Inflammatory unbalance of TLR3 and TLR4 in PCI patients with or without type 2 diabetes mellitus.
BACKGROUND
Toll-like receptors, the most characterized innate immune receptors, have recently been demonstrated to play an important role in coronary atherosclerotic disease and diabetes mellitus (DM). TLR3 and TLR4 are known to act as anti-inflammatory and pro-inflammatory factors respectively in multi-factorial inflammatory disease states. However, there is less research about TLR3 and TLR4 expression in percutaneous transluminal coronary intervention (PCI) patients, particularly those with type 2 diabetes mellitus (DM2).


METHODS
We examined TLR3 and TLR4 expression and their downstream signaling pathway in PCI patients with (n=31) or without (n=32) DM2 compared with controls (n=35).


RESULTS
TLR3 and downstream anti-inflammatory factors (IRF-3, INF-β and IL-10) were significantly down-regulated in PCI patients with or without DM2 compared with controls, as determined by the quantification of both mRNA and protein. In contrast, TLR4 and downstream proinflammatory factors (MyD88 and TNF-α) were up-regulated in PCI patients with or without DM2 compared with controls.


CONCLUSIONS
Patients undergoing PCI were shown to have a TLR-dependent pro-inflammatory state, mediated by a downregulation of TLR3 pathway, and upregulation of TLR4. This occurred in both with or without type 2 diabetes mellitus compared with controls in this research. The inflammatory imbalance observed in PCI patients was exacerbated in patients with DM2, consistent with a likely contribution of DM2 to the inflammatory state of coronary atherosclerotic disease, via impact on the innate immune response. This data supports the potential of TLRs as a novel therapeutic target in diabetics with coronary atherosclerotic disease.
Department of Cardiovascular Medicine, the First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Institute of Cardiovascular Channelopathy, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Shaanxi Province, No. 277 Yanta West Road, Xi'an, Shaanxi 710061, PR China; Key Laboratory of Molecular Cardiology, Shaanxi Province, No. 277 Yanta West Road, Xi'an, Shaanxi 710061, PR China.
Liang
L
Shao
Department of Neurology, Union Hospital of Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, PR China.
Ping
P
Zhang
First Department of Cardiology, Shaanxi Provincial People's Hospital, Third Affiliated Hospital of Medical College of Xi'an Jiaotong University, No. 256 Friendship Road, Xi'an, Shaanxi 710061, PR China.
Yong
Y
Zhang
Department of Cardiovascular Medicine, the First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Institute of Cardiovascular Channelopathy, Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Shaanxi Province, No. 277 Yanta West Road, Xi'an, Shaanxi 710061, PR China; Key Laboratory of Molecular Cardiology, Shaanxi Province, No. 277 Yanta West Road, Xi'an, Shaanxi 710061, PR China. Electronic address: maaiqun@medmail.com.cn.
Aiqun
A
Ma
D015906:Angioplasty, Balloon, Coronary; D003324:Coronary Artery Disease / Q000150:complications* / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000175:diagnosis; D005260:Female; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4
Inflammatory unbalance; Percutaneous transluminal coronary intervention; Toll-like receptors; Type 2 mellitus diabetes