压力过载
肌肉肥大
医学
内科学
心脏病学
收缩性
细胞外基质
左心室肥大
心肌梗塞
心室压
心室重构
基质金属蛋白酶
弹性蛋白
心力衰竭
血流动力学
心室肥大
内分泌学
下调和上调
血压
病理
化学
生物
细胞生物学
心肌肥大
生物化学
基因
作者
Jens Fielitz,Sebastian Philipp,Lars R. Herda,Evelyn Schuch,Bernhard Pilz,Carola Schubert,Volkmar Günzler,Roland Willenbrock,Vera Regitz‐Zagrosek
标识
DOI:10.1016/j.ejheart.2006.10.006
摘要
Abstract Background: Pressure overload leads to myocardial remodelling with collagen accumulation, left ventricular hypertrophy (LVH), neurohormonal activation and myocardial dysfunction. Prolyl 4‐hydroxylases (P4H) are involved in collagen maturation. Inhibition of P4H has been shown to prevent LV remodelling and improve survival post‐myocardial infarction. Aim: To evaluate the role of P4H in pressure overload‐induced myocardial remodelling. Methods: Male Wistar rats underwent thoracic aortic banding (AoB) and were treated with a P4H inhibitor (P4HI) or vehicle (control). Echocardiography and haemodynamic measurements were performed after 4 weeks. Collagens, matrix metalloproteinases (MMP), tissue inhibitors of MMPs (TIMP), growth factors and neurohormonal markers were quantitated in LV samples. Results: AoB led to LVH, increased LV enddiastolic pressure (LVEDP) and decreased contractility compared to sham. P4HI reversed these effects. AoB increased collagen I and III expression, which was normalized by P4HI. AoB led to deregulation of matrix remodelling enzymes, enhanced expression of growth factors and activation of the endothelin system. P4HI partially prevented deregulation of the MMP/TIMP system, inhibited upregulation of growth factors and normalized AoB‐induced ECE‐1 and ETB expression. Conclusions: P4HI leads to an improvement of AoB‐associated LV dysfunction and reduces imbalance of extracellular matrix turnover and hypertrophy‐associated gene expression. P4H inhibition could therefore be of value in treatment of myocardial remodelling accompanying pressure overload hypertrophy.
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