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Am J Physiol Heart Circ Physiol (January 21, 2005). doi:10.1152/ajpheart.00836.2004
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Submitted on August 18, 2004
Accepted on January 13, 2005

Regression of Pressure-Overload Induced Left Ventricular Hypertrophy in Mice

Xiao-Ming Gao1, Helen Kiriazis1, Xiao-Lei Moore1, Xin-Heng Feng1, Karen Sheppard1, Anthony Dart1, and Xiao-Jun Du1*

1 Experimental Cardiology, Baker Heart Research Institute, Melbourne, VIC, Australia; Peter MacCallum Cancer Centre, Melnourne, VIC, Australia

* To whom correspondence should be addressed. E-mail: xiaojun.du{at}baker.edu.au.

As a prelude of investigating the mechanism of regression of pressure-overload-induced left ventricular hypertrophy (LVH), we studied the time-course for the development and subsequent regression of LVH as well as accompanying alterations in cardiac function, histology and gene expression. Mice were subjected to aortic banding for 4 or 8 weeks to establish LVH and regression was then initiated by release of aortic banding for a period of 6 weeks. Progressive increase in LV mass, and gradual chamber dilatation and dysfunction occurred following aortic banding. LVH was also associated with myocyte enlargement, interstitial fibrosis, enhanced expression of atrial natriuretic peptide, collagen I, collagen III, and matrix metallopreoteinase-2, but suppressed expression of {alpha}-myosin heavy chain and sarcoplasmic reticulum Ca2+-ATPase. Aortic debanding completely or partially reversed LVH, chamber dilatation, dysfunction, myocyte size, interstitial fibrosis and gene expression pattern, each with a distinct time-course. The extent of LVH regression was dependent on the duration of pressure overload, evidenced by the fact that restoration of LV structure and function were complete in animals with 4 weeks aortic banding, but incomplete in those who had undergone 8 weeks aortic banding. In conclusion, LVH regression comprises a variety of morphological, functional and genetic components that show distinct time-courses. A longer period of pressure-overload is associated with a slower rate of LVH regression.




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