Reduction of cardiac fibrosis decreases systolic performance without affecting diastolic function in hypertensive rats
Reduction of cardiac fibrosis decreases systolic performance without affecting diastolic function in hypertensive rats
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DOI：
10.1161/01.hyp.0000125013.22494.c5
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发表时间：
2004-05-01
期刊：
影响因子：
8.3
通讯作者：
Carretero, OA
中科院分区：
文献类型：
--
作者：
Cingolani, OH;Yang, XP;Carretero, OA
压力超负荷的左心室肥厚 (LVH) 的特点是心肌细胞大小增加和纤维化。然而，尚不清楚这些成分如何影响高血压性心脏病 (HHD)。我们在两种不同的高血压大鼠模型中证明，N-乙酰基-丝氨酰-天冬氨酰-赖氨酰脯氨酸（Ac-SDKP）（一种通常存在于哺乳动物中的抗纤维化肽）可以减少心脏纤维化。为了评估抑制纤维化如何影响 HHD，用 Ac-SDKP 或媒介物治疗自发性高血压大鼠 (SHR) 和血压正常对照 (WKY)。使用体内压力-容积（PV）分析评估心脏收缩和舒张功能。还离体测定左心室被动顺应性。我们发现，在 SHR 中，Ac-SDKP 使左心室总胶原蛋白含量和间质胶原蛋白分数正常化，而不改变肌细胞直径或左心室质量。在 WKY 中，治疗后胶原蛋白没有显着变化。在 SHR 和 WKY 中体内和离体测定，Ac-SDKP 不影响左心室舒张功能，而用 Ac-SDKP 处理的 SHR 中的收缩功能显着降低，而在处理的 WKY 中则没有变化。我们的结论是，在成人 SHR 中，用 Ac-SDKP 减少左心室胶原沉积并不能改善舒张功能，反而会降低收缩功能。这些发现表明，左心室胶原蛋白总量减少本身并不一定有益于心脏功能。在 HHD 中，除了胶原蛋白数量之外的其他因素，例如肌细胞肥大和/或胶原蛋白类型或交联，可能会被用来改善心脏功能。
Pressure-overload left ventricular hypertrophy (LVH) is characterized by an increase in myocyte size and fibrosis. However, it is not clear how each of these components affects hypertensive heart disease (HHD). We have shown in 2 different rat models of hypertension that cardiac fibrosis can be reduced with N-acetyl-seryl-aspartyl-lysylproline (Ac-SDKP), an antifibrotic peptide normally present in mammals. To assess how inhibition of fibrosis affects HHD, spontaneously hypertensive rats (SHR) and normotensive controls (WKY) were treated with Ac-SDKP or vehicle. Cardiac systolic and diastolic function were assessed using in vivo pressure-volume (PV) analysis. Left ventricle passive compliance was also determined ex vivo. We found that in SHR, Ac-SDKP normalized left ventricle total collagen content and interstitial collagen fraction without changing myocyte diameter or left ventricle mass. In WKY, collagen did not change significantly after treatment. Ac-SDKP did not affect left ventricle diastolic function, determined in vivo and ex vivo in SHR and WKY, whereas systolic function was significantly decreased in SHR treated with Ac-SDKP and unchanged in treated WKY. We concluded that in adult SHR, reducing left ventricle collagen deposition with Ac-SDKP does not improve diastolic function, whereas it decreases systolic performance. These findings suggest that total left ventricle collagen reduction per se does not necessarily benefit cardiac function. In HHD, other factors besides collagen quantity, such as myocyte hypertrophy and/or collagen type or cross-link, might be targeted to improve cardiac function.