Mice Lacking Osteopontin Exhibit Increased Left Ventricular Dilation and Reduced Fibrosis After Aldosterone Infusion
Document Type
Article
Publication Date
1-1-2004
Description
Background: Osteopontin, also known as cytokine Eta-1, plays an important role in postmyocardial infarction remodeling by regulating collagen accumulation. Aldosterone promotes collagen synthesis and structural remodeling of the heart. The role of osteopontin in aldosterone-induced fibrosis and myocardial remodeling is unknown. Osteopontin expression and left ventricular structural and functional remodeling were determined in wild-type and osteopontin knockout mice after aldosterone infusion. Methods and Results: Immunohistochemical analyses showed increased interstitial osteopontin protein in the wild-type left ventricle after 7 days of aldosterone infusion. After 4 weeks of aldosterone infusion, heart rate was unchanged, and there were similar increases in blood pressure (BP) and heart-to-body weight ratio in both wild-type and knockout mice. Left ventricular end-diastolic diameter was significantly higher, whereas percent fractional shortening was significantly lower (P < .05) in knockout versus wild-type mice after 4 weeks of aldosterone infusion. Aldosterone infusion increased fibrosis and apoptosis (TUNEL-positive) in both wild-type and knockout mice. However, the increase in the extent of fibrosis and apoptosis was significantly lower in knockout hearts. Conclusions: Increased osteopontin plays an important role in the regulation of aldosterone-induced remodeling with effects on left ventricular dilation, fibrosis, and apoptosis.
Citation Information
Sam, Flora; Xie, Zhonglin; Ooi, Henry; Kerstetter, David L.; Colucci, Wilson S.; Singh, Mahipal; and Singh, Krishna. 2004. Mice Lacking Osteopontin Exhibit Increased Left Ventricular Dilation and Reduced Fibrosis After Aldosterone Infusion. American Journal of Hypertension. Vol.17(2). 188-193. https://doi.org/10.1016/j.amjhyper.2003.10.007 PMID: 14751663 ISSN: 0895-7061