Evidence map›Paper›PMID 41579958›Full record

ArticleKidney international2026

Heat shock protein 70s are modifiers of endothelial function in Fabry disease.

Rakesh Verma, Audrey Cleuren, Vania Hinkovska-Galcheva, Ilka Decker, Robert Kelly, David Ginsburg, James A Shayman

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Kidney international, 2026. 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
–field-weighted citation impact
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.

  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

7 authors.

Rakesh VermaDepartment of Internal Medicine, University of Michigan Medical School, University of Michigan, Ann Arbor, Michigan, USA.
Audrey CleurenCardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Vania Hinkovska-GalchevaDepartment of Internal Medicine, University of Michigan Medical School, University of Michigan, Ann Arbor, Michigan, USA.
Ilka DeckerDepartment of Internal Medicine, University of Michigan Medical School, University of Michigan, Ann Arbor, Michigan, USA.
Robert KellyDepartment of Internal Medicine, University of Michigan Medical School, University of Michigan, Ann Arbor, Michigan, USA.
David GinsburgDepartment of Internal Medicine, University of Michigan Medical School, University of Michigan, Ann Arbor, Michigan, USA; Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA; Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA; Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.
James A ShaymanDepartment of Internal Medicine, University of Michigan Medical School, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: jshayman@umich.edu.

Funding

The Role of PAI-1 in Cerebral Microvascular Dysfunction and the Development of Alzheimer’s Disease NeuropathologyR01AG074552 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LAWRENCE, DANIEL A, MURPHY, GEOFFREY G · 2021 to 2025
$3.4M
The Molecular Genetics of HemostasisR35HL171421 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI David Ginsburg · 2024 to 2026
$2.8M
A Novel PAI-1 Function Drives Lung FibrosisR01HL163870 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Daniel A Lawrence, THOMAS H SISSON · 2023 to 2026
$2.8M
Contribution of Endothelial Changes and Increased Cardiovascular Risk to Alzheimer's Disease PathogenesisR03AG070541 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CLEUREN, AUDREY · 2021 to 2022
$350k
NHLBI NIH HHS R01 HL163870NHLBI NIH HHS R35 HL171421NIA NIH HHS R01 AG074552NIA NIH HHS R03 AG070541
6 · The paper itself

Abstract

introductionFabry disease (FD) is a systemic disorder with manifestations of heart, vascular, and kidney disease. Identical genetic variants in the α-galactosidase A (GLA) gene exhibit variable clinical phenotypes consistent with the existence of disease modifiers. Prior work in the Gla null mouse identified the vascular endothelium as a primary site for dysfunction associated with FD vasculopathy.

methodsEndothelial-specific translating ribosome affinity purification followed by RNA sequencing (EC TRAP-seq) was employed to identify differences in the in vivo endothelial cell gene expression profiles between hemizygous null male (Gla

resultsSignificant increases in transcript levels for heat shock protein (Hsp)70s (both Hsp1a and Hsp1b) and associated regulatory proteins were identified in the EC TRAP-seq analysis and verified by both Western blotting and immunohistochemistry of whole kidneys. Increased expression of Hsp70 was also confirmed in CRISPR-Cas9 mediated ablation of GLA in EA.hy926 cells (somatic hybrid used for cardiovascular disease research) and primary mouse glomerular endothelial cells. Decreased ATP-stimulated endothelial nitric oxide synthase activity was observed in GLA-deficient EA.hy926 cells, and this was worsened in the presence of two inhibitors of Hsp70 (VER155008 and PES-Cl). Additionally, increased staining for 3-nitrotyrosine was observed in the Gla knockdown cells; this was also further increased in the presence of Hsp70 inhibition. In lysosomal permeability assays, EA.hy926 GLA knockdown cells were more resistant to lysosomal permeability compared to the wild type cells. The increased resistance to lysosomal injury was reversed with HSP70 inhibition.

conclusionsEC TRAP-seq identifies Hsp70s as potential modifiers of endothelial function in FD.

Indexed as

alpha-GalactosidaseEndothelial CellsEndothelium, VascularFabry DiseaseHSP70 Heat-Shock ProteinsAnimalsDisease Models, AnimalFemaleHumansMaleMiceMice, KnockoutNitric Oxide Synthase Type IIIalpha-GalactosidaseGLA protein, humanheat-shock protein 70.1HSP70 Heat-Shock ProteinsNitric Oxide Synthase Type IIINos3 protein, mouseendothelial nitric oxide synthaseendotheliumFabry diseaseHSP70lysosomal permeability

Identifiers

PMID41579958
PMCPMC13677057

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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.