Expression of mitochondrial regulatory genes parallels respiratory capacity and contractile function in a rat model of hypoxia-induced right ventricular hypertrophy

Zungu, Makhosazane; Young, Martin E.; Stanley, William C.; Essop, M. Faadiel

doi:10.1007/s11010-008-9867-5

Cited by 15 publications

(13 citation statements)

References 27 publications

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“…In addition, other reports demonstrated that transcripts for proteins such as fibronectin, alpha-myosin heavy chain and transforming growth factor [26], and cytochrome c oxidase and heart isoforms of uncoupling proteins [27] are asymmetrically enriched in the LV versus RV mammalian myocardium.…”

Section: Discussionmentioning

confidence: 99%

Identification of Candidate Genes Potentially Relevant to Chamber-Specific Remodeling in Postnatal Ventricular Myocardium

Torrado

Iglesias

Nespereira

et al. 2010

Journal of Biomedicine and Biotechnology

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Molecular predisposition of postnatal ventricular myocardium to chamber-dependent (concentric or eccentric) remodeling remains largely elusive. To this end, we compared gene expression in the left (LV) versus right ventricle (RV) in newborn piglets, using a differential display reverse transcription-PCR (DDRT-PCR) technique. Out of more than 5600 DDRT-PCR bands, a total of 153 bands were identified as being differentially displayed. Of these, 96 bands were enriched in the LV, whereas the remaining 57 bands were predominant in the RV. The transcripts, displaying over twofold LV-RV expression differences, were sequenced and identified by BLAST comparison to known mRNA sequences. Among the genes, whose expression was not previously recognized as being chamber-dependent, we identified a small cohort of key regulators of muscle cell growth/proliferation (MAP3K7IP2, MSTN, PHB2, APOBEC3F) and gene expression (PTPLAD1, JMJD1C, CEP290), which may be relevant to the chamber-dependent predisposition of ventricular myocardium to respond differentially to pressure (LV) and volume (RV) overloads after birth. In addition, our data demonstrate chamber-dependent alterations in expression of as yet uncharacterized novel genes, which may also be suitable candidates for association studies in animal models of LV/RV hypertrophy.

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Section: Discussionmentioning

confidence: 99%

Identification of Candidate Genes Potentially Relevant to Chamber-Specific Remodeling in Postnatal Ventricular Myocardium

Torrado

Iglesias

Nespereira

et al. 2010

Journal of Biomedicine and Biotechnology

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“…Chronic hypoxia might in some cases improve the efficiency of mitochondrial O 2 utilization (i.e. ADP/O 2 consumed) (Zungu et al, 2008) but, in general, mitochondrial function is sustained or even impaired under such conditions (Essop, 2007). The use of anaerobic metabolism in the muscle to synthesize ATP during exercise generally declines after high-altitude acclimatization, possibly because of an improved coordination between O 2 supply, glycolytic flux and cellular ATP demand (Hochachka et al, 2002).…”

Section: Tissue O 2 Utilizationmentioning

confidence: 99%

Phenotypic plasticity and genetic adaptation to high-altitude hypoxia in vertebrates

Storz

Scott

Cheviron

2010

Journal of Experimental Biology

346

343

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SummaryHigh-altitude environments provide ideal testing grounds for investigations of mechanism and process in physiological adaptation. In vertebrates, much of our understanding of the acclimatization response to high-altitude hypoxia derives from studies of animal species that are native to lowland environments. Such studies can indicate whether phenotypic plasticity will generally facilitate or impede adaptation to high altitude. Here, we review general mechanisms of physiological acclimatization and genetic adaptation to high-altitude hypoxia in birds and mammals. We evaluate whether the acclimatization response to environmental hypoxia can be regarded generally as a mechanism of adaptive phenotypic plasticity, or whether it might sometimes represent a misdirected response that acts as a hindrance to genetic adaptation. In cases in which the acclimatization response to hypoxia is maladaptive, selection will favor an attenuation of the induced phenotypic change. This can result in a form of cryptic adaptive evolution in which phenotypic similarity between high-and low-altitude populations is attributable to directional selection on genetically based trait variation that offsets environmentally induced changes. The blunted erythropoietic and pulmonary vasoconstriction responses to hypoxia in Tibetan humans and numerous high-altitude birds and mammals provide possible examples of this phenomenon. When lowland animals colonize high-altitude environments, adaptive phenotypic plasticity can mitigate the costs of selection, thereby enhancing prospects for population establishment and persistence. By contrast, maladaptive plasticity has the opposite effect. Thus, insights into the acclimatization response of lowland animals to high-altitude hypoxia can provide a basis for predicting how altitudinal range limits might shift in response to climate change.

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“…The current 20-d IHC program of brief, normobaric, moderately intense (FIO 2 9.5-10%) hypoxia bouts did not produce right ventricular hypertrophy in Wistar rats. In contrast, normobaric or hypobaric hypoxia programs in which hypoxia exposures of a similar intensity are continuous [68][69][70] or protracted (e.g. 4-8 h bouts) 71,72 provoke right ventricular hypertrophy and medial thickening of the pulmonary vasculature in this strain.…”

Section: Discussionmentioning

confidence: 85%

Normobaric, intermittent hypoxia conditioning is cardio- and vasoprotective in rats

Манухина

Belkina

Terekhina

et al. 2013

Exp Biol Med (Maywood)

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Favorable versus detrimental cardiovascular responses to intermittent hypoxia conditioning (IHC) are heavily dependent on experimental or pathological conditions, including the duration, frequency and intensity of the hypoxia exposures. Recently, we demonstrated that a program of moderate, normobaric IHC (FIO2 9.5-10% for 5-10 min/cycle, with intervening 4 min normoxia, 5-8 cycles/day for 20 days) in dogs afforded robust cardioprotection against infarction and arrhythmias induced by coronary artery occlusion-reperfusion, but this protection has not been verified in other species. Accordingly, in this investigation cardio- as well as vasoprotection were examined in male Wistar rats completing the normobaric IHC program or a sham program in which the rats continuously breathed atmospheric air. Myocardial ischemia and reperfusion (IR) was imposed by occlusion and reperfusion of the left anterior descending coronary artery in in situ experiments and by subjecting isolated, perfused hearts to global ischemia-reperfusion. Cardiac arrhythmias and myocardial infarct size were quantified in in situ experiments. Endothelial function was evaluated from the relaxation to acetylcholine of norepinephrine-precontracted aortic rings taken from in situ IR experiments, and from the increase in coronary flow produced by acetylcholine in isolated hearts. IHC sharply reduced cardiac arrhythmias during ischemia and decreased infarct size by 43% following IR. Endothelial dysfunction in aorta was marked after IR in sham rats, but not significant in IHC rats. Similar findings were found for the coronary circulations of isolated hearts. These findings support the hypothesis that moderate, normobaric IHC is cardio- and vasoprotective in a rat model of IR.

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Expression of mitochondrial regulatory genes parallels respiratory capacity and contractile function in a rat model of hypoxia-induced right ventricular hypertrophy

Cited by 15 publications

References 27 publications

Identification of Candidate Genes Potentially Relevant to Chamber-Specific Remodeling in Postnatal Ventricular Myocardium

Identification of Candidate Genes Potentially Relevant to Chamber-Specific Remodeling in Postnatal Ventricular Myocardium

Phenotypic plasticity and genetic adaptation to high-altitude hypoxia in vertebrates

Normobaric, intermittent hypoxia conditioning is cardio- and vasoprotective in rats

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