title: TLR3 and TLR4 as potential clinically biomarkers of cardiovascular risk in coronary artery disease (CAD) patients.
abstract: Coronary artery disease (CAD), as a lipid-driven and inflammation-driven disease, has threatened thousands of patients' lives. Toll-like receptors, the most characterized innate immune receptors, have recently been demonstrated to play a key role in coronary artery disease, particularly Toll-like receptor (TLR) 3 and TLR4. We examined TLR3, TLR4, and associated inflammatory factors expression in monocytes and their signaling pathway proteins in patients with varying degrees of coronary artery atherosclerosis [group S (single diseased vessel), n = 36; group D (double diseased vessels), n = 36; group T (three diseased vessels), n = 33 compared with controls (n = 35)]. In mononuclear cells, TLR3 mRNA and protein, and IRF-3 were significantly down-regulated as the coronary arteries stenosis number increased. However, TLR4 mRNA and protein, and MyD88 were significantly increased in patients with coronary artery stenosis compared with controls, and were associated with the number of stenoses. In serum, there was significant up-regulation in TNF-α, IL-8, and MCP-1 and obvious down-regulation in INF-β and IP-10 with severity of CAD. This study demonstrates differential expression of TLR3 and TLR4 at both the mRNA and protein level in both mononuclear cells and downstream serum readouts of patients with CAD compared with the control. The expression of TLR4 and TLR3 closely correlated with the severity of coronary artery disease as reflected by the number of coronary artery stenoses. TLR3 and TLR4 have the potential to be a clinically useful biomarker of cardiovascular risk.
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an, 710061, Shaanxi, People's Republic of China, shaoliang021224@hotmail.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Shao
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qun
authors.initials: Q
authors.lastname: Lu
authors.forename: Aiqun
authors.initials: A
authors.lastname: Ma
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D023921:Coronary Stenosis / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D053594:Myeloid Differentiation Factor 88 / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood; D012307:Risk Factors; D012720:Severity of Illness Index; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000097:blood* / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000097:blood* / Q000235:genetics
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; C495344:TLR3 protein, human; C495345:TLR4 protein, human; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4