Protein kinase C binding protein 1 inhibits hypoxia-inducible factor-1 in the heart

Schunke, Kathryn J; Walton, Chad B.; Veal, David; Mafnas, Chrisy; Anderson, Cynthia D.; Williams, Allison L; Shohet, Ralph V.

doi:10.1093/cvr/cvy278

Cited by 5 publications

(2 citation statements)

References 31 publications

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“…38,39 HIFs are transcription factors that mediate this response by decreasing global protein synthesis to conserve energy while increasing expression of stress responsive genes. 38,40 Both HIF-1α ( Hif1a ) and HIF-2α ( Epas1 ) transcripts were upregulated in untreated hearts (Table), a finding also demonstrated in other studies of animals exposed to CIH. 29 Important downstream HIFα target genes (Table denoted by asterisk and Figure S3) and transcriptional coactivators ( Crebbp , Ep300 , Ncoa1 , and Ncoa3 ; Figure S2C and Table) were also significantly upregulated in untreated compared with treated hearts, suggesting possible stabilization of HIFα in untreated animals.…”

Section: Discussionsupporting

confidence: 80%

Hypothalamic Oxytocin Neuron Activation Attenuates Intermittent Hypoxia-Induced Hypertension and Cardiac Dysfunction in an Animal Model of Sleep Apnea

et al. 2023

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Background: Obstructive sleep apnea is a prevalent and poorly treated cardiovascular disease that leads to hypertension and autonomic imbalance. Recent studies that restore cardiac parasympathetic tone using selective activation of hypothalamic OXT (oxytocin) neurons have shown beneficial cardiovascular outcomes in animal models of cardiovascular disease. This study aimed to determine if chemogenetic activation of hypothalamic OXT neurons in animals with existing obstructive sleep apnea-induced hypertension would reverse or blunt the progression of autonomic and cardiovascular dysfunction. Methods: Two groups of rats were exposed to chronic intermittent hypoxia (CIH), a model of obstructive sleep apnea, for 4 weeks to induce hypertension. During an additional 4 weeks of exposure to CIH, 1 group was treated with selective activation of hypothalamic OXT neurons while the other group was untreated. Results: Hypertensive animals exposed to CIH and treated with daily hypothalamic OXT neuron activation had lower blood pressure, faster heart rate recovery times after exercise, and improved indices of cardiac function compared with untreated hypertensive animals. Microarray analysis suggested that, compared with treated animals, untreated animals had gene expression profiles associated with cellular stress response activation, hypoxia-inducible factor stabilization, and myocardial extracellular matrix remodeling and fibrosis. Conclusions: In animals already presenting with CIH-induced hypertension, chronic activation of hypothalamic OXT neurons blunted the progression of hypertension and conferred cardioprotection after an additional 4 weeks of CIH exposure. These results have significant clinical translation for the treatment of cardiovascular disease in patients with obstructive sleep apnea.

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Section: Discussionsupporting

confidence: 80%

Hypothalamic Oxytocin Neuron Activation Attenuates Intermittent Hypoxia-Induced Hypertension and Cardiac Dysfunction in an Animal Model of Sleep Apnea

et al. 2023

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“…Although the role of ZMYND8 in the heart is unknown, mutations have been identified in genetic studies of atrioventricular septal defects and syndromic congenital cardiac abnormalities also associated with neural and hearing defects (Al Turki et al 2014; Dias et al 2022). Our lab has identified a role for ZMYND8 in suppressing the activity of hypoxia inducible factor, HIF-1, in a transgenic mouse model that expresses oxygen-stabilized HIF-1α in cardiomyocytes (Schunke et al 2019). Interestingly, acetylated ZMYND8 has both activating and repressive roles in HIF-regulated gene expression in human breast cancers (Chen et al 2018).…”

Section: Introductionmentioning

confidence: 99%

The ZMYND8 chromatin factor protects cardiomyocyte identity and function in the mouse heart

Knutson

Avelar

Shohet

2022

Preprint

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Appropriate gene expression within cardiomyocytes is coordinated by chromatin factors and is essential for heart function. We investigated the role of the chromatin reader ZMYND8 in the mouse heart using null and conditional knockouts (Zmynd8-cKO). While full-length Zmynd8 is not required for cardiomyocyte development, Zmynd8-cKO mice develop cardiomegaly, decreased cardiac function, and premature death compared to controls. Transcriptome analysis of Zmynd8-cKO cardiomyocytes reveals illegitimate expression of transcripts and proteins normally limited to skeletal muscle and integration of TNNI2 skeletal troponin into cardiac sarcomeres of mutant mice. We conclude that ZMYND8 is necessary to maintain appropriate cardiomyocyte homeostasis and gene expression.

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Mapping signalling perturbations in myocardial fibrosis via the integrative phosphoproteomic profiling of tissue from diverse sources

et al. 2020

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Protein kinase C binding protein 1 inhibits hypoxia-inducible factor-1 in the heart

Cited by 5 publications

References 31 publications

Hypothalamic Oxytocin Neuron Activation Attenuates Intermittent Hypoxia-Induced Hypertension and Cardiac Dysfunction in an Animal Model of Sleep Apnea

Hypothalamic Oxytocin Neuron Activation Attenuates Intermittent Hypoxia-Induced Hypertension and Cardiac Dysfunction in an Animal Model of Sleep Apnea

The ZMYND8 chromatin factor protects cardiomyocyte identity and function in the mouse heart

Mapping signalling perturbations in myocardial fibrosis via the integrative phosphoproteomic profiling of tissue from diverse sources

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