{"database":"iProX","file_versions":[],"scores":null,"additional":{"omics_type":["Proteomics"],"submitter":["Zhuofeng Lin"],"species":["Mus Musculus"],"full_dataset_link":["http://www.iprox.org/page/project.html?id=IPX0008506000"],"submitter_email":["zhuofenglin@wmu.edu.cn"],"submitter_affiliation":["Wenzhou Medical University"],"sample_protocol":[""],"repository":["iProX"],"data_protocol":[""],"pubmed_abstract":["Fibroblast growth factor 21 (FGF21), a metabolic hormone with pleiotropic effects, is beneficial for various cardiac disorders. However, FGF21's role in heart failure with preserved ejection fraction (HFpEF) remains unclear. Here, we show that elevated circulating FGF21 levels are negatively associated with cardiac diastolic function in patients with HFpEF. Global or adipose FGF21 deficiency exacerbates cardiac diastolic dysfunction and damage in high-fat diet (HFD) plus N<sup>[w]</sup>-nitro-L-arginine methyl ester (L-NAME)-induced HFpEF mice, whereas these effects are notably reversed by FGF21 replenishment. Mechanistically, FGF21 enhances the production of adiponectin (APN), which in turn indirectly acts on cardiomyocytes, or FGF21 directly targets cardiomyocytes, to negatively regulate pyruvate dehydrogenase kinase 4 (PDK4) production by activating PI3K/AKT signals, then promoting mitochondrial bioenergetics. Additionally, APN deletion strikingly abrogates FGF21's protective effects against HFpEF, while genetic PDK4 inactivation markedly mitigates HFpEF in mice. Thus, FGF21 protects against HFpEF via fine-tuning the multiorgan crosstalk among the adipose, liver, and heart.","Patients with metabolic dysfunction-associated steatotic liver disease (MASLD), especially advanced metabolic dysfunction-associated steatohepatitis (MASH), have an increased risk of cardiovascular diseases (CVDs). Whether CVD events will, in turn, influence the pathogenesis of MASLD remains unknown. Here, we show that myocardial infarction (MI) accelerates hepatic pathological progression of MASLD. Patients with MASLD who experience CVD events after their diagnosis exhibit accelerated liver fibrosis progression. MI promotes hepatic fibrosis in mice with MASH, accompanied by elevated circulating Ly6C<sup>hi</sup> monocytes and their recruitment to damaged liver tissues. These adverse effects are significantly abrogated when deleting these cells. Meanwhile, MI substantially increases circulating and cardiac periostin levels, which act on hepatocytes and stellate cells to promote hepatic lipid accumulation and fibrosis, finally exacerbating hepatic pathological progression of MASH. These preclinical and clinical results demonstrate that MI alters systemic homeostasis and upregulates pro-fibrotic factor production, triggering cross-disease communication that accelerates hepatic pathological progression of MASLD."],"pubmed_title":["Myocardial infarction accelerates the progression of MASH by triggering immunoinflammatory response and induction of periosti.","FGF21 protects against HFpEF by improving cardiac mitochondrial bioenergetics in mice."],"pubmed_authors":["Xie Wei W, Gan Jing J, Zhou Xiaodong X, Tian Huiying H, Pan Xingchao X, Liu Wenyue W, Li Xiaokun X, Du Jie J, Xu Aimin A, Zheng Minghua M, Wu Fan F, Li Yuling Y, Lin Zhuofeng Z","Zhang Ke K, Gan Jing J, Wang Baile B, Lei Wei W, Zhen Dong D, Yang Jie J, Wang Ningrui N, Wen Congcong C, Gao Xiaotang X, Li Xiaokun X, Xu Aimin A, Liu Xinguang X, Li Yulin Y, Wu Fan F, Lin Zhuofeng Z"],"additional_accession":[]},"is_claimable":false,"name":"DIA proteomics analysis of mice in models of myocardial infarction and heart failure with preserved ejection fraction (HFpEF).","description":"The dataset includes two parts: a) Proteomics of mouse heart tissue 14 days after myocardial infarction and long-term exercised mice post-myocardial infarction for 14 days; b) Cardiac proteomics of a model of heart failure with preserved ejection fraction (HFpEF) induced by L-NAME and high-fat diet-fed wild-type mice, as well as adeno-associated virus-mediated FGF21 overexpression mice and control groups.","dates":{"publication":"Fri Apr 05 00:00:00 GMT+01:00 2024"},"accession":"PXD051242","cross_references":{"TAXONOMY":["10090"],"pubmed":["38838640","39955281"]}}