Osteopontin gene expression in the aorta and the h

Authors: YM Liou LY Chang JM Liaw MJ Jiang

Publish Date: 2005/11/02

Volume: 12, Issue: 6, Pages: 869-880

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Abstract

It is known that there is abnormal osteopontin OPN expression at the sites of atherosclerotic lesions In the Apolipoprotein E gene knockout ApoEKO mouse a model of the atherosclerotic process altered cholesterol metabolism with associated increase in OPN expression is evident at 12–22 weeks in the aorta and at 22 weeks in the heart In this study we analyzed another animal model of hypothyroid mice created by ingestion of propylthiouracil PTU After 2 weeks of PTU ingestion the animals had significant decreases in thyroid hormones T3 and T4 and immediate increases in blood lipids/cholesterol Hypothyroid mice showed 13 15 2fold increases in blood levels of total cholesterol triglycerides and low density lipoproteincholesterol respectively Semiquantitative RTPCR analysis showed that hypothyroid mice had 14 to 2fold increases of OPN mRNA expression in the aorta and 15fold increases in the heart Hypothyroid animals treated with T3 5 μg/day for 6 days or statin 02 mg/30 g for 2 weeks reduce blood lipids and aortic OPN mRNA expression Data obtained with ELISA analyses showed 15 and 17fold increases in OPN protein in the aorta 10 weeks and the heart 22 weeks respectively This increase is close to the mRNA expression in both tissues of hypothyroid mice In addition western blots showed several variants of OPN protein expressed in the aorta and the heart The decrease in the 70 kDa OPN is accompanied by an increase in 45 kDa OPN in the aorta of hypothyroid mice In contrast only 45 kDa OPN is found in the heart of control and hypothyroid mice These data indicate that the increase of OPN mRNA and protein expression occurs in cardiovascular tissues of hypothyroid mice

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