在aldosterone-induced高血压非诺贝特对心脏重塑的影响。

文章的细节

引用

复制到剪贴板

Lebrasseur NK, Duhaney助教,De Silva DS,崔L, Ip PC,山姆·约瑟夫·L F

在aldosterone-induced高血压非诺贝特对心脏重塑的影响。

高血压。2007年9月;(3):489 - 96。Epub 2007 7月2。

PubMed ID

17606858 (在PubMed

]

文摘

高血压和心脏重塑与心肌纤维化,左心室(LV)肥大,舒张期心衰。非诺贝特抑制aldosterone-mediated增加肌细胞基质金属蛋白酶活性和细胞外signal-regulated激酶磷酸化。还不知道过氧物酶体proliferator-activated receptor-alpha受体激动剂,非诺贝特,提高心脏重构的模型aldosterone-induced高血压和LV肥大。Twelve-week-old uninephrectomized FVB老鼠收到1%氯化钠的饮用水。Miniosmotic泵送盐水或醛固酮4周。老鼠(n = 14)未经处理或处理非诺贝特每天100毫克/公斤(n = 12) 1星期前和手术后4周。在未经处理的小鼠醛固酮增加收缩压和saline-untreated老鼠(134 + / 3和91 + / 3毫米汞柱;P < 0.01)。这是影响非诺贝特(131 + / 3毫米汞柱)。醛固酮增加LV舒张和收缩末期维度,大大减弱了非诺贝特(3.8 + / - -0.1和3.5 + / - -0.1毫米,1.5 + / - -0.1和1.15 + / - -0.1毫米,分别)。 Fenofibrate also decreased aldosterone-induced LV hypertrophy (LV weight/body weight, 4.1+/-0.2 versus 4.6+/-0.1 mg/g) and improved percent LV fractional shortening (67+/-7% versus 60+/-2%). Additionally, fenofibrate ameliorated the increased matrix metalloproteinase-2/tissue inhibitors of metalloproteinase-2 ratio and fibrosis seen in aldosterone-untreated hearts (P<0.05 for both). Furthermore, in aldosterone-untreated hearts, fenofibrate decreased transforming growth factor-beta, collagen type III (P<0.05 for both), and collagen type I (P<0.01) protein expression. Conversely fenofibrate increased peroxisome proliferator-activated receptor-alpha, peroxisome proliferator-activated receptor-gamma coactivator-1alpha expression, and acetyl coenzyme A carboxylase phosphorylation (P<0.05 for all) in aldosterone-infused hearts; uncoupling protein-3 and medium-chain acyl coenzyme A dehydrogenase protein expression decreased with fenofibrate (P<0.05 and P<0.01, respectively, versus aldosterone-infused), suggesting that improved myocardial remodeling is independent of fatty acid oxidation. Thus, fenofibrate improved aldosterone-induced LV hypertrophy independently of an effect on blood pressure with decreased fibrosis and altered extracellular matrix.

DrugBank数据引用了这篇文章

药物靶点

药物	目标	类	生物	药理作用	行动
非诺贝特	矩阵metalloproteinase-25	蛋白质	人类	未知的	抑制剂	细节
非诺贝酸	矩阵metalloproteinase-25	蛋白质	人类	未知的	未知的	细节