Profilin-1 is involved in macroangiopathy induced by advanced glycation end products via vascular remodeling and inflammation  

作　　者：Zhi-Lin Xiao Li-Ping Ma Da-Feng Yang Mei Yang Zhen-Yu Li Mei-Fang Chen 

机构地区：[1]Department of Geriatric Cardiology,National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Central South University,Changsha 410008,Hunan Province,China [2]Department of Cardiology,Shandong Provincial Qianfoshan Hospital,Shandong University,Jinan 250014,Shandong Province,China [3]Department of Cardiovascular Surgery,The Second Xiangya Hospital,Central South University,Changsha 410011,Hunan Province,China

出　　处：《World Journal of Diabetes》2021年第11期1875-1893,共19页世界糖尿病杂志（英文版）（电子版）

基　　金：the National Natural Science Foundation of China,No.81000140,No.81770358,and No.82000339;Natural Science Foundation of Hunan Province,No.2017JJ3486;and the Fund for Health Care in Hunan Province,No.B2017-01.

摘　　要：BACKGROUND The accumulation of advanced glycation end products(AGEs)have been implicated in the development and progression of diabetic vasculopathy.However,the role of profilin-1 as a multifunctional actin-binding protein in AGEs-induced atherosclerosis(AS)is largely unknown.AIM To explore the potential role of profilin-1 in the pathogenesis of AS induced by AGEs,particularly in relation to the Janus kinase 2(JAK2)and signal transducer and activator of transcription 3(STAT3)signaling pathway.METHODS Eighty-nine individuals undergoing coronary angiography were enrolled in the study.Plasma cytokine levels were detected using ELISA kits.Rat aortic vascular smooth muscle cells(RASMCs)were incubated with different compounds for different times.Cell proliferation was determined by performing the MTT assay and EdU staining.An AGEs-induced vascular remodeling model was established in rats and histological and immunohistochemical analyses were performed.The mRNA and protein levels were detected using real-time PCR and Western blot analysis,respectively.In vivo,shRNA transfection was performed to verify the role of profilin-1 in AGEs-induced proatherogenic mediator release and aortic remodeling.Statistical analyses were performed using SPSS 22.0 software.RESULTS Compared with the control group,plasma levels of profilin-1 and receptor for AGEs(RAGE)were significantly increased in patients with coronary artery disease,especially in those complicated with diabetes mellitus(P<0.01).The levels of profilin-1 were positively correlated with the levels of RAGE(P<0.01);additionally,the levels of both molecules were positively associated with the degree of coronary artery stenosis(P<0.01).In vivo,tail vein injections of AGEs induced the release of proatherogenic mediators,such as asymmetric dimethylarginine,intercellular adhesion molecule-1,and the N-terminus of procollagen III peptide,concomitant with apparent aortic morphological changes and significantly upregulated expression of the profilin-1 mRNA and protein in the thoracic a

关 键 词：Advanced glycation end products Profilin-1 Diabetic macroangiopathy ATHEROSCLEROSIS Vascular remodeling Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway 

分 类 号：R587.2[医药卫生—内分泌]