Evidence map›Paper›PMID 40458877›Full record

ArticleHypertension (Dallas, Tex. : 1979)2025

Degradation of nNOS in the PVN of Rats With Heart Failure: Role of CHIP.

Tapan A Patel, Kenichi Katsurada, Hong Zheng, Kaushik P Patel

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Tapan A Patel *Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha (T.A.P., K.P.P.).ORCID 0000-0002-0631-5412
Kenichi Katsurada *Division of Cardiovascular Medicine, Department of Internal Medicine (K.K.), Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan.ORCID 0000-0002-0567-1458
Hong ZhengBasic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion (H.Z.).ORCID 0000-0002-1660-3573
Kaushik P PatelDepartment of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha (T.A.P., K.P.P.).ORCID 0000-0002-4500-0819

Funding

Novel Target Mechanism (Renal Denervation) to Reduce Sodium Retention in Chronic Heart FailureR01DK114663 · NIDDK · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI PATEL, KAUSHIK P, ZHENG, HONG · 2017 to 2021
$2.1M
Novel target mechanism (renal nerves) for the beneficial actions of SGLT2 inhibition in congestive heart failureR01DK129311 · NIDDK · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI PATEL, KAUSHIK P, ZHENG, HONG · 2021 to 2024
$2.0M
NIDDK NIH HHS R01 DK114663NIDDK NIH HHS R01 DK129311
6 · The paper itself

Abstract

backgroundOne salient feature of congestive heart failure (CHF) is the exaggerated sympathetic drive. Reduced nNOS (neuronal nitric oxide synthase) within the paraventricular nucleus (PVN) is primarily responsible for the enhanced sympathetic tone in CHF. Here, we examined the role of CHIP (C-terminus of heat shock cognate protein 70-interacting protein) as a key regulator of nNOS in the PVN.

methodsCHF in rats was induced by left coronary artery ligation. Alterations in the expression of nNOS, CHIP, HSP70 (heat shock protein 70), and HSP90 (heat shock protein 90) in the PVN of CHF rats were evaluated by Western blot and immunofluorescence techniques. Neuronal NG108-15 cells were used to analyze the effect of CHIP overexpression (using the pCMV3-CHIP-GFP spark plasmid) on nNOS expression in vitro. CHIP overexpression was achieved by viral injections in the PVN of normal rats.

resultsCHIP (50%) and HSP70 (33%) were significantly upregulated in the PVN of rats with CHF. Overexpression of CHIP in neuronal NG108-15 cells showed an ≈74% increase in CHIP with a concomitant decrease in nNOS expression (≈49%). Overexpression of CHIP significantly increased ubiquitination of nNOS (46%) in NG108-15 cells. Overexpression of CHIP in the PVN of normal control rats significantly reduced NO-mediated inhibition of renal sympathetic nerve activity, blood pressure, and heart rate.

conclusionsOverall, these studies identify overexpression of CHIP, which triggers ubiquitination and proteasomal degradation of nNOS in the PVN results in reduced inhibitory sympathetic tone in CHF.

Indexed as

Heart FailureNitric Oxide Synthase Type IParaventricular Hypothalamic NucleusUbiquitin-Protein LigasesAnimalsDisease Models, AnimalHSP70 Heat-Shock ProteinsHSP90 Heat-Shock ProteinsMaleRatsRats, Sprague-DawleyHSP70 Heat-Shock ProteinsHSP90 Heat-Shock ProteinsNitric Oxide Synthase Type INos1 protein, ratStub1 protein, ratUbiquitin-Protein Ligasesheart failureheat-shock proteinsnitric oxide synthase type 1paraventricular hypothalamic nucleussympathetic nervous systemubiquitin

Identifiers

PMID40458877
PMCPMC12266964

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.