MEDICINE AND HEALTH

Metabolic remodeling research is expected to become a breakthrough in the accurate diagnosis and treatment of hypertrophic cardiomyopathy


Project Design Overview (Provided by Respondents)

“I have just been diagnosed with hypertrophic cardiomyopathy, how long can I live?”

Although hypertrophic cardiomyopathy (HCM) is neither a terminal nor a rare disease, it has a pessimistic feeling in patient groups and forums because of its difficult early diagnosis, poor prognosis, and the primary cause of sudden death in young people.

Medical staff are also suffering HCM for a long time.

In order to study the pathogenesis of HCM more comprehensively from a new perspective other than genetic mutations, Hu Zeping’s team from the School of Pharmacy of Tsinghua University cooperated with the Song Lei team of Fuwai Hospital of the Chinese Academy of Medical Sciences and the Shanghai Zhizhi Research Institute to systematically depict the metabolome and lipidomic maps in the myocardial tissue and plasma of HCM patients, revealing the metabolic remodeling law of HCM patients.

These findings are expected to facilitate the development of HCM treatment options. The related research results “Metabolic Characterization of Human Cardiac Hypertrophic Cardiomyopathy” were published online in the journal Nature-Cardiovascular Research on May 9.

3 biomarkers and potential therapeutic targets were identified

HCM is the most inherited cardiovascular disease, with about 60% of patients carrying the causative gene. “Some families even died suddenly of several young people in succession.” As the deputy director of the Department of Internal Medicine of Fuwai Hospital, Song Lei has experienced too many sorrows and joys in the clinical years, and when he says this, his voice has unconsciously lowered.

For the past 30 years, HCM has been thought to be an autosomal dominant disorder primarily caused by mutations in the sarcomere gene. However, the overall metabolic changes in HCM are understood by the academic community is very limited.

In this regard, Hu Zeping told China Science Daily that he hopes that the research results of HCM metabolic remodeling can promote the solution of clinical problems from the aspects of early diagnosis, prognosis prediction, clinical molecular typing and new therapeutic targets.

In this project, the research team started from the perspective of metabolic research and explained the metabolic remodeling characteristics and laws of HCM. Correlation analysis showed that large amounts of metabolites were significantly associated with cardiac function and survival outcomes in HCM patients. Using machine learning, they identified potential biomarkers that could serve as predictions of early diagnosis and postoperative survival of HCM.

The researchers also suggest in the article that intervening in the pentose phosphate pathway and oxidative stress may become potential therapeutic strategies for HCM.

Big data “asking for directions” for accurate diagnosis and treatment

Studies have found that changes in myocardial metabolism are significantly associated with HCM prognosis and can be used as an indicator of HCM risk stratification.

HCM is the leading cause of sudden death in adolescents and is an important cause of heart failure in middle-aged patients, while stroke is predisposed to elderly patients. Wang Jizheng, a researcher at Fuwai Hospital, is the co-first author and co-corresponding author of the above article, he introduced: “HCM heterogeneity is very strong, each patient’s symptoms and risks are different, whether it is sudden death or heart failure can not be well predicted, is not conducive to precision treatment, patients are also worried, suffering.” ”

The study eventually established a combination of 12 metabolites and lipid group compound metabolites to judge the prognosis of HCM patients.

Several reviewers in the journal Nature Cardiovascular Research have suggested that one of the key advantages of this study is the large sample size cohort of clinical samples in the disease group, as well as the depth and breadth of molecular analysis (metabolites, proteins), as well as reliable AI analysis.

The study analyzed metabolomics and lipidomics of 349 HCM and 16 non-HCM myocardial tissues, and 143 HCM and 60 non-HCM plasma samples.

The omics big data generated by such a large cohort of clinical samples prompted AI technology to play an important role in this study, identifying three biomarkers for HCM diagnosis and prognosis prediction. Hu Zeping believes that the value of artificial intelligence technology in the study of HCM mechanism will become more and more significant.

Clinical and basic research join forces to expand research horizons

Song Lei led the team to complete the world’s largest cardiomyopathy epidemic survey, clarified the prevalence of HCM in Chinese group of 1/500, and his team has built the largest clinical database, specimen library and gene information database of hereditary cardiovascular diseases in China. Hu Zeping’s team has long studied the metabolic abnormalities and mechanisms of cancer, cardiomyopathy, viral infectious diseases and other diseases through the research and development and application of metabolic technology, lipidomics, proteomics, metabolic flow analysis, multi-omics integration analysis and other means.

Song Lei said that he was “recommended by experts in the field” to find Hu Zeping, and the high degree of agreement between them on the goals of HCM led to the 3-and-a-half-year study.

Hu Zeping has always remembered a knot that Song Lei told him, a seventeen or eighteen-year-old HCM patient was very desperate about his condition, his grandfather and father died early at the age of thirty or forty due to HCM, when he asked “how long can he live”, Song Lei felt speechless.

There are also patients who are not allowed to run violently in their teens, who begin to have chest pain, breathing difficulties, syncope and other symptoms at the age of 20, and who have surgery due to atrial fibrillation and heart obstruction at the age of 30, “I don’t know where the hope is, every day is suffering.”

Towards the goal of alleviating the physical and mental pain of patients as soon as possible, hu Zeping and Song Lei hope that the two teams can deepen cooperation in the follow-up, and further explore the pathogenesis mechanism by re-validating HCM patients in a larger population, and further explore the pathogenesis, promote the research and development of new drugs, and achieve early prevention, early diagnosis, early diagnosis, early and precise treatment of HCM as soon as possible. (Source: China Science Daily Zhang Nan)

Related paper information:https://doi.org/10.1038/s44161-022-00057-1



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