IL-17A facilitates platelet function through the ERK2 signaling pathway in patients with acute coronary syndrome.
BACKGROUND
Platelet aggregation mediated by inflammation played a critical role in the development of coronary heart diseases (CHD). Our previous clinical researches showed that Th17 cells and their characteristic cytokine IL-17A were associated with the plaque destabilization in patients with acute coronary syndrome (ACS). However, the potent effect of IL-17A on platelets-induced atherothrombosis remains unknown.


RESULTS
In this study, we detected the plasma IL-17A levels and platelet aggregation in patients with stable angina (SA), unstable angina (UA), acute myocardial infarction (AMI) and chest pain syndrome (CPS). In addition, the markers of platelet activation (CD62P/PAC-1) and the mitogen-activated protein kinases (MAPKs) pathway were detected in platelets from ACS patients. We found that plasma IL-17A levels and platelet aggregation in patients with ACS (UA and AMI) were significantly higher than patients with SA and CPS, and the plasma IL-17A levels were positively correlated with the platelet aggregation (R = 0.47, P<0.01). In addition, in patients with ACS, the platelet aggregation, CD62P/PAC-1 and the phosphorylation of ERK2 signaling pathway were obviously elevated in platelets pre-stimulated with IL-17A in vitro. Furthermore, the specific inhibitor of ERK2 could attenuate platelet aggregation and activation triggered by IL-17A.


CONCLUSIONS
Our experiment firstly proved that IL-17A could promote platelet function in patients with ACS via activating platelets ERK2 signaling pathway and may provide a novel target for antiplatelet therapies in CHD.
Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.
Shuang
S
Zhang
Jing
J
Yuan
Miao
M
Yu
Hong
H
Fan
Zhang-Qiang
ZQ
Guo
Rui
R
Yang
He-Ping
HP
Guo
Yu-Hua
YH
Liao
Min
M
Wang
D054058:Acute Coronary Syndrome / Q000097:blood / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology*; D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000201:enzymology* / Q000502:physiology*; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000097:blood*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology
C508717:IL17A protein, human; D020381:Interleukin-17; D047428:Protein Kinase Inhibitors; D000244:Adenosine Diphosphate; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1