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J Thorac Cardiovasc Surg 2009;137:232-238
© 2009 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

Regression of pressure-induced left ventricular hypertrophy is characterized by a distinct gene expression profile

^a Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC
^b Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC
^c Carolina Cardiovascular Biology Center, University of North Carolina at Chapel Hill, Chapel Hill, NC
^d Department of Surgery, University of Utah, Salt Lake City, Utah

Received for publication January 17, 2008; revisions received July 14, 2008; accepted for publication August 7, 2008.

^_* Address for reprints: Craig H. Selzman, MD, Division of Cardiothoracic Surgery, University of Utah, Rm 3C 127 SOM, 50 North, 1900 East, Salt Lake City, UT 84132. (Email: craig.selzman{at}hsc.utah.edu).

Objective: Left ventricular hypertrophy is a highly prevalent and robust predictor of cardiovascular morbidity and mortality. Existing studies have finely detailed mechanisms involved with its development, yet clinical translation of these findings remains unsatisfactory. We propose an alternative strategy focusing on mechanisms of left ventricular hypertrophy regression rather than its progression and hypothesize that left ventricular hypertrophy regression is associated with a distinct genomic profile.

Methods: Minimally invasive transverse arch banding and debanding (or their respective sham procedures) were performed in C57Bl6 male mice. Left ventricular hypertrophy was assessed physiologically by means of transthoracic echocardiographic analysis, structurally by means of histology, and molecularly by means of real-time polymerase chain reaction. Mouse hearts were genomically analyzed with Agilent (Santa Clara, Calif) mouse 44k developmental gene chips.

Results: Compared with control animals, animals banded for 28 days had a robust hypertrophic response, as determined by means of heart weight/body weight ratio, histologic analysis, echocardiographic analysis, and fetal gene expression. These parameters were reversed within 1 week of debanding. Whole-genome arrays on left ventricular tissue revealed 288 genes differentially expressed during progression, 265 genes differentially expressed with regression, and only 23 genes shared by both processes. Signaling-related expression patterns were more prevalent with regression rather than the structure-related patterns associated with left ventricular hypertrophy progression. In addition, regressed hearts showed comparatively more changes in energy metabolism and protein production.

Conclusions: This study demonstrates an effective model for characterizing left ventricular hypertrophy and reveals that regression is genomically distinct from its development. Further examination of these expression profiles will broaden our understanding of left ventricular hypertrophy and provide a novel therapeutic paradigm focused on promoting regression of left ventricular hypertrophy and not just halting its progression.