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Cardiovascular Drugs and Therapy

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Open Access 01-12-2013 | ORIGINAL ARTICLE

Inhibition of Platelet Activation by Clopidogrel Prevents Hypertension-Induced Cardiac Inflammation and Fibrosis

Authors: Li-Xin Jia, Guan-Ming Qi, Ou Liu, Tao-Tao Li, Min Yang, Wei Cui, Wen-Mei Zhang, Yong-Fen Qi, Jie Du

Published in: Cardiovascular Drugs and Therapy | Issue 6/2013

Abstract

Purpose

Platelets are essential for primary hemostasis; however, platelet activation also plays an important proinflammatory role. Inflammation promotes the development of cardiac fibrosis and heart failure induced by hypertension. In this study, we aimed to determine whether inhibiting platelet activation using clopidogrel could inhibit hypertension-induced cardiac inflammation and fibrosis.

Methods

Using a mouse model of angiotensin II (Ang II) infusion (1,500 ng/[kg·min] for 7 days), we determined the role of platelet activation in Ang II infusion-induced cardiac inflammation and fibrosis using a P2Y₁₂ receptor inhibitor, clopidogrel (50 mg/[kg·day]).

Results

CD41 staining showed that platelets accumulated in Ang II-infused hearts. Clopidogrel treatment inhibited Ang II infusion-induced accumulation of α-SMA⁺ myofibroblasts and cardiac fibrosis (4.17 ± 1.26 vs. 1.46 ± 0.81, p < 0.05). Infiltration of inflammatory cells, including Mac-2⁺ macrophages and CD45⁺Ly6G⁺ neutrophils (30.38 ± 4.12 vs. 18.7 ± 2.38, p < 0.05), into Ang II-infused hearts was also suppressed by platelet inhibition. Real-time PCR and immunohistochemical staining showed that platelet inhibition significantly decreased the expression of interleukin-1β and transforming growth factor-β. Acute injection of Ang II or PE stimulated platelet activation and platelet-leukocyte conjugation, which were abolished by clopidogrel treatment.

Conclusion

Thus, inhibition of platelet activation by clopidogrel prevents cardiac inflammation and fibrosis in response to Ang II. Taken together, our results indicate Ang II infusion-induced hypertension stimulated platelet activation and platelet-leukocyte conjugation, which initiated inflammatory responses that contributed to cardiac fibrosis.

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Title: Inhibition of Platelet Activation by Clopidogrel Prevents Hypertension-Induced Cardiac Inflammation and Fibrosis
Authors: Li-Xin Jia
Guan-Ming Qi
Ou Liu
Tao-Tao Li
Min Yang
Wei Cui
Wen-Mei Zhang
Yong-Fen Qi
Jie Du
Publication date: 01-12-2013
Publisher: Springer US
Published in: Cardiovascular Drugs and Therapy / Issue 6/2013
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI: https://doi.org/10.1007/s10557-013-6471-z

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Inhibition of Platelet Activation by Clopidogrel Prevents Hypertension-Induced Cardiac Inflammation and Fibrosis

Abstract

Purpose

Methods

Results

Conclusion

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