic activity. This is consistent with the situation of human patients. In this study, the authors studied the effects of cardiac L-type calcium channel (AID-TAT) alpha-derived peptides on mice with cardiac abnormalities due to related mutations. The results show that the treatment can effectively restore mitochondrial metabolic activity and prevent cardiac hypertrophy. In vivo multispectral imaging system is used for evaluation. The authors found that the six protein intermediates in the heart of cTnI-G203S mutant mice had abnormal changes, but mice with definite cardiomyopathy did not have the above characteristics. It is well known that the above-mentioned proteins can restore the mitochondrial membrane potential of cardiomyocytes and the oxidation of flavoprotein and prevent cardiomyocyte hypertrophy. In addition, AID-TAT therapy can quickly target the heart and prevent it from being trapped in the liver or kidneys. Overall, the authors determined the HCM biomarker changes caused by the Gly203Ser mutation, and proposed safe and preventive treatments for cardiomyopathy. In "high-risk" patients with Gly203Ser gene mutations, the use of AID-TAT to regulate cardiometabolic activity may be beneficial in preventing HCM. This finding further proves that genetic mutations are not always sufficient to explain the outbreak of the disease.

　　"When we first performed these experiments, the similarity of protein levels surprised us because it is generally believed that different mutations cause different changes in protein. But in fact, these results make sense. When patients with this disease go During hospital operations, their hearts will also experience similar dysfunction.