Division of Molecular Cardiology and Biophysics, Victor Chang Cardiac Research Institute, 405 Liverpool Street, Darlinghurst, Sydney, NSW, 2010, Australia.
St Vincent's Clinical School, University of New South Wales, Sydney, NSW, 2052, Australia.
Sci Rep. 2020 Sep 18;10(1):15318. doi: 10.1038/s41598-020-72273-3.
Animal models of pressure overload are valuable for understanding hypertensive heart disease. We characterised a surgical model of pressure overload-induced hypertrophy in C57BL/6J mice produced by suprarenal aortic constriction (SAC). Compared to sham controls, at one week post-SAC systolic blood pressure was significantly elevated and left ventricular (LV) hypertrophy was evident by a 50% increase in the LV weight-to-tibia length ratio due to cardiomyocyte hypertrophy. As a result, LV end-diastolic wall thickness-to-chamber radius (h/R) ratio increased, consistent with the development of concentric hypertrophy. LV wall thickening was not sufficient to normalise LV wall stress, which also increased, resulting in LV systolic dysfunction with reductions in ejection fraction and fractional shortening, but no evidence of heart failure. Pathological LV remodelling was evident by the re-expression of fetal genes and coronary artery perivascular fibrosis, with ischaemia indicated by enhanced cardiomyocyte Hif1a expression. The expression of stem cell factor receptor, c-Kit, was low basally in cardiomyocytes and did not change following the development of robust hypertrophy, suggesting there is no role for cardiomyocyte c-Kit signalling in pathological LV remodelling following pressure overload.
动物压力超负荷模型对于理解高血压性心脏病非常有价值。我们对 C57BL/6J 小鼠通过肾上主动脉缩窄（SAC）产生的压力超负荷诱导肥大的手术模型进行了特征描述。与假手术对照组相比，SAC 后一周，收缩压显著升高，左心室（LV）重量与胫骨长度比值增加 50%，表明心肌细胞肥大导致 LV 肥大。结果，LV 舒张末期壁厚度与腔半径（h/R）比值增加，与向心性肥厚的发展一致。LV 壁增厚不足以使 LV 壁应力正常化，LV 壁应力也增加，导致 LV 收缩功能障碍，射血分数和缩短分数降低，但没有心力衰竭的证据。LV 病理性重塑表现为胎儿基因的重新表达和冠状动脉血管周围纤维化，缺血表现为心肌细胞 Hif1a 表达增强。干细胞因子受体 c-Kit 的表达在心肌细胞中基础较低，在形成强大的肥大后并未改变，这表明在压力超负荷后，心肌细胞 c-Kit 信号传导在病理性 LV 重塑中没有作用。
