Evidence map›Paper›PMID 41201771›Full record

ArticleGeroScience2026

Angiotensin II induces sex-specific ventricular remodeling in aging C57Bl/6 mice.

Ninh Khuong, Manish Mishra, Shubham Banga, Susan E Howlett

Abstract read
In one paragraph

Article in GeroScience, 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

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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

4 authors.

Ninh Khuong *Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.ORCID http://orcid.org/0000-0002-4947-3306
Manish Mishra *Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.ORCID http://orcid.org/0009-0006-3886-1553
Shubham BangaDepartment of Pharmacology, Dalhousie University, Halifax, NS, Canada.ORCID http://orcid.org/0000-0002-1730-9739
Susan E HowlettDepartment of Pharmacology, Dalhousie University, Halifax, NS, Canada. susan.howlett@dal.ca.ORCID http://orcid.org/0000-0001-5351-6308

Funding

CIHR PJT155961Heart and Stroke Foundation of Canada G-22-0031992
6 · The paper itself

Abstract

Renin-angiotensin system (RAS) activation in heart failure (HF) increases circulating angiotensin II (AII). This increases blood pressure (BP) and promotes adverse ventricular remodeling that makes HF worse. Although human HF increases with age and differs between the sexes, preclinical studies have used young, mostly male animals. We investigated sex differences in AII-induced cardiac remodeling in aging C57BL/6 mice. Mice (≈16 months) were infused with AII (3 mg/kg/day; 6 weeks; osmotic minipumps). BP (tail cuff), ventricular structure/function (echocardiography), M1 (Cd80/Mcp-1/Cd68), and M2 (Mrc1) macrophage markers and profibrotic markers (transforming growth factor beta (Tgfb1), collagen 1 (Col1a1), collagen 3 (Col3a1); qPCR/Western blot) were measured. AII treatment increased BP and heart weight/tibia length in both sexes. Interestingly, AII increased wall thickness in females but reduced it and caused left ventricular (LV) dilation in males only. AII increased E/A ratios in males and isovolumic relaxation time in both sexes, indicative of diastolic dysfunction. However, isovolumic contraction time (IVCT) increased (12.0 ± 0.7 vs. 24.3 ± 3.0 ms; p = 0.0001) and ejection fraction (EF) declined in males (68.9 ± 1.9 vs. 46.1 ± 4.5; p = 0.0001), which indicates marked systolic dysfunction. By contrast, IVCT was unaffected, and EF declined but remained well above 50% in females (68.1 ± 1.3 vs. 55.9 ± 2.0; p = 0.01). mRNA for macrophage markers (Cd80, Mrc1), Tgfb1, Col1a1, and Col3a1, plus collagen 1 protein increased in treated male ventricles. By contrast, AII increased collagen 3 protein in females compared to treated males. Thus, AII promotes inflammatory/profibrotic signaling, which contributes to fibrosis and impairs systolic function in aging males. Older females appear resistant to these effects.

Indexed as

AgingAngiotensin IIHeart FailureVentricular RemodelingAnimalsBlood PressureCollagen Type IIIDisease Models, AnimalEchocardiographyFemaleMaleMiceMice, Inbred C57BLRenin-Angiotensin SystemSex FactorsAngiotensin IICollagen Type IIIHeart failureHypertensionHypertrophyInflammationSex differences

Identifiers

PMID41201771
PMCPMC13575036

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.