压力过载
医学
纤维化
肌肉肥大
内科学
藤黄蛋白C
心肌纤维化
收缩性
基质金属蛋白酶
心室重构
内分泌学
心脏病学
心力衰竭
免疫组织化学
心肌肥大
作者
Bruno K. Podesser,Maximilian Kreibich,Elda Dzilic,David Santer,Lorenz Förster,S Trojanek,Dietmar Abraham,Martin Krs̆s̆ák,Klaus Ulrich Klein,Eva Verena Tretter,Christoph Kaun,Johann Wojta,Barbara Kapeller,Inês Gonçalves,Karola Trescher,Attila Kiss
标识
DOI:10.1097/hjh.0000000000001628
摘要
Aims: Left ventricular (LV) hypertrophy is characterized by cardiomyocyte hypertrophy and interstitial fibrosis ultimately leading to increased myocardial stiffness and reduced contractility. There is substantial evidence that the altered expression of matrix metalloproteinases (MMP) and Tenascin-C (TN-C) are associated with the progression of adverse LV remodeling. However, the role of TN-C in the development of LV hypertrophy because of chronic pressure overload as well as the regulatory role of TN-C on MMPs remains unknown. Methods and results: In a knockout mouse model of TN-C, we investigated the effect of 10 weeks of pressure overload using transverse aortic constriction (TAC). Cardiac function was determined by magnetic resonance imaging. The expression of MMP-2 and MMP-9, CD147 as well as myocardial fibrosis were assessed by immunohistochemistry. The expression of TN-C was assessed by RT-qPCR and ELISA. TN-C knockout mice showed marked reduction in fibrosis (P < 0.001) and individual cardiomyocytes size (P < 0.01), in expression of MMP-2 (P < 0.05) and MMP-9 (P < 0.001) as well as preserved cardiac function (P < 0.01) in comparison with wild-type mice after 10 weeks of TAC. In addition, CD147 expression was markedly increased under pressure overload (P < 0.01), irrespectively of genotype. TN-C significantly increased the expression of the markers of hypertrophy such as ANP and BNP as well as MMP-2 in H9c2 cells (P < 0.05, respectively). Conclusion: Our results are pointed toward a novel signaling mechanism that contributes to LV remodeling via MMPs upregulation, cardiomyocyte hypertrophy as well as myocardial fibrosis by TN-C under chronic pressure overload.
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