Chamber-specific Regulation of Heme Oxygenase-1 (Heat Shock Protein 32) in Right-sided Congestive Heart Failure

Raju, V.S.; Imai, N.; Liang, Chang‐seng

doi:10.1006/jmcc.1999.0995

Cited by 44 publications

(31 citation statements)

References 33 publications

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“…The present study also failed to observe a relation between the extent of myocardial fibrosis and NOS3 gene expression or HO-1 gene expression, which is upregulated in the failing myocardium and could augment the bioavailability of NO by protection against oxidative stress (28). The lack of relations between myocardial fibrosis and NOS3 or antioxidative enzymes such as HO-1 does not exclude the involvement of NOS3 or antioxidative enzymes in the development of myocardial fibrosis but suggests excessive myocardial fibrosis in DCM to result more from upregulation of stimulatory pathways such as angiotensin II, endothelin, and aldosterone than from downregulation of inhibitory pathways (36).…”

Section: No Fibrosis and LV Preload Reservecontrasting

confidence: 96%

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Myocardial fibrosis blunts nitric oxide synthase-related preload reserve in human dilated cardiomyopathy

Bronzwaer

Heymes

Visser

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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. Myocardial fibrosis blunts nitric oxide synthase-related preload reserve in human dilated cardiomyopathy. Am J Physiol Heart Circ Physiol 284: H10-H16, 2003; 10.1152/ajpheart.00401.2002.-The purpose of the study was to investigate interactions between myocardial nitric oxide synthase (NOS) and myocardial fibrosis, both of which determine left ventricular (LV) preload reserve in patients with nonischemic dilated cardiomyopathy (DCM). In previous animal experiments, chronic inhibition of NOS induced myocardial fibrosis and limited LV preload reserve. Twenty-eight DCM patients underwent LV catheterization, balloon caval occlusions (BCO; n ϭ 8), intracoronary substance P infusion (n ϭ 8), and procurement of LV endomyocardial biopsies for determinations of collagen volume fraction (CVF), of gene expression of NOS2, NOS3, heme oxygenase (HO)-1, and TNF-␣, and of NOS2 protein. CVF was unrelated to the intensity of NOS2, NOS3, HO-1, or TNF-␣ gene expression or of NOS2 protein expression. Preload recruitable LV stroke work (PR-LVSW) correlated directly with NOS2 gene expression (P ϭ 0.001) and inversely with CVF (P ϭ 0.04). High CVF (Ͼ10%) reduced baseline LVSW and PR-LVSW at each level of NOS2 gene expression. In DCM, myocardial fibrosis is unrelated to the intensity of myocardial gene expression of NOS, antioxidative enzymes (HO-1), or cytokines (TNF-␣) and blunts NOS2-related recruitment of LV preload reserve. collagen; diastole; myocardial contraction HIGHER LEFT VENTRICULAR (LV) endomyocardial nitric oxide (NO) synthase (NOS) gene expression enables patients with dilated cardiomyopathy (DCM) to recruit LV preload reserve as evident from their higher LV stroke work (LVSW) at elevated LV filling pressures (13). This ability to recruit LV preload reserve could result from an acute direct myocardial action of NO, because intracoronary infusion of substance P, which releases NO from the coronary endothelium, induces an instantaneous increase in LVSW in DCM patients with elevated LV filling pressures (13). This increase in LVSW is accompanied by a rightward shift of the diastolic LV pressure-volume relation. A similar NOrelated rightward shift of the diastolic LV pressurevolume relation was previously observed in control and aortic stenosis patients after intracoronary infusion of a NO donor (20,24) and in DCM patients after intracoronary infusion of enalaprilat (37). Acute effects of NO on myocardial diastolic distensibility have also been reported in experimental preparations. In isolated rat cardiomyocytes, exposure to cGMP, the second messenger of NO, increases diastolic cell length (32), and, in isolated guinea pig hearts, a coronary perfusate containing a specific NOS inhibitor results in an acute reduction of LV stroke volume because of a leftward shift of the diastolic LV pressure-volume relation (27).The ability of NO to preserve LV diastolic distensibility could result not only from its acute direct myocardial actions but also from chronic effects on LV hypertrophy and on collagen turnover within the cardiac i...

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Section: No Fibrosis and LV Preload Reservecontrasting

confidence: 96%

“…In eight patients (Table 1, patients [21][22][23][24][25][26][27][28], a 5-min intracoronary infusion of substance P (20 pmol/min) was performed (13). Substance P causes receptor-mediated coronary endothelial release of NO.…”

Section: Methodsmentioning

confidence: 99%

Myocardial fibrosis blunts nitric oxide synthase-related preload reserve in human dilated cardiomyopathy

Bronzwaer

Heymes

Visser

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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“…Prior studies have reported that HO-1 is upregulated in human failing hearts [84] and in animal models of right ventricular failure [85]. The HO-1 expression in the noninfarct myocardium was increased four weeks after coronary ligation, and cardiomyocyte-specific HO-1 transgenic mice showed improved postinfarction survival and attenuated cardiac hypertrophy, interstitial fibrosis, oxidative stress, and apoptosis [86, 87].…”

Section: Role Of the Nrf2 Pathway In Ischemia-induced Cardiac Remomentioning

confidence: 99%

The Role of Nrf2-Mediated Pathway in Cardiac Remodeling and Heart Failure

Zhou

Sun

Zhang

et al. 2014

Oxidative Medicine and Cellular Longevity

162

138

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Heart failure (HF) is frequently the consequence of sustained, abnormal neurohormonal, and mechanical stress and remains a leading cause of death worldwide. The key pathophysiological process leading to HF is cardiac remodeling, a term referring to maladaptation to cardiac stress at the molecular, cellular, tissue, and organ levels. HF and many of the conditions that predispose one to HF are associated with oxidative stress. Increased generation of reactive oxygen species (ROS) in the heart can directly lead to increased necrosis and apoptosis of cardiomyocytes which subsequently induce cardiac remodeling and dysfunction. Nuclear factor-erythroid-2- (NF-E2-) related factor 2 (Nrf2) is a transcription factor that controls the basal and inducible expression of a battery of antioxidant genes and other cytoprotective phase II detoxifying enzymes that are ubiquitously expressed in the cardiovascular system. Emerging evidence has revealed that Nrf2 and its target genes are critical regulators of cardiovascular homeostasis via the suppression of oxidative stress, which is the key player in the development and progression of HF. The purpose of this review is to summarize evidence that activation of Nrf2 enhances endogenous antioxidant defenses and counteracts oxidative stress-associated cardiac remodeling and HF.

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“…, inflammatory cytokines, catecholamines) that, while initially compensatory and protective, ultimately produce long-term detrimental effects. Although prior studies have reported that HO-1 is upregulated in human failing hearts [15] and in animal models of right ventricular failure [16], it is not clear whether such long-term induction is beneficial or detrimental. Accordingly, in this study we tested the hypothesis that HO-1 upregulation in the failing heart is a cardioprotective adaptation that ameliorates pathological LV remodeling.…”

Section: Introductionmentioning

confidence: 99%

Cardioprotective and Antiapoptotic Effects of Heme Oxygenase-1 in the Failing Heart

et al. 2010

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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 (PϽ0.05) improved postinfarction survival (94% versus 57%) and less LV dilatation (end-diastolic volume, 46Ϯ8 versus 85Ϯ32 L), mechanical dysfunction (ejection fraction, 65Ϯ9% versus 49Ϯ16%), hypertrophy (LV/tibia length 4.4Ϯ0.4 versus 5.2Ϯ0.6 mg/mm), interstitial fibrosis (11.2Ϯ3.1% versus 18.5Ϯ3.5%), and oxidative stress (3-fold reduction in tissue malondialdehyde). Moreover, myocyte-specific HO-1 overexpression in HF promoted tissue neovascularization and ameliorated myocardial p53 expression (2-fold reduction) and apoptosis. In isolated mitochondria, mitochondrial permeability transition was inhibited by HO-1 in a carbon monoxide (CO)-dependent manner and was recapitulated by the CO donor tricarbonylchloro(glycinato)ruthenium(II) (CORM-3). HO-1-derived CO also prevented H 2 O 2 -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.

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Chamber-specific Regulation of Heme Oxygenase-1 (Heat Shock Protein 32) in Right-sided Congestive Heart Failure

Cited by 44 publications

References 33 publications

Myocardial fibrosis blunts nitric oxide synthase-related preload reserve in human dilated cardiomyopathy

Myocardial fibrosis blunts nitric oxide synthase-related preload reserve in human dilated cardiomyopathy

The Role of Nrf2-Mediated Pathway in Cardiac Remodeling and Heart Failure

Cardioprotective and Antiapoptotic Effects of Heme Oxygenase-1 in the Failing Heart

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