Dataset Information

Constitutive Protein Kinase G Activation Exacerbates Stress-induced Cardiomyopathy

ABSTRACT: : Heart failure is associated with high morbidity and mortality, and new therapeutic targets are needed. Preclinical data suggest that pharmacological activation of protein kinase G (PKG) can reduce maladaptive ventricular remodeling and cardiac dysfunction in the stressed heart. However, clinical trial results have been mixed, and the effects of long-term PKG activation in the heart are unknown.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

SUBMITTER: Majid Ghassemian

LAB HEAD: Renate B. Pilz

PROVIDER: PXD022600 | Pride | 2023-07-20

REPOSITORIES: Pride

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Constitutive protein kinase G activation exacerbates stress-induced cardiomyopathy.

Schwaerzer Gerburg K GK Casteel Darren E DE Cividini Federico F Kalyanaraman Hema H Zhuang Shunhui S Gu Yusu Y Dalton Nancy D ND Peterson Kirk L KL Dillmann Wolfgang H WH Boss Gerry R GR Pilz Renate B RB

British journal of pharmacology 20210621 11

<h4>Background and purpose</h4>Heart failure is associated with high morbidity and mortality, and new therapeutic targets are needed. Preclinical data suggest that pharmacological activation of protein kinase G (PKG) can reduce maladaptive ventricular remodelling and cardiac dysfunction in the stressed heart. However, clinical trial results have been mixed and the effects of long-term PKG activation in the heart are unknown.<h4>Experimental approach</h4>We characterized the cardiac phenotype of ...[more]

PMID: 34000062

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Project description:In order to characterize gene expression networks linked to AT1 angiotensin receptors in the kidney, we carried out genome-wide transcriptional analysis of RNA from kidneys of wild-type (WT) and AT1A receptor-deficient mice (KOs) at baseline and after 2 days of angiotensin II infusion (1 ug/kg/min), using Affymetrix GeneChip Mouse Genome 430 2.0 Arrays. At baseline, 405 genes were differentially expressed (>1.5X) between WT and KO kidneys. Of these, more than 80% were up-regulated in the KO group including genes involved in inflammation, oxidative stress, and cell proliferation. After 2 days of angiotensin II infusion in WT mice, expression of ~805 genes was altered (18% up-regulated, 82% repressed). Genes in metabolism and ion transport pathways were up-regulated while there was attenuated expression of protective genes against oxidative stress including glutathione synthetase and mitochondrial SOD2. Angiotensin II infusion has little effect on blood pressure in KOs. Nonetheless, expression of more than 250 genes was altered in kidneys from KO mice during angiotensin II infusion; 14% were up-regulated, while 86% were repressed including genes involved in immune responses, angiogenesis, and glutathione metabolism. Between WT and KO kidneys during angiotensin II infusion, 728 genes were differentially expressed; 10% were increased and 90% were decreased in the WT group. Differentially regulated pathways included those involved in ion transport, immune responses, metabolism, apoptosis, cell proliferation, and oxidative stress. This genome-wide assessment should facilitate identification of critical distal pathways linked to blood pressure regulation. To define gene expression patterns in kidney triggered by of activation AT1 receptors, we used genome-wide transcriptional analysis of RNA from kidneys of wild-type and AT1A receptor-deficient mice at baseline and after 2 days of angiotensin II infusion (1 ug/kg/min), using Affymetrix GeneChip Mouse Genome 430 2.0 Arrays. All of the experiments were conducted with male mice 2.5 months old and included 3 mice per experimental group. Synthesis of cRNA, hybridization and scanning of chips were conducted by Duke University microarray core facility (Duke University, Durham, NC).

			Action	DRS
	FC_Mut1.raw	Raw
	FC_Mut2.raw	Raw
	FC_wt1.raw	Raw
	FC_wt2.raw	Raw
	RQ1.csv	Csv