Hyperhomocysteinemia leads to adverse cardiac remodeling in hypertensive rats

Hyperhomocysteinemia leads to adverse cardiac remodeling in hypertensive rats
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DOI:
10.1152/ajpheart.00475.2002
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发表时间:
2002-12-01
影响因子:
4.8
通讯作者:
Kennedy, RH
Kennedy, RH
中科院分区:
医学2区
文献类型:
--
作者:
Joseph, J;Washington, A;Kennedy, RH

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高同型半胱氨酸血症(Hhe)可能是高血压心脏重构的重要因素,流行病学研究表明Hhe与心血管疾病有关。具体而言,Hhe和高血压促进的心肌和血管改变的会聚可能加剧心脏重构和心肌功能障碍。我们研究了雄性自发性高血压大鼠喂养的三种饮食之一:控制,中期HHE诱导,或严重HHE诱导。饮食干预10周后,在体外评估心脏功能,并通过组织形态计量学、免疫组化和生化技术监测心脏和冠状动脉重塑。结果表明,Hhe诱导舒张功能障碍,其特征在于舒张压-容积曲线,基线收缩功能没有显着变化。血管周围胶原水平增加Hhe,并有左心室羟脯氨酸水平的增加。肌细胞大小不受影响。冠状动脉壁厚度增加Hhe由于平滑肌增生。肥大细胞的增加与Hhe和胶原蛋白的积累平行。总之,10周的Hhe引起高血压大鼠冠状动脉重塑,心肌胶原沉积和舒张功能障碍。
Hyperhomocysteinemia (Hhe), linked to cardiovascular disease by epidemiological studies, may be an important factor in adverse cardiac remodeling in hypertension. Specifically, convergence of myocardial and vascular alterations promoted by Hhe and hypertension may exacerbate cardiac remodeling and myocardial dysfunction. We studied male spontaneously hypertensive rats fed one of three diets: control, intermediate Hhe inducing, or severe Hhe inducing. After 10 wk of dietary intervention, cardiac function was assessed in vitro, and cardiac and coronary arteriolar remodeling were monitored by histomorphometric, immunohistochemical, and biochemical techniques. Results showed that Hhe induced diastolic dysfunction, as characterized by the diastolic pressure-volume curve, without significant changes in baseline systolic function. Perivascular collagen levels were increased by Hhe, and there was an increase in left ventricular hydroxyproline levels. Myocyte size was not affected. Coronary arteriolar wall thickness increased with Hhe due to smooth muscle hyperplasia. Mast cells increased in parallel with Hhe and collagen accumulation. In summary, 10 wk of Hhe caused coronary arteriolar remodeling, myocardial collagen deposition, and diastolic dysfunction in hypertensive rats.