Myocardial cell death and regeneration during progression of cardiac hypertrophy to heart failure.

The Journal of Biological Chemistry
Sagartirtha SarkarSubha Sen

Abstract

Cardiac hypertrophy and ensuing heart failure are among the most common causes of mortality worldwide, yet the triggering mechanisms for progression of hypertrophy to failure are not fully understood. Tissue homeostasis depends on proper relationships between cell proliferation, differentiation, and death and any imbalance between them results in compromised cardiac function. Recently, we developed a transgenic (Tg) mouse model that overexpress myotrophin (a 12-kDa protein that stimulates myocyte growth) in heart resulting in hypertrophy that progresses to heart failure. This provided us an appropriate model to study the disease process at any point from initiation of hypertrophy end-stage heart failure. We studied detailed apoptotic signaling and regenerative pathways and found that the Tg mouse heart undergoes myocyte loss and regeneration, but only at a late stage (during transition to heart failure). Several apoptotic genes were up-regulated in 9-month-old Tg hearts compared with age-matched wild type or 4-week-old Tg hearts. Cardiac cell death during heart failure involved activation of Fas, tumor necrosis factor-alpha, and caspases 9, 8, and 3 and poly(ADP-ribose) polymerase cleavage. Tg mice with hypertrophy associated w...Continue Reading

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Citations

Jun 15, 2011·Cardiovascular Toxicology·Sathish Kumar ManeyC C Kartha
Apr 15, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Rebecca K JohnstonDhandapani Kuppuswamy
Mar 13, 2010·Journal of Cardiovascular Pharmacology·Geetha SuryakumarDhandapani Kuppuswamy
Jan 13, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Santanu RanaSagartirtha Sarkar
May 30, 2007·The Journal of Thoracic and Cardiovascular Surgery·Maria C D AbduchVera D Aiello
May 28, 2009·Anatomia, histologia, embryologia·A Contreras-RamosJ Arellano-Galindo
Nov 26, 2010·European Journal of Heart Failure·Gennaro GalassoMassimo Chiariello
Jul 12, 2005·Clinica Chimica Acta; International Journal of Clinical Chemistry·P Christian Schulze, Jürgen Kratzsch
Jul 11, 2014·Frontiers in Genetics·Ran ZhuoYihua Bei
Jun 18, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Chandan K Sen, Sashwati Roy
Dec 5, 2006·The Journal of Biological Chemistry·Roger S-Y FooMartin R Bennett
Sep 27, 2015·American Journal of Physiology. Heart and Circulatory Physiology·Rodrigo W A SouzaRobson F Carvalho
Jul 28, 2011·Journal of Cellular Physiology·Arunachal ChatterjeeSagartirtha Sarkar

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