Bone Marrow-Derived Tenascin-C Attenuates Cardiac Hypertrophy by Controlling Inflammation.
Bone Marrow-Derived Tenascin-C Attenuates Cardiac Hypertrophy by Controlling Inflammation.
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DOI：
10.1016/j.jacc.2017.07.789
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发表时间：
2017-09-26
影响因子：
24
通讯作者：
Sharifi BG
中科院分区：
文献类型：
--
作者：
Song L;Wang L;Li F;Yukht A;Qin M;Ruther H;Yang M;Chaux A;Shah PK;Sharifi BG
TnC(Tenascin-C)是一种高度保守的基质细胞蛋白，在发育和疾病过程中有不同的表达模式。压力超负荷导致左心室(LV)重构导致胎儿基因程序的重新表达。本研究的目的是探讨TNC在压力超负荷所致心肌肥厚中的作用。TNC基因敲除小鼠和野生型小鼠通过缩窄腹主动脉或注射血管紧张素II诱导压力超负荷，采用超声心动图、免疫染色、流式细胞仪、实时定量聚合酶链式反应和骨髓移植等方法评价TNC基因敲除小鼠和野生型小鼠对TNC缺乏症的影响。对压力超负荷心脏的超声心动图分析显示，与野生型小鼠相比，TNC缺陷小鼠的所有LV参数(LV舒张末和收缩末期内径、射血分数和短轴缩短率)都恶化了。在无TNC的情况下，心肌细胞的大小和胶原沉积明显增加。在机制上，TNC缺乏促进CCR2+/Ly6chi单核/巨噬细胞亚群快速积聚到心肌中，以响应压力超负荷。此外，对受体心脏的超声心动图和免疫组织化学分析表明，TNC在骨髓中的表达，而不是在心肌中的表达，保护心肌免受压力超负荷心脏的过度重构。TNC缺乏进一步损害了对压力超负荷反应的心功能，并通过增强炎症而加剧了纤维化。此外，TNC在骨髓中的表达，而不是在心肌中的表达，可以保护心肌免受因轻度压力超负荷而过度重构的影响。
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. The aim of this study was to investigate the function of TNC in cardiac hypertrophy in response to pressure overload. Pressure overload was induced in TNC knockout and wild-type mice by constricting their abdominal aorta or 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. Echocardiographic analysis of pressure overloaded hearts revealed that all LV parameters (LV end-diastolic and end-systolic dimensions, ejection fraction, and fractional shortening) deteriorated in TNC-deficient mice compared to their wild-type counterparts. The size of cardiomyocytes and collagen accumulation were significantly higher in the absence of TNC. Mechanistically, TNC deficiency promoted rapid accumulation of the CCR2+/Ly6Chi 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. 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.
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DOI：
10.1083/jcb.139.1.279
发表时间：
1997-10-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Jones PL;Crack J;Rabinovitch M
通讯作者：
Rabinovitch M
DOI：
10.1146/annurev-pathol-020712-163930
发表时间：
2013-01-24
期刊：
Annual review of pathology
影响因子：
--
作者：
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通讯作者：
Wynn TA
DOI：
10.1073/pnas.85.2.339
发表时间：
1988-01-01
影响因子：
11.1
作者：
IZUMO, S;NADALGINARD, B;MAHDAVI, V
通讯作者：
MAHDAVI, V
DOI：
10.1073/pnas.93.8.3509
发表时间：
1996-04-16
影响因子：
11.1
作者：
Boudreau, N;Werb, Z;Bissell, MJ
通讯作者：
Bissell, MJ
影响因子：
2.9
作者：
Imanaka-Yoshida, K;Matsumoto, K;Yoshida, T
通讯作者：
Yoshida, T