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← All articlesEditorial brief · abstract-levelScore 71/100Confidence medium
biorxiv2026-09-03cardiologymetabolismlipid

Sex and NOS dose split older mice into HFpEF-like females and HFrEF-like males under fat plus L-NAME

Older mice on high-fat diet plus NOS inhibition do not make one heart-failure model. Low-dose L-NAME females get diastolic failure with preserved systole. High-dose males get hypertension and systolic failure. Lipidomes share sphingolipid and phospholipid remodels with sex-specific phosphatidylinositol and lysophosphatidylcholine species. Transcriptomes share matrix, calcium-handling, and metabolic paths.

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Signal profile (abstract-level)

cardiology · metabolism · lipid

Score 71/100BIORXIVmedium confidencecardiology
71
Importance
50
Mito signal
67
Dysfunction
75
Evidence
65
Translational

Editorial signal profile from the abstract (importance score, mito keywords, dysfunction tags, evidence density, translational cues). Not a figure reproduced from the preprint PDF.

Finding. The high-fat plus L-NAME mouse is not one heart-failure. Sun, Young, McMullen and colleagues show older females on low-dose NOS inhibition get a HFpEF-like heart: stiff diastole, poor exercise, systole intact. Turn the dose up and females add inflammatory transcription without more diastolic wreckage. Males on high dose become hypertensive and systolic-failed, a HFrEF-like picture. Blood lipids remodel sphingolipids and phospholipids in both sexes, with sex-specific phosphatidylinositol and lysophosphatidylcholine. Heart RNA shares matrix, calcium-handling, and metabolic paths.

Score 71. Sex-dose split of a workhorse model. Mitochondria inferred. Confidence is medium.

What to do with it Do not cite a single L-NAME+HFD paper as HFpEF without naming sex and dose.

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Source preprint

Nitric oxide synthase inhibition and biological sex define different cardiac responses to cardiometabolic stress in older mice.

10.64898/2026.08.28.747952

Sun JM, Riquileme AT, Hor J, Donner DG, Kiriazis H, Walker SM, Bond S, Mellet NA, Meikle PJ, Parslow AC, Huang ML, Kanki M, Drew BG, Tham YK, McMullen JR, Young MJ.

Open on biorxiv →PDF

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