Cardioprotective and antiapoptotic effects of heme oxygenase-1 in the failing heart

Guangwu Wang, Tariq Hamid, Rachel J. Keith, Guihua Zhou, Charles R. Partridge, Xilin Xiang, Justin R. Kingery, Robert K. Lewis, Qianhong Li, D. Gregg Rokosh, Rachael Ford, Francis G. Spinale, Daniel W. Riggs, Sanjay Srivastava, Aruni Bhatnagar, Roberto Bolli, Sumanth D. Prabhu

Research output: Contribution to journalArticle

Abstract

BACKGROUND-: Heme oxygenase-1 (HO-1) is an inducible stress-response protein that imparts antioxidant and antiapoptotic effects. However, its pathophysiological role in cardiac remodeling and chronic heart failure (HF) is unknown. We hypothesized that induction of HO-1 in HF alleviates pathological remodeling. METHODS AND RESULTS-: Adult male nontransgenic and myocyte-restricted HO-1 transgenic mice underwent either sham operation or coronary ligation to induce HF. Four weeks after ligation, nontransgenic HF mice exhibited postinfarction left ventricular (LV) remodeling and dysfunction, hypertrophy, fibrosis, oxidative stress, apoptosis, and reduced capillary density, associated with a 2-fold increase in HO-1 expression in noninfarcted myocardium. Compared with nontransgenic mice, HO-1 transgenic HF mice exhibited significantly (P2O2-induced cardiomyocyte apoptosis and cell death. Finally, in vivo treatment with CORM-3 alleviated postinfarction LV remodeling, p53 expression, and apoptosis. CONCLUSIONS-: HO-1 induction in the failing heart is an important cardioprotective adaptation that opposes pathological LV remodeling, and this effect is mediated, at least in part, by CO-dependent inhibition of mitochondrial permeability transition and apoptosis. Augmentation of HO-1 or its product, CO, may represent a novel therapeutic strategy for ameliorating HF.

Original languageEnglish (US)
Pages (from-to)1912-1925
Number of pages14
JournalCirculation
Volume121
Issue number17
DOIs
StatePublished - May 2010
Externally publishedYes

Fingerprint

Heme Oxygenase-1
Heart Failure
Ventricular Remodeling
Apoptosis
Carbon Monoxide
Ligation
Left Ventricular Dysfunction
Heat-Shock Proteins
Cardiac Myocytes
Muscle Cells
Hypertrophy
Transgenic Mice
Permeability
Myocardium
Oxidative Stress
Fibrosis
Cell Death
Antioxidants

Keywords

  • Apoptosis
  • Carbon monoxide
  • Cardiac remodeling
  • Heart failure
  • Heme oxygenase-1
  • Ventricular

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Wang, G., Hamid, T., Keith, R. J., Zhou, G., Partridge, C. R., Xiang, X., ... Prabhu, S. D. (2010). Cardioprotective and antiapoptotic effects of heme oxygenase-1 in the failing heart. Circulation, 121(17), 1912-1925. https://doi.org/10.1161/CIRCULATIONAHA.109.905471

Cardioprotective and antiapoptotic effects of heme oxygenase-1 in the failing heart. / Wang, Guangwu; Hamid, Tariq; Keith, Rachel J.; Zhou, Guihua; Partridge, Charles R.; Xiang, Xilin; Kingery, Justin R.; Lewis, Robert K.; Li, Qianhong; Rokosh, D. Gregg; Ford, Rachael; Spinale, Francis G.; Riggs, Daniel W.; Srivastava, Sanjay; Bhatnagar, Aruni; Bolli, Roberto; Prabhu, Sumanth D.

In: Circulation, Vol. 121, No. 17, 05.2010, p. 1912-1925.

Research output: Contribution to journalArticle

Wang, G, Hamid, T, Keith, RJ, Zhou, G, Partridge, CR, Xiang, X, Kingery, JR, Lewis, RK, Li, Q, Rokosh, DG, Ford, R, Spinale, FG, Riggs, DW, Srivastava, S, Bhatnagar, A, Bolli, R & Prabhu, SD 2010, 'Cardioprotective and antiapoptotic effects of heme oxygenase-1 in the failing heart', Circulation, vol. 121, no. 17, pp. 1912-1925. https://doi.org/10.1161/CIRCULATIONAHA.109.905471
Wang G, Hamid T, Keith RJ, Zhou G, Partridge CR, Xiang X et al. Cardioprotective and antiapoptotic effects of heme oxygenase-1 in the failing heart. Circulation. 2010 May;121(17):1912-1925. https://doi.org/10.1161/CIRCULATIONAHA.109.905471
Wang, Guangwu ; Hamid, Tariq ; Keith, Rachel J. ; Zhou, Guihua ; Partridge, Charles R. ; Xiang, Xilin ; Kingery, Justin R. ; Lewis, Robert K. ; Li, Qianhong ; Rokosh, D. Gregg ; Ford, Rachael ; Spinale, Francis G. ; Riggs, Daniel W. ; Srivastava, Sanjay ; Bhatnagar, Aruni ; Bolli, Roberto ; Prabhu, Sumanth D. / Cardioprotective and antiapoptotic effects of heme oxygenase-1 in the failing heart. In: Circulation. 2010 ; Vol. 121, No. 17. pp. 1912-1925.
@article{617b2bb2f1164b298b8b5a6b3702b21c,
title = "Cardioprotective and antiapoptotic effects of heme oxygenase-1 in the failing heart",
abstract = "BACKGROUND-: Heme oxygenase-1 (HO-1) is an inducible stress-response protein that imparts antioxidant and antiapoptotic effects. However, its pathophysiological role in cardiac remodeling and chronic heart failure (HF) is unknown. We hypothesized that induction of HO-1 in HF alleviates pathological remodeling. METHODS AND RESULTS-: Adult male nontransgenic and myocyte-restricted HO-1 transgenic mice underwent either sham operation or coronary ligation to induce HF. Four weeks after ligation, nontransgenic HF mice exhibited postinfarction left ventricular (LV) remodeling and dysfunction, hypertrophy, fibrosis, oxidative stress, apoptosis, and reduced capillary density, associated with a 2-fold increase in HO-1 expression in noninfarcted myocardium. Compared with nontransgenic mice, HO-1 transgenic HF mice exhibited significantly (P2O2-induced cardiomyocyte apoptosis and cell death. Finally, in vivo treatment with CORM-3 alleviated postinfarction LV remodeling, p53 expression, and apoptosis. CONCLUSIONS-: HO-1 induction in the failing heart is an important cardioprotective adaptation that opposes pathological LV remodeling, and this effect is mediated, at least in part, by CO-dependent inhibition of mitochondrial permeability transition and apoptosis. Augmentation of HO-1 or its product, CO, may represent a novel therapeutic strategy for ameliorating HF.",
keywords = "Apoptosis, Carbon monoxide, Cardiac remodeling, Heart failure, Heme oxygenase-1, Ventricular",
author = "Guangwu Wang and Tariq Hamid and Keith, {Rachel J.} and Guihua Zhou and Partridge, {Charles R.} and Xilin Xiang and Kingery, {Justin R.} and Lewis, {Robert K.} and Qianhong Li and Rokosh, {D. Gregg} and Rachael Ford and Spinale, {Francis G.} and Riggs, {Daniel W.} and Sanjay Srivastava and Aruni Bhatnagar and Roberto Bolli and Prabhu, {Sumanth D.}",
year = "2010",
month = "5",
doi = "10.1161/CIRCULATIONAHA.109.905471",
language = "English (US)",
volume = "121",
pages = "1912--1925",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "17",

}

TY - JOUR

T1 - Cardioprotective and antiapoptotic effects of heme oxygenase-1 in the failing heart

AU - Wang, Guangwu

AU - Hamid, Tariq

AU - Keith, Rachel J.

AU - Zhou, Guihua

AU - Partridge, Charles R.

AU - Xiang, Xilin

AU - Kingery, Justin R.

AU - Lewis, Robert K.

AU - Li, Qianhong

AU - Rokosh, D. Gregg

AU - Ford, Rachael

AU - Spinale, Francis G.

AU - Riggs, Daniel W.

AU - Srivastava, Sanjay

AU - Bhatnagar, Aruni

AU - Bolli, Roberto

AU - Prabhu, Sumanth D.

PY - 2010/5

Y1 - 2010/5

N2 - BACKGROUND-: Heme oxygenase-1 (HO-1) is an inducible stress-response protein that imparts antioxidant and antiapoptotic effects. However, its pathophysiological role in cardiac remodeling and chronic heart failure (HF) is unknown. We hypothesized that induction of HO-1 in HF alleviates pathological remodeling. METHODS AND RESULTS-: Adult male nontransgenic and myocyte-restricted HO-1 transgenic mice underwent either sham operation or coronary ligation to induce HF. Four weeks after ligation, nontransgenic HF mice exhibited postinfarction left ventricular (LV) remodeling and dysfunction, hypertrophy, fibrosis, oxidative stress, apoptosis, and reduced capillary density, associated with a 2-fold increase in HO-1 expression in noninfarcted myocardium. Compared with nontransgenic mice, HO-1 transgenic HF mice exhibited significantly (P2O2-induced cardiomyocyte apoptosis and cell death. Finally, in vivo treatment with CORM-3 alleviated postinfarction LV remodeling, p53 expression, and apoptosis. CONCLUSIONS-: HO-1 induction in the failing heart is an important cardioprotective adaptation that opposes pathological LV remodeling, and this effect is mediated, at least in part, by CO-dependent inhibition of mitochondrial permeability transition and apoptosis. Augmentation of HO-1 or its product, CO, may represent a novel therapeutic strategy for ameliorating HF.

AB - BACKGROUND-: Heme oxygenase-1 (HO-1) is an inducible stress-response protein that imparts antioxidant and antiapoptotic effects. However, its pathophysiological role in cardiac remodeling and chronic heart failure (HF) is unknown. We hypothesized that induction of HO-1 in HF alleviates pathological remodeling. METHODS AND RESULTS-: Adult male nontransgenic and myocyte-restricted HO-1 transgenic mice underwent either sham operation or coronary ligation to induce HF. Four weeks after ligation, nontransgenic HF mice exhibited postinfarction left ventricular (LV) remodeling and dysfunction, hypertrophy, fibrosis, oxidative stress, apoptosis, and reduced capillary density, associated with a 2-fold increase in HO-1 expression in noninfarcted myocardium. Compared with nontransgenic mice, HO-1 transgenic HF mice exhibited significantly (P2O2-induced cardiomyocyte apoptosis and cell death. Finally, in vivo treatment with CORM-3 alleviated postinfarction LV remodeling, p53 expression, and apoptosis. CONCLUSIONS-: HO-1 induction in the failing heart is an important cardioprotective adaptation that opposes pathological LV remodeling, and this effect is mediated, at least in part, by CO-dependent inhibition of mitochondrial permeability transition and apoptosis. Augmentation of HO-1 or its product, CO, may represent a novel therapeutic strategy for ameliorating HF.

KW - Apoptosis

KW - Carbon monoxide

KW - Cardiac remodeling

KW - Heart failure

KW - Heme oxygenase-1

KW - Ventricular

UR - http://www.scopus.com/inward/record.url?scp=77951878150&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951878150&partnerID=8YFLogxK

U2 - 10.1161/CIRCULATIONAHA.109.905471

DO - 10.1161/CIRCULATIONAHA.109.905471

M3 - Article

C2 - 20404253

AN - SCOPUS:77951878150

VL - 121

SP - 1912

EP - 1925

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 17

ER -