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.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-20000 |
| Date | 01 January 2004 |
| Creators | Sam, Flora, Xie, Zhonglin, Ooi, Henry, Kerstetter, David L., Colucci, Wilson S., Singh, Mahipal, Singh, Krishna |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Source | ETSU Faculty Works |
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