Impaired PGC-1α-pAMPK signaling in postmenopausal women undergoing cardiac surgery and the role of nicotinamide in its reversal: Insights from a murine model.
Level 3 - non-randomized controlled study
Prospective observational cohort study with human tissue analysis alongside animal experimental model
PubMed 41377471 · doi:10.1016/j.jmccpl.2025.100831
What was done
A prospective cohort study evaluated 102 patients (51 men, 51 women) undergoing cardiac surgery with cardiopulmonary bypass. Investigators compared clinical outcomes (diastolic dysfunction and hospital stay length) and analyzed atrial tissue for proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), phosphorylated AMP-activated protein kinase (pAMPK), and nicotinamide adenine dinucleotide (NAD+) levels. In parallel, an animal model of postmenopausal metabolic dysfunction (ovariectomized mice fed a high-fat diet) was treated with nicotinamide (NAM) to test whether NAD+ precursor supplementation could reverse signaling and functional impairments.
What was found
The abstract reports no specific numerical values, percentages, or effect sizes. Women had a significantly higher incidence of diastolic dysfunction and longer hospital stays than men despite comparable baseline characteristics. Atrial tissue analysis showed increased postoperative PGC-1α and pAMPK in men, whereas women showed decreased expression of both markers and a significant reduction in myocardial NAD+ levels. In ovariectomized mice, NAM supplementation restored myocardial NAD+, elevated PGC-1α expression, and improved systolic and diastolic cardiac function.
Why it matters
This study identifies sex-specific metabolic impairments in myocardial PGC-1α-pAMPK signaling and NAD+ depletion that may explain why postmenopausal women face worse clinical outcomes after cardiac surgery. It highlights NAD+-boosting strategies like nicotinamide as potential non-hormonal therapeutic candidates for heart failure with preserved ejection fraction and surgical cardioprotection.
Limits
The abstract provides no quantitative figures, standard deviations, or p-values. The human study is non-randomized and observational, preventing causal attribution between the molecular deficits and postoperative outcomes. The therapeutic intervention with nicotinamide was evaluated solely in a murine model and not in surgical patients. Sample size for the animal experiments is not reported in the abstract.
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