title: Biomarkers Associated with Ischemic Stroke in Diabetes Mellitus Patients.
abstract: Diabetes is an established risk factor for ischemic stroke, but the associated molecular mechanisms remain to be fully elucidated. This study investigated the role of plasma and platelet microRNAs and their targeting proteins in the activation of platelets and their association with the occurrence of ischemic stroke in patients with type 2 diabetes mellitus (T2DM). Results showed that the expressions of platelet and plasma miR-144 and miR-223 were significantly altered in T2DM patients with or without ischemic stroke compared to that in healthy controls, but these changes were more significant in T2DM patients with ischemic stroke. The expressions of P2Y12 and IRS-1 as well as phosphorylation levels of IRS-1, PI3K, and Akt in platelets were significantly altered in T2DM patients with or without ischemic stroke. The expression of platelet miR-144 and miR-223 significantly correlated with their plasma levels, P2Y12 and IRS-1 expression, blood glucose concentration, and platelet activation rate. High glucose concentration significantly elevated P-selectin, miR-144 and P2Y12 expression and significantly reduced miR-223 and IRS-1 expression in UT-7 cells. Overexpression of miR-223 and blocking of miR-144 expression significantly normalized the effects of high glucose concentration in UT-7 cells. In conclusion, hyperglycemia may activate platelets through miR-144 and miR-223 to downregulate IRS-1 and upregulate P2Y12 expression in the platelets of T2DM patients through an IRS-1-PI3K-Akt signaling. Low platelet and plasma miR-223 expression in addition to high platelet and plasma miR-144 expression are risk factors for ischemic stroke in T2DM patients.
authors.affiliation: Department of Endocrinology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, People's Republic of China.
authors.forename: Shuisheng
authors.initials: S
authors.lastname: Yang
authors.affiliation: Hepatobiliary Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China.
authors.forename: Jingfeng
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Hepatobiliary Enteric Surgery Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China. chenyx008@aliyun.com.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, People's Republic of China. leimingxiang@yahoo.com.
authors.forename: Minxiang
authors.initials: M
authors.lastname: Lei
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000235:genetics; D005260:Female; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000097:blood; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000097:blood; D010766:Phosphorylation; D015539:Platelet Activation; D051057:Proto-Oncogene Proteins c-akt / Q000097:blood; D058925:Receptors, Purinergic P2Y12 / Q000097:blood; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000209:etiology* / Q000235:genetics; D014162:Transfection
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D055504:Insulin Receptor Substrate Proteins; D035683:MicroRNAs; D019007:P-Selectin; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D058925:Receptors, Purinergic P2Y12; C526292:IRS1 protein, human; C554293:MIRN144 microRNA, human; C525067:MIR223, human; C548576:P2RY12 protein, human; C546937:SELP protein, human
keywords: Diabetes mellitus; Ischemic stroke; Platelet; miR-144; miR-223