Stretch-induced hypertrophy of isolated adult rabbit cardiomyocytes
Stretch-induced hypertrophy of isolated adult rabbit cardiomyocytes
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DOI：
10.1152/ajpheart.00822.2009
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发表时间：
2010-09-01
影响因子：
4.8
通讯作者：
van der Vusse, Ger J.
中科院分区：
文献类型：
--
作者：
Blaauw, Erik;van Nieuwenhoven, Frans A.;van der Vusse, Ger J.
Blaauw E、van Nieuwenhoven FA、Willemsen P、Delhaas T、Prinzen FW、Snoeckx LH、van Bilsen M、van der Vusse GJ。拉伸诱导的离体成年兔心肌细胞肥大。 Am J Physiol Heart Circ Physiol 299：H780-H787，2010。首次发表于 2010 年 7 月 16 日； doi:10.1152/ajpheart.00822.2009.-已提出机械和体液触发因素来解释受攻击心肌细胞的肥大反应。本研究的目的是调查循环等双轴拉伸是否是离体成年兔心肌细胞肥大的直接刺激，并探讨自分泌/旁分泌因子 ANG II、转化生长因子 (TGF)-β(1) 和 IGF-I 在此过程中的潜在参与。将分离的心肌细胞暴露于 10% 循环等双轴拉伸 (1 Hz) 长达 48 小时，或用 ANG II (100 nM)、TGF-β(1) (5 ng/ml)、IGF-I (100 ng/ml)、ANG II 1 型 (AT(1)) 受体阻滞剂或拉伸成纤维细胞的条件培养基处理。循环拉伸显着增加了心肌细胞中的细胞表面积 (+3.1%)、蛋白质合成 (+21%) 和脑利钠肽 (BNP) mRNA 表达（6 倍）。 TGF-β(1) 表达在 4 小时时短暂增加 (+42%)，而心肌细胞 IGF-I 表达在所有实验条件下均未检测到。 AT(1) 受体阻滞剂坎地沙坦和厄贝沙坦 (100 nM) 不能阻止拉伸引起的肥大反应。直接暴露于 ANG II、TGF-β(1) 或 IGF-I 不会增强心肌细胞 BNP 表达。在心脏成纤维细胞中，拉伸引起 TGF-β(1) 和 IGF-I 表达显着增加约两倍。拉伸成纤维细胞的条件培养基增加了心肌细胞中的 BNP 表达（类似于 2 倍，P = 0.07）。这项研究清楚地表明，循环拉伸是诱导完全分化的兔心肌细胞肥大的强烈、直接的触发因素。目前的研究结果不支持成年兔心肌细胞拉伸介导的肥大涉及 ANG II、TGF-β(1) 或 IGF-I 的自分泌/旁分泌作用的观点。
Blaauw E, van Nieuwenhoven FA, Willemsen P, Delhaas T, Prinzen FW, Snoeckx LH, van Bilsen M, van der Vusse GJ. Stretch-induced hypertrophy of isolated adult rabbit cardiomyocytes. Am J Physiol Heart Circ Physiol 299: H780-H787, 2010. First published July 16, 2010; doi:10.1152/ajpheart.00822.2009.-Both mechanical and humoral triggers have been put forward to explain the hypertrophic response of the challenged cardiomyocyte. The aim of the present study was to investigate whether cyclic equibiaxial stretch is a direct stimulus for isolated adult rabbit cardiomyocytes to develop hypertrophy and to explore the potential involvement of the autocrine/paracrine factors ANG II, transforming growth factor (TGF)-beta(1), and IGF-I in this process. Isolated cardiomyocytes were exposed to 10% cyclic equibiaxial stretch (1 Hz) for up to 48 h or treated with ANG II (100 nM), TGF-beta(1) (5 ng/ml), IGF-I (100 ng/ml), ANG II type 1 (AT(1)) receptor blockers, or conditioned medium of stretched fibroblasts. Cyclic stretch significantly increased cell surface area (+3.1%), protein synthesis (+21%), and brain natriuretic peptide (BNP) mRNA expression (6-fold) in cardiomyocytes. TGF-beta(1) expression increased (+42%) transiently at 4 h, whereas cardiomyocyte IGF-I expression was not detectable under all experimental conditions. The AT(1) receptor blockers candesartan and irbesartan (100 nM) did not prevent the stretch-induced hypertrophic response. Direct exposure to ANG II, TGF-beta(1), or IGF-I did not enhance cardiomyocyte BNP expression. In cardiac fibroblasts, stretch elicited a significant approximately twofold increase in TGF-beta(1) and IGF-I expression. Conditioned medium of stretched fibroblasts increased BNP expression in cardiomyocytes (similar to 2-fold, P = 0.07). This study clearly indicates that cyclic stretch is a strong, direct trigger to induce hypertrophy in fully differentiated rabbit cardiomyocytes. The present findings do not support the notion that stretch-mediated hypertrophy of adult rabbit cardiomyocytes involves autocrine/paracrine actions of ANG II, TGF-beta(1), or IGF-I.