Evidence map›Paper›PMID 29389743›Full record

ArticleJournal of hypertension2018

Mice overexpressing chromogranin A display hypergranulogenic adrenal glands with attenuated ATP levels contributing to the hypertensive phenotype.

Saiful A Mir, Ying Li, Jacob D Story, Soma Bal, Linda Awdishu, Anneke A Street, Ravindra L Mehta, Prabhleen Singh, Sucheta M Vaingankar

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of hypertension, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.1field-weighted citation impact, top 56% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Saiful A MirSchool of Medicine, University of California at San Diego, La Jolla.
Ying LiSchool of Medicine, University of California at San Diego, La Jolla.
Jacob D StorySchool of Medicine, University of California at San Diego, La Jolla.
Soma BalSchool of Medicine, University of California at San Diego, La Jolla.
Linda AwdishuSchool of Medicine, University of California at San Diego, La Jolla.
Anneke A StreetSchool of Medicine, University of California at San Diego, La Jolla.
Ravindra L MehtaSchool of Medicine, University of California at San Diego, La Jolla.
Prabhleen SinghSchool of Medicine, University of California at San Diego, La Jolla.
Sucheta M VaingankarSchool of Medicine, University of California at San Diego, La Jolla.
University of California, San Diego · USVA San Diego Healthcare System · US

Funding

UAB-UCSD O'Brien Core Center for Acute Kidney Injury ResearchP30DK079337 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CURTIS, LISA M · 2008 to 2022
$18.3M
Renal Oxygenation and Mitochondrial Function in AKIR01DK107852 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SINGH, PRABHLEEN · 2016 to 2020
$1.7M
Homeostatic regulation of autonomic physiology by chromogranin AR01HL108629 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI VAINGANKAR, SUCHETA M · 2012 to 2015
$1.5M
Hypertensive kidney disease: Novel pathogenic and therapeutic pathwayR01DK094894 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI VAINGANKAR, SUCHETA M · 2012 to 2015
$1.4M
Renal Oxygenation in the Pathophysiology of Kidney DiseaseI01BX002175 · VA · VA SAN DIEGO HEALTHCARE SYSTEM · PI SINGH, PRABHLEEN · 2015 to 2025
–
BLRD VA I01 BX002175NHLBI NIH HHS R01 HL108629NIDDK NIH HHS P30 DK079337NIDDK NIH HHS R01 DK094894NIDDK NIH HHS R01 DK107852
6 · The paper itself

Abstract

objectiveElevated circulating chromogranin A (CHGA) is observed in human hypertension. CHGA is critical for granulogenesis and exocytosis of catecholamine stores from secretory large dense core vesicles (LDCV). This study aims to understand the morphological, molecular and phenotypic changes because of excess CHGA and the mechanistic link eventuating in hyper-adrenergic hypertension.

methodsBlood pressure and heart rate was monitored in mouse models expressing normal and elevated level of CHGA by telemetry. Catecholamine and oxidative stress radicals were measured. Adrenal ultrastructure, LDCV content and mitochondrial abundance were compared and respiration analyzed by Seahorse assay. Effect of CHGA dosage on adrenal ATP content, electron transport chain components and uncoupling protein 2 (UCP-2) were compared in vivo and in vitro.

resultsMice with excess-CHGA displayed hypertensive phenotype, higher heart rate and increased sympathetic tone. They had elevated plasma catecholamine and adrenal ROS levels. Excess-CHGA caused an increase in size and abundance of LDCV and adrenal mitochondria. Nonetheless, they had attenuated levels of ATP. Isolated adrenal mitochondria from mice with elevated CHGA showed higher maximal respiration rates in the presence of protonophore, which uncouples oxidative phosphorylation. Elevated CHGA resulted in overexpression of UCP2 and diminished ATP. In vitro in chromaffin cells overexpressing CHGA, concomitant increase in UCP2 protein and decreased ATP was detected.

conclusionElevated CHGA expression resulted in underlying bioenergetic dysfunction in ATP production despite higher mitochondrial mass. The outcome was unregulated negative feedback of LDCV exocytosis and secretion, resulting in elevated levels of circulating catecholamine and consequently the hypertensive phenotype.

Indexed as

Adenosine TriphosphateAdrenal GlandsAnimalsBlood PressureCatecholaminesCell RespirationCells, CulturedChromaffin CellsChromogranin AExtracellular VesiclesHeart RateHypertensionMiceMitochondriaOxidative StressPhenotypeAdenosine TriphosphateCatecholaminesChromogranin AReactive Oxygen SpeciesUcp2 protein, mouseUncoupling Protein 2

Identifiers

PMID29389743
PMCPMC6462411
OpenAlexW2789796227

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

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.