Clopidogrel, a platelet P2Y12 receptor inhibitor, reduces vascular inflammation and angiotensin II induced-abdominal aortic aneurysm progression

• Published in: PloS one Vol. 7; no. 12; p. e51707
• Main Authors: Liu, Ou, Jia, Lixin, Liu, Xiaoxi, Wang, Yueli, Wang, Xiaolong, Qin, Yanwen, Du, Jie, Zhang, Hongjia
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.12.2012; Public Library of Science (PLoS)
• Subjects: Abdomen; Aneurysm; Aneurysms; Angiogenesis; Angiotensin; Angiotensin II; Angiotensin II - toxicity; Angiotensins; Animal models; Animal tissues; Animals; Aorta; Aortic Aneurysm, Abdominal - chemically induced; Aortic Aneurysm, Abdominal - metabolism; Aortic Aneurysm, Abdominal - prevention & control; Aortic aneurysms; Apolipoprotein E; Apolipoproteins; Apolipoproteins E - physiology; Biology; Blood clots; Blood platelets; Blood Platelets - drug effects; Blood Platelets - metabolism; Blood Pressure Determination; Bone marrow; Clopidogrel; Coronary vessels; Cytokines; Cytokines - metabolism; Degeneration; Education; Heart surgery; Hospitals; Immunoenzyme Techniques; In vivo methods and tests; Incubation; Infiltration; Inflammation; Inflammation - metabolism; Inflammation - prevention & control; Inhibitors; Laboratory animals; Lymphocytes; Lymphocytes T; Macrophages; Macrophages, Peritoneal - cytology; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - metabolism; Matrix metalloproteinases; Matrix Metalloproteinases - metabolism; Medicine; Mice; Mice, Inbred C57BL; Mice, Knockout; Platelet Aggregation Inhibitors - pharmacology; Platelets; Reactive Oxygen Species - metabolism; Receptors, Purinergic P2Y12 - chemistry; Receptors, Purinergic P2Y12 - metabolism; Stress analysis; T cells; Ticlopidine - analogs & derivatives; Ticlopidine - pharmacology; Transplants & implants; Vascular diseases; Vasculitis - metabolism; Vasculitis - prevention & control; Vasoconstrictor Agents - toxicity; Beijing China; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0051707

Medial degeneration and inflammation are features of abdominal aortic aneurysms (AAAs). However, the early inflammatory event initiating aneurysm formation remains to be identified. Activated platelets release abundant proinflammatory cytokines and are involved in initial inflammation in various vascular diseases. We investigated the role of platelets in progression of AAA in vivo and in vitro. Histological studies of tissues of patients with AAA revealed that the number of platelets was increased in aneurysm sites along with the increased infiltration of T lymphocytes and augmented angiogenesis. In a murine model of AAA, apolipoprotein E-knockout mice infused with 1,000 ng/kg/min angiotensin II, treatment with clopidogrel, an inhibitor of platelets, significantly suppressed aneurysm formation (47% decrease, P<0.05). The clopidogrel also suppressed changes in aortic expansion, elastic lamina degradation and inflammatory cytokine expression. Moreover, the infiltration of macrophages and production of matrix metalloproteinases (MMPs) were also significantly reduced by clopidogrel treatment. In vitro incubation of macrophages with isolated platelets stimulated MMP activity by 45%. These results demonstrate a critical role for platelets in vascular inflammation and AAA progression.