This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Webster, K. A. Articles by Bishopric, N. H. Search for Related Content PubMed PubMed Citation Articles by Webster, K. A. Articles by Bishopric, N. H. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Heart Disease in Women Heart Diseases Related Collections Apoptosis Heart failure - basic studies Hypertrophy Related Article

(Circulation. 2003;108:2954.)
© 2003 American Heart Association, Inc.

Focused Perspectives

Apoptosis Inhibitors for Heart Disease

Keith A. Webster, PhD; Nanette H. Bishopric, MD

From the Department of Molecular and Cellular Pharmacology, University of Miami Medical Center, Miami, Fla.

Correspondence to Keith A. Webster, Department of Molecular and Cellular Pharmacology, University of Miami Medical Center, 1600 NW 10th Avenue, RMSB 6038, Miami, FL 33136. E-mail kwebster@chroma.med.miami.edu

Key Words: Editorials • hypertrophy • inhibitors, caspase • heart failure

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Apoptosis may play a driving role in the transition from compensated hypertrophy to failure in the work-overloaded myocardium. In this issue of Circulation, Hayakawa et al¹ demonstrate that chronic treatment with the broad-range caspase inhibitor IDN 1965 improved cardiac function and prevented or delayed the progression to heart failure in pregnant Gq-overexpressing transgenic mice, a model of peripartum cardiomyopathy. This timely article addresses 2 important issues in cardiovascular disease: the contribution of apoptosis to development and progression of heart failure and the potential use of caspase inhibitors as therapeutic agents for this condition.

See p 3036

	Gq, Hypertrophy, and Heart Failure

 
One pathway for translating work overload and hormonal stimulation into a myocardial growth response is through activation of receptors coupled to the Gq/11 family of heterotrimeric guanine nucleotide–binding (G) proteins. Compelling evidence has been presented for a functional relationship between increased Gq activity and pathological hypertrophy, here defined as hypertrophy that progresses to decompensation. Transgenic mouse hearts expressing moderate levels of activated Gq undergo dose-dependent hypertrophy, along with activation of hypertrophy-associated marker genes.^2–4 All known upstream activators of Gq/11, including angiotensin II, norepinephrine, endothelin-1, and prostaglandin F₂, have been shown to mediate hypertrophy of cardiac myocytes in vitro and in a number of in vivo studies. Activation of Gq by these hypertrophic stimuli triggers dissociation of Gq and Gß subunits, followed by activation of phosphatidylinositol-specific phospholipase C-ß (PLC) by GTP-bound Gq. The pleiotropic response to PLC includes activation of protein kinase C, Ras, mitogen-activated protein kinases, calcineurin/nuclear . . . [Full Text of this Article]

Related Article:

Inhibition of Cardiac Myocyte Apoptosis Improves Cardiac Function and Abolishes Mortality in the Peripartum Cardiomyopathy of Gq Transgenic Mice

Yukihiro Hayakawa, Madhulika Chandra, Wenfeng Miao, Jamshid Shirani, Joan Heller Brown, Gerald W. Dorn, II, Robert C. Armstrong, and Richard N. Kitsis
Circulation 2003 108: 3036-3041. [Abstract] [Full Text]

This article has been cited by other articles:

				B. L.J.H. Kietselaer, C. P.M. Reutelingsperger, H. H. Boersma, G. A.K. Heidendal, I. H. Liem, H. J.G.M. Crijns, J. Narula, and L. Hofstra Noninvasive Detection of Programmed Cell Loss with 99mTc-Labeled Annexin A5 in Heart Failure J. Nucl. Med., April 1, 2007; 48(4): 562 - 567. [Abstract] [Full Text] [PDF]

				B. Schreiber Levocarnitine and Dialysis: A Review Nutr Clin Pract, April 1, 2005; 20(2): 218 - 243. [Abstract] [Full Text] [PDF]