Cardiac histone acetylation - Therapeutic opportunities abound

Timothy A. McKinsey, Eric N. Olson

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Diverse etiologic factors trigger a cardiac remodeling process in which the heart becomes abnormally enlarged with a consequent decline in cardiac function and eventual heart failure. Heart failure is traditionally treated with drugs that antagonize early signaling events at or near the cell membrane. Although such approaches have short-term efficacy, the five-year mortality rate for patients with late-stage heart failure continues to exceed 50%. Because of the redundant nature of the signaling networks that drive cardiac pathogenesis, targeting the common downstream elements of the cascades would be a more effective therapeutic strategy. Recent studies point to the importance of enzymes that control histone acetylation as stress-responsive regulators of gene expression in the heart. Given their role as nuclear integrators that couple divergent upstream signals to the gene program for cardiac remodeling, we propose that these chromatin-modifying factors represent auspicious targets for the pharmacological manipulation of cardiac disease.

Original languageEnglish (US)
Pages (from-to)206-213
Number of pages8
JournalTrends in Genetics
Volume20
Issue number4
DOIs
StatePublished - Apr 2004

Fingerprint

Acetylation
Histones
Heart Failure
Chromatin Assembly and Disassembly
Regulator Genes
Heart Diseases
Therapeutics
Cell Membrane
Pharmacology
Gene Expression
Mortality
Enzymes
Pharmaceutical Preparations
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Cardiac histone acetylation - Therapeutic opportunities abound. / McKinsey, Timothy A.; Olson, Eric N.

In: Trends in Genetics, Vol. 20, No. 4, 04.2004, p. 206-213.

Research output: Contribution to journalArticle

McKinsey, Timothy A. ; Olson, Eric N. / Cardiac histone acetylation - Therapeutic opportunities abound. In: Trends in Genetics. 2004 ; Vol. 20, No. 4. pp. 206-213.
@article{6628ee9903d3493294dca64eae59b49b,
title = "Cardiac histone acetylation - Therapeutic opportunities abound",
abstract = "Diverse etiologic factors trigger a cardiac remodeling process in which the heart becomes abnormally enlarged with a consequent decline in cardiac function and eventual heart failure. Heart failure is traditionally treated with drugs that antagonize early signaling events at or near the cell membrane. Although such approaches have short-term efficacy, the five-year mortality rate for patients with late-stage heart failure continues to exceed 50{\%}. Because of the redundant nature of the signaling networks that drive cardiac pathogenesis, targeting the common downstream elements of the cascades would be a more effective therapeutic strategy. Recent studies point to the importance of enzymes that control histone acetylation as stress-responsive regulators of gene expression in the heart. Given their role as nuclear integrators that couple divergent upstream signals to the gene program for cardiac remodeling, we propose that these chromatin-modifying factors represent auspicious targets for the pharmacological manipulation of cardiac disease.",
author = "McKinsey, {Timothy A.} and Olson, {Eric N.}",
year = "2004",
month = "4",
doi = "10.1016/j.tig.2004.02.002",
language = "English (US)",
volume = "20",
pages = "206--213",
journal = "Trends in Genetics",
issn = "0168-9525",
publisher = "Elsevier Limited",
number = "4",

}

TY - JOUR

T1 - Cardiac histone acetylation - Therapeutic opportunities abound

AU - McKinsey, Timothy A.

AU - Olson, Eric N.

PY - 2004/4

Y1 - 2004/4

N2 - Diverse etiologic factors trigger a cardiac remodeling process in which the heart becomes abnormally enlarged with a consequent decline in cardiac function and eventual heart failure. Heart failure is traditionally treated with drugs that antagonize early signaling events at or near the cell membrane. Although such approaches have short-term efficacy, the five-year mortality rate for patients with late-stage heart failure continues to exceed 50%. Because of the redundant nature of the signaling networks that drive cardiac pathogenesis, targeting the common downstream elements of the cascades would be a more effective therapeutic strategy. Recent studies point to the importance of enzymes that control histone acetylation as stress-responsive regulators of gene expression in the heart. Given their role as nuclear integrators that couple divergent upstream signals to the gene program for cardiac remodeling, we propose that these chromatin-modifying factors represent auspicious targets for the pharmacological manipulation of cardiac disease.

AB - Diverse etiologic factors trigger a cardiac remodeling process in which the heart becomes abnormally enlarged with a consequent decline in cardiac function and eventual heart failure. Heart failure is traditionally treated with drugs that antagonize early signaling events at or near the cell membrane. Although such approaches have short-term efficacy, the five-year mortality rate for patients with late-stage heart failure continues to exceed 50%. Because of the redundant nature of the signaling networks that drive cardiac pathogenesis, targeting the common downstream elements of the cascades would be a more effective therapeutic strategy. Recent studies point to the importance of enzymes that control histone acetylation as stress-responsive regulators of gene expression in the heart. Given their role as nuclear integrators that couple divergent upstream signals to the gene program for cardiac remodeling, we propose that these chromatin-modifying factors represent auspicious targets for the pharmacological manipulation of cardiac disease.

UR - http://www.scopus.com/inward/record.url?scp=1642402966&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1642402966&partnerID=8YFLogxK

U2 - 10.1016/j.tig.2004.02.002

DO - 10.1016/j.tig.2004.02.002

M3 - Article

C2 - 15041175

AN - SCOPUS:1642402966

VL - 20

SP - 206

EP - 213

JO - Trends in Genetics

JF - Trends in Genetics

SN - 0168-9525

IS - 4

ER -