Brown Nancy J, Vaughan Douglas E, Fogo Agnes B
Deaprtment of Medicine, Vanderbilt University, Nashville, TN, USA.
J Nephrol. 2002 May-Jun;15(3):230-5.
Aldosterone modulates cardiovascular and renal injury and fibrosis in animal models. This review explores the hypothesis that aldosterone causes injury and fibrosis, in part, through effects on plasminogen activator inhibitor-1, the major physiological inhibitor of plasminogen activators in vivo. Aldosterone interacts with angiotensin II to increase plasminogen activator inhibitor-1 expression in vitro and in vivo. Plasminogen activator inhibitor-1, by inhibiting the production of plasmin from plasminogen, tips the balance in favor of extracellular matrix accumulation and promotes fibrosis. Aldosterone receptor antagonism decreases both PAI-1 expression and fibrosis in animal models. These findings have implications for the clinical management of cardiovascular and renal disease.
醛固酮可调节动物模型中的心血管和肾脏损伤及纤维化。本综述探讨了这样一种假说,即醛固酮导致损伤和纤维化,部分原因是其对纤溶酶原激活物抑制剂-1(体内纤溶酶原激活物的主要生理抑制剂)产生影响。醛固酮在体外和体内均与血管紧张素II相互作用,以增加纤溶酶原激活物抑制剂-1的表达。纤溶酶原激活物抑制剂-1通过抑制纤溶酶原产生纤溶酶,使平衡倾向于细胞外基质积聚并促进纤维化。在动物模型中,醛固酮受体拮抗作用可降低PAI-1表达和纤维化程度。这些发现对心血管和肾脏疾病的临床管理具有重要意义。