Reduction of hypoxia‐inducible heme oxygenase‐1 in the myocardium after left ventricular mechanical support

Grabellus, Florian; Schmid, Çhristof; Levkau, Bodo; Breukelmann, Dirk; Halloran, Philip F.; August, Christian; Takeda, Nobuakira; Takeda, Atsushi; Wilhelm, Markus J.; Deng, Mario C.; Baba, Hideo A.

doi:10.1002/path.1106

Cited by 32 publications

(13 citation statements)

References 27 publications

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“…The cardio protective role of fumarate has also been shown in knockout mice lacking the fumarate hydratase enyme to be mediated via up regulation of nrf-2 and the subsequent antioxidant targets [26]. The HO-1 protein has been shown to be up regulated in failing hearts and the effect reversed when these patients were supported on left ventricular assist devices [27]. …”

Section: Role Of Antioxidant Targets Of Nrf-2 In Cardiomyopathymentioning

confidence: 99%

Oxidative Stress and Cardiovascular Aging: Interaction Between NRF-2 and ADMA

Nair

Góngora

2017

CCR

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Background:The concept of antioxidant therapies assumes high importance as oxidative stress is associated with cardiovascular aging via endothelial dysfunction. This review focuses on exploring the interaction between nrf-2 and ADMA in influencing the nitric oxide pathway and cardiovascular function.Objective:A systematic review of literature from 1990 to 2016 was conducted using Pubmed and Google Scholar. The literature suggests a strong influence of nrf-2 activation on up regulation of DDAH I which degrades ADMA, the endogenous inhibitor of nitric oxide synthase. The resulting decrease of ADMA would in turn enhance nitric oxide (NO) production. This would support endothelial function by adequate NO production and homeostasis of endothelial function. Conclusion:As NO production has many positive pleiotropic effects in the cardiovascular system, such an interaction could be utilized for designing molecular therapeutics. The targets for therapy need not be limited to activation of nrf-2. Modulation of molecules downstream such as DDAH I can be used to regulate ADMA levels. Most current literature is supported by animal studies. The concept of antioxidant therapies needs to be tested in well-defined randomized control trials. The biochemical basis of nrf-2 activation needs to be substantiated in human studies.

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Section: Role Of Antioxidant Targets Of Nrf-2 In Cardiomyopathymentioning

confidence: 99%

Oxidative Stress and Cardiovascular Aging: Interaction Between NRF-2 and ADMA

Nair

Góngora

2017

CCR

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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

158

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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“…Overexpression of Hsp27 in myocytes confers protection against simulated ischemia (10). Another small molecular weight stress protein, Hsp32, has been shown to play an important role in cardiovascular adaptation to acute hypoxic stress (11). We reasoned that Hsp32 might also play a role in adaptation of infant human and rabbit heart to the stress of chronic hypoxia.…”

mentioning

confidence: 99%

Cellular Redistribution of Inducible Hsp70 Protein in the Human and Rabbit Heart in Response to the Stress of Chronic Hypoxia

Rafiee

Shi

Pritchard

et al. 2003

Journal of Biological Chemistry

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Many infants who undergo cardiac surgery have a congenital cyanotic defect where the heart is chronically perfused with hypoxemic blood. Infant hearts adapt to chronic hypoxemia by activation of intracellular protein kinase signal transduction pathways. However, the involvement of heat shock protein 70 in adaptation to chronic hypoxemia and its role in protein kinase signaling pathways is unknown. We determined expression of message and subcellular protein distribution for inducible (Hsp70i) and constitutive heat shock protein 70 (Hsc70) in chronically hypoxic and normoxic infant human and rabbit hearts and their relationship to protein kinases. In chronically hypoxic human and rabbit hearts message levels for Hsp70i were elevated 4-to 5-fold compared with normoxic hearts, Hsp70i protein was redistributed from the particulate to the cytosolic fraction. In normoxic infants Hsp70i protein was distributed almost equally between the cytosolic and particulate fractions. Hsc70 message and subcellular distribution of Hsc70 protein were unaffected by chronic hypoxia. We then determined if protein kinases influence Hsp70i protein subcellular distribution. In rabbit hearts SB203580 and chelerythrine reduced Hsp70i message levels, whereas SB203580, chelerythrine, and curcumin reversed the subcellular redistribution of Hsp70i protein caused by chronic hypoxia, with no effect in normoxic hearts, indicating regulation of Hsp70i message and subcellular distribution of Hsp70i protein in chronically hypoxic rabbit hearts is influenced by protein kinase C and mitogen-activated protein kinases, specifically p38 MAPK and JNK. We conclude the Hsp70 signal transduction pathway plays an important role in adaptation of infant human and rabbit hearts to chronic hypoxemia.

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Reduction of hypoxia‐inducible heme oxygenase‐1 in the myocardium after left ventricular mechanical support

Cited by 32 publications

References 27 publications

Oxidative Stress and Cardiovascular Aging: Interaction Between NRF-2 and ADMA

Oxidative Stress and Cardiovascular Aging: Interaction Between NRF-2 and ADMA

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

Cellular Redistribution of Inducible Hsp70 Protein in the Human and Rabbit Heart in Response to the Stress of Chronic Hypoxia

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