Bone Marrow-Derived Tenascin-C Attenuates Cardiac Hypertrophy by Controlling Inflammation

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:70

Article

Song, Lei¹  Wang, Lai¹  Li, Fuqiang¹  Yukht, Ada¹  Qin, Minghui¹  Ruther, Haley¹  Yang, Mingjie¹  Chaux, Aurelio¹  Shah, Prediman K.¹  Sharifi, Behrooz G.¹ 

[1] Cedars Sinai Heart Inst, Oppenheimer Atherosclerosis Res Ctr, Los Angeles, CA USA

关键词: left ventricle;    macrophage;    pressure overload;    tenascin;   

DOI  :  10.1016/j.jacc.2017.07.789

来源: Elsevier

【 摘 要 】

BACKGROUND Tenascin-C (TNC) is a highly conserved matricellular protein with a distinct expression pattern during development and disease. Remodeling of the left ventricle (LV) in response to pressure overload leads to the re-expression of the fetal gene program. OBJECTIVES The aim of this study was to investigate the function of TNC in cardiac hypertrophy in response to pressure overload. METHODS Pressure overload was induced in TNC knockout and wild-type mice by constricting their abdominal aorta or by infusion of angiotensin II. Echocardiography, immunostaining, flow cytometry, quantitative real-time polymerase chain reaction, and reciprocal bone marrow transplantation were used to evaluate the effect of TNC deficiency. RESULTS Echocardiographic analysis of pressure overloaded hearts revealed that all LV parameters (LV end-diastolic and -systolic dimensions, ejection fraction, and fractional shortening) deteriorated in TNC-deficient mice compared with their wild-type counterparts. Cardiomyocyte size and collagen accumulation were significantly greater in the absence of TNC. Mechanistically, TNC deficiency promoted rapid accumulation of the CCR2(+)/Ly6C(hi) monocyte/macrophage subset into the myocardium in response to pressure overload. Further, echocardiographic and immunohistochemical analyses of recipient hearts showed that expression of TNC in the bone marrow, but not the myocardium, protected the myocardium against excessive remodeling of the pressure-overloaded heart. CONCLUSIONS TNC deficiency further impaired cardiac function in response to pressure overload and exacerbated fibrosis by enhancing inflammation. In addition, expression of TNC in the bone marrow, but not the myocardium, protected the myocardium against excessive remodeling in response to mild pressure overload. (C) 2017 by the American College of Cardiology Foundation.

【 授权许可】

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