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.

压力超负荷的动物模型对于了解高血压心脏病很有价值。我们描述了由肾上主动脉缩窄 (SAC) 产生的 C57BL/6J 小鼠压力超负荷诱导肥大的手术模型。与假手术对照组相比，SAC 后 1 周收缩压显着升高，左心室 (LV) 肥厚明显，由于心肌细胞肥大，左心室重量与胫骨长度之比增加了 50%。结果，左心室舒张末期壁厚度与心室半径 (h/R) 之比增加，与向心性肥厚的发展一致。左室壁增厚不足以使左室壁应力正常化，左室壁应力也会增加，导致左室收缩功能障碍，射血分数和缩短分数降低，但没有心力衰竭的证据。胎儿基因的重新表达和冠状动脉血管周围纤维化表明病理性左室重塑，心肌细胞Hif1a表达增强表明缺血。心肌细胞中干细胞因子受体 c-Kit 的表达水平较低，并且在出现强烈肥大后没有变化，表明心肌细胞 c-Kit 信号传导在压力超负荷后的病理性左室重塑中没有作用。