Regression of pressure overload-induced left ventricular hypertrophy in mice

1 Experimental Cardiology Laboratory, Baker Heart Research Institute, and Alfred Heart Centre, Alfred Hospital, and 2 Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia Submitted 18 August 2004 ; accepted in final form 13 January 2005 As a prelude to investigating the mechanism of regression of pressure overload-induced left ventricular (LV) 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 wk to establish LVH, and regression was initiated by release of aortic banding for 6 wk. Progressive increase in LV mass and gradual chamber dilatation and dysfunction occurred after aortic banding. LVH was also associated with myocyte enlargement, interstitial fibrosis, and enhanced expression of atrial natriuretic peptide, collagen I, collagen III, and matrix metalloproteinase-2 but suppressed expression of -myosin heavy chain and sarcoplasmic reticulum Ca 2+ -ATPase. Aortic debanding completely or partially reversed LVH, chamber dilatation and 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 was complete in animals subjected to 4 wk of aortic banding but incomplete in animals subjected to 8 wk of 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. aortic banding; cardiac function/remodeling; model Address for reprint requests and other correspondence: X.-J. Du, Baker Heart Research Institute, PO Box 6492, St. Kilda Rd. Central, Melbourne, Victoria 8008, Australia (E-mail: xiaojun.du{at}baker.edu.au )