title: Clopidogrel, a platelet P2Y12 receptor inhibitor, reduces vascular inflammation and angiotensin II induced-abdominal aortic aneurysm progression.
abstract: 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.
authors.affiliation: Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Ou
authors.initials: O
authors.lastname: Liu
authors.forename: Lixin
authors.initials: L
authors.lastname: Jia
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Liu
authors.forename: Yueli
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Wang
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Qin
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.forename: Hongjia
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000502:physiology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001795:Blood Pressure Determination; D000077144:Clopidogrel; D016207:Cytokines / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D058925:Receptors, Purinergic P2Y12 / Q000737:chemistry* / Q000378:metabolism; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014657:Vasculitis / Q000378:metabolism / Q000517:prevention & control*; D014662:Vasoconstrictor Agents / Q000633:toxicity
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D010975:Platelet Aggregation Inhibitors; D017382:Reactive Oxygen Species; D058925:Receptors, Purinergic P2Y12; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000077144:Clopidogrel; D020782:Matrix Metalloproteinases; D013988:Ticlopidine