Wang Wenmin, Wang Jizheng, Yao Ke, Wang Shuiyun, Nie Meng, Zhao Yizi, Wang Bohong, Pang Huanhuan, Xu Jingjing, Wu Guixin, Lu Minjie, Tang Nan, Qi Chunmei, Pei Hengzhi, Luo Xufang, Li Dongsheng, Yang Tianshu, Sun Qing, Wei Xiang, Li Yan, Jiang Dingsheng, Li Peng, Song Lei, Hu Zeping
School of Pharmaceutical Sciences, Tsinghua-Peking Center for Life Sciences, Beijing Frontier Research Center for Biological Structure, Tsinghua University, Beijing, China.
Shanghai Qi Zhi Institute, Shanghai, China.
Nat Cardiovasc Res. 2022 May;1(5):445-461. doi: 10.1038/s44161-022-00057-1. Epub 2022 May 9.
Hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease with heterogeneous clinical presentations, governed by multiple molecular mechanisms. Metabolic perturbations underlie most cardiovascular diseases; however, the metabolic alterations and their function in HCM are unknown. Here, we describe the metabolome and lipidome of heart and plasma samples from individuals with and without HCM. Correlation analyses showed strong association between metabolic alterations and cardiac function and prognosis of patients with HCM. Using machine learning we identified metabolite panels as potential HCM diagnostic markers or predictors of survival. Clustering based on metabolome and lipidome of heart enabled stratification of patients with HCM into three subgroups with distinct cardiac function and survival. Integration of metabolomics and proteomics data identified metabolic pathways significantly altered in patients with HCM, with the pentose phosphate pathway and oxidative stress being particularly upregulated. Thus, targeting the pentose phosphate pathway and oxidative stress may serve as potential therapeutic strategies for HCM.
肥厚型心肌病（HCM）是一种常见的遗传性心血管疾病，临床表现多样，受多种分子机制调控。代谢紊乱是大多数心血管疾病的基础；然而，HCM中的代谢改变及其功能尚不清楚。在此，我们描述了患有和未患有HCM的个体心脏和血浆样本的代谢组和脂质组。相关性分析显示，代谢改变与HCM患者的心脏功能和预后密切相关。我们使用机器学习识别出代谢物面板作为潜在的HCM诊断标志物或生存预测指标。基于心脏代谢组和脂质组的聚类能够将HCM患者分为三个具有不同心脏功能和生存情况的亚组。代谢组学和蛋白质组学数据的整合确定了HCM患者中显著改变的代谢途径，其中磷酸戊糖途径和氧化应激尤其上调。因此，针对磷酸戊糖途径和氧化应激可能成为HCM的潜在治疗策略。
