Evidence map›Paper›PMID 41467343›Full record

ArticleHypertension (Dallas, Tex. : 1979)2026

Inositol Requiring Enzyme 1α Mediates Hypertension and Vascular Remodeling.

Keiichi Torimoto, Yuki Nakayama, Yuka Terada, Keisuke Okuno, Stephanie Cicalese, Brooke Mangano, Tomoko Akiyama, Yayoi Kimura, Hirotoshi Utsunomiya, Tomoki Hashimoto and 3 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Keiichi Torimoto *Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (K.T., K.O., S.C., S.E.).ORCID 0000-0002-5174-5980
Yuki Nakayama *Department of Surgery (Y.N., Y.T., S.E.), the Hypertension and Kidney Center, and the Heart Institute, Morsani College of Medicine, University of South Florida, Tampa.
Yuka TeradaDepartment of Surgery (Y.N., Y.T., S.E.), the Hypertension and Kidney Center, and the Heart Institute, Morsani College of Medicine, University of South Florida, Tampa.
Keisuke OkunoCardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (K.T., K.O., S.C., S.E.).ORCID 0000-0002-9466-0530
Stephanie CicaleseCardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (K.T., K.O., S.C., S.E.).ORCID 0000-0003-1688-5053
Brooke ManganoDepartment of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH (B.M., P.O.-O.).
Tomoko AkiyamaAdvanced Medical Research Center, Yokohama City University, Japan (T.A., Y.K.).ORCID 0009-0002-9050-962X
Yayoi KimuraAdvanced Medical Research Center, Yokohama City University, Japan (T.A., Y.K.).ORCID 0000-0002-4612-4602
Hirotoshi UtsunomiyaDepartment of Rehabilitation, Osaka Kawasaki Rehabilitation University, Kaizuka, Japan (H.U.).
Tomoki HashimotoDepartments of Neurosurgery and Neurobiology, Barrow Aneurysm and AVM Research Center, Barrow Neurological Institute, Phoenix, AZ (T.H.).ORCID 0000-0002-6046-9148
Jin O-UchiDepartment of Molecular Pharmacology and Physiology (J.O.-U.), the Hypertension and Kidney Center, and the Heart Institute, Morsani College of Medicine, University of South Florida, Tampa.ORCID 0000-0001-7566-5400
Patrick Osei-OwusuDepartment of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH (B.M., P.O.-O.).ORCID 0000-0002-4581-7044
Satoru EguchiDepartment of Surgery (Y.N., Y.T., S.E.), the Hypertension and Kidney Center, and the Heart Institute, Morsani College of Medicine, University of South Florida, Tampa.ORCID 0000-0002-8407-7501

Funding

Roles of aging and cellular senescence in the development of intracranial aneurysm ruptureR01AG077780 · NIA · ST. JOSEPH'S HOSPITAL AND MEDICAL CENTER · PI SATORU EGUCHI, TOMOKI HASHIMOTO · 2023 to 2026
$2.4M
Vascular Pyruvate Kinase M2 in HypertensionR01HL174004 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI SATORU EGUCHI, Patrick Osei-Owusu · 2025 to 2026
$1.4M
NHLBI NIH HHS R01 HL174004NIA NIH HHS R01 AG077780
6 · The paper itself

Abstract

backgroundChronic unfolded protein response due to endoplasmic reticulum stress has been proposed as a therapeutic target for hypertension. Here, we tested our hypothesis that inactivation of one of the central unfolded protein response effectors, inositol-requiring enzyme 1α, mitigates hypertension and vascular remodeling in mice infused with angiotensin II.

methodsC57BL6 mice were infused with angiotensin II for 2 weeks with or without an inositol-requiring enzyme 1α inhibitor KIRA6 treatment to evaluate blood pressure and cardiovascular remodeling. Mouse small mesenteric arteries were used to assess vascular reactivity. Rat vascular smooth muscle cells were used to assess inositol-requiring enzyme 1α activation, intracellular Ca

resultsKIRA6 treatment mitigated hypertension induced by angiotensin II infusion. KIRA6 treatment also prevented angiotensin II-induced vascular thickening and perivascular fibrosis. Immunohistochemical staining of aortas indicated that phosphorylated inositol-requiring enzyme 1α signal in vascular smooth muscle cells was elevated with angiotensin II infusion and attenuated with KIRA6 treatment. Vasoconstriction in small mesenteric arteries after incubation with angiotensin II was attenuated by KIRA6 coincubation. Angiotensin II-induced elevation in intracellular Ca

conclusionsTargeting inositol-requiring enzyme 1α is a potential therapy for hypertension and vascular remodeling by reducing vascular resistance, mitigating intracellular Ca

Indexed as

HypertensionMuscle, Smooth, VascularVascular RemodelingAngiotensin IIAnimalsBlood PressureDisease Models, AnimalMaleMesenteric ArteriesMiceMice, Inbred C57BLMyocytes, Smooth MuscleRatsVasoconstrictionAngiotensin IIaortablood pressurefibrosishypertensioninositol

Identifiers

PMID41467343
PMCPMC12755729

What Socratic holds

Textmetadata
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 Socratic graph.