PAR2 (Protease-Activated Receptor 2) Deficiency Attenuates Atherosclerosis in Mice.

Autor:	Jones SM; From the Division of Cardiovascular Health and Disease (S.M.J., A.M., K.C., K.S., L.M.M., N.R., M.T., A.P.O.)., Mann A; From the Division of Cardiovascular Health and Disease (S.M.J., A.M., K.C., K.S., L.M.M., N.R., M.T., A.P.O.)., Conrad K; From the Division of Cardiovascular Health and Disease (S.M.J., A.M., K.C., K.S., L.M.M., N.R., M.T., A.P.O.).; Pathobiology and Molecular Medicine Program (K.C., M.T., A.P.O.)., Saum K; From the Division of Cardiovascular Health and Disease (S.M.J., A.M., K.C., K.S., L.M.M., N.R., M.T., A.P.O.).; University of Cincinnati Medical Scientist Training Program (K.S.)., Hall DE; Department of Nutritional Sciences, College of Allied Health (D.E.H., A.D.P.).; Department of Internal Medicine (D.E.H., A.D.P.), University of Cincinnati College of Medicine, OH., McKinney LM; From the Division of Cardiovascular Health and Disease (S.M.J., A.M., K.C., K.S., L.M.M., N.R., M.T., A.P.O.)., Robbins N; From the Division of Cardiovascular Health and Disease (S.M.J., A.M., K.C., K.S., L.M.M., N.R., M.T., A.P.O.)., Thompson J; Division of Endocrinology and Molecular Medicine, Department of Internal Medicine, University of Kentucky, Lexington (J.T.)., Peairs AD; Department of Nutritional Sciences, College of Allied Health (D.E.H., A.D.P.).; Department of Internal Medicine (D.E.H., A.D.P.), University of Cincinnati College of Medicine, OH., Camerer E; INSERM U970, Paris Cardiovascular Research Centre, France (E.C.)., Rayner KJ; Department of Biochemistry, Microbiology, and Immunology, University of Ottawa Heart Institute, Ontario, Canada (K.J.R.)., Tranter M; From the Division of Cardiovascular Health and Disease (S.M.J., A.M., K.C., K.S., L.M.M., N.R., M.T., A.P.O.).; Pathobiology and Molecular Medicine Program (K.C., M.T., A.P.O.)., Mackman N; Division of Hematology and Oncology, Department of Medicine, UNC McAllister Heart Institute, University of North Carolina at Chapel Hill (N.M.)., Owens AP 3rd; From the Division of Cardiovascular Health and Disease (S.M.J., A.M., K.C., K.S., L.M.M., N.R., M.T., A.P.O.) phillip.owens@uc.edu.; Pathobiology and Molecular Medicine Program (K.C., M.T., A.P.O.).
Jazyk:	angličtina
Zdroj:	Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2018 Jun; Vol. 38 (6), pp. 1271-1282. Date of Electronic Publication: 2018 Mar 29.
DOI:	10.1161/ATVBAHA.117.310082
Abstrakt:	Objective: PAR2 (protease-activated receptor 2)-dependent signaling results in augmented inflammation and has been implicated in the pathogenesis of several autoimmune conditions. The objective of this study was to determine the effect of PAR2 deficiency on the development of atherosclerosis. Approach and Results: PAR2 mRNA and protein expression is increased in human carotid artery and mouse aortic arch atheroma versus control carotid and aortic arch arteries, respectively. To determine the effect of PAR2 deficiency on atherosclerosis, male and female low-density lipoprotein receptor-deficient ( Ldlr -/- ) mice (8-12 weeks old) that were Par2 +/+ or Par2 -/- were fed a fat- and cholesterol-enriched diet for 12 or 24 weeks. PAR2 deficiency attenuated atherosclerosis in the aortic sinus and aortic root after 12 and 24 weeks. PAR2 deficiency did not alter total plasma cholesterol concentrations or lipoprotein distributions. Bone marrow transplantation showed that PAR2 on nonhematopoietic cells contributed to atherosclerosis. PAR2 deficiency significantly attenuated levels of the chemokines Ccl2 and Cxcl1 in the circulation and macrophage content in atherosclerotic lesions. Mechanistic studies using isolated primary vascular smooth muscle cells showed that PAR2 deficiency is associated with reduced Ccl2 and Cxcl1 mRNA expression and protein release into the supernatant resulting in less monocyte migration. Conclusions: Our results indicate that PAR2 deficiency is associated with attenuation of atherosclerosis and may reduce lesion progression by blunting Ccl2 - and Cxcl1 -induced monocyte infiltration. (© 2018 American Heart Association, Inc.)
Databáze:	MEDLINE
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