{"database":"iProX","file_versions":[],"scores":null,"additional":{"omics_type":["Proteomics"],"submitter":["Xingzhong Zhang"],"species":["Mus Musculus"],"full_dataset_link":["http://www.iprox.org/page/project.html?id=IPX0016604000"],"submitter_email":["zhangxingzhong@fuwai.com"],"submitter_affiliation":["Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University"],"sample_protocol":[""],"repository":["iProX"],"data_protocol":[""],"pubmed_abstract":["Hyperhomocysteinemia (HHcy) is an independent risk factor for thrombotic cardiovascular events. We previously demonstrated that homocysteine (Hcy) amplifies platelet activation by promoting membrane remodeling and enhancing signaling through surface platforms such as integrin αIIbβ3 and G protein-coupled receptors. However, the mechanisms by which Hcy remodels platelet membrane lipid metabolism remain poorly understood. Here, using an integrated proteomic and lipidomic approach, we showed that Hcy disrupted platelet lipid homeostasis by impairing fatty acid β-oxidation (FAO), a metabolic pathway that depends on the coordinated action of peroxisomes and mitochondria. Proteomic profiling showed that Hcy downregulated peroxisome proliferator-activated receptor α (PPARα) and its downstream targets carnitine palmitoyltransferase 1 and 2 (CPT1/2), while lipidomic analysis confirmed the accumulation of medium and long-chain fatty acids, which promoted platelet reactive oxygen species production and mitochondrial dysfunction. Notably, pharmacological activation of PPARα with fenofibrate, a PPARα agonist, restored FAO in a CPT1/2-dependent manner, remodeled the platelet lipid membrane, and attenuated Hcy-potentiated platelet hyperactivation and thrombus formation. Collectively, these findings suggest a previously unrecognized Hcy-PPARα-FAO axis in platelet function and thrombosis, linking impaired peroxisomal and mitochondrial FAO to platelet hyperactivation, and support restoring membrane phospholipid dysregulation as a potential therapeutic strategy for HHcy-promoted thrombotic diseases."],"pubmed_title":["Fenofibrate attenuates hyperhomocysteinemia-potentiated thrombosis by restoring platelet fatty acid β-oxidation."],"pubmed_authors":["Han Lulu L, Du Xing X, Yan Yu Y, Zhang Linqi L, Feng Juan J, Wang Xian X, Zhang Xingzhong X"],"additional_accession":[]},"is_claimable":false,"name":"The platelet proteomic data treated with Hcy","description":"Platelets were isolated from C57BL6/J (C57) mice following established methodology detailed in our prior publication23. In brief, whole blood was collected via the inferior vena cava from C57BL/6J mice (aged 6–8 weeks) under anesthesia induced by 2.5% tribromoethanol (200 mg/kg).  Then, an unbiased protein profiling analysis was conducted on the platelets after homocysteine intervention.","dates":{"publication":"Thu Apr 09 00:00:00 GMT+01:00 2026"},"accession":"PXD076844","cross_references":{"TAXONOMY":["10090"],"pubmed":["42251786"]}}