Key result
PNU-282,987 improves cardiac function and attenuates myocardial fibrosis via SIRT3 in ischemic cardiomyopathy models.
Why the study?
The role of α7-nicotinic acetylcholine receptor activation in attenuating ischemic cardiomyopathy via regulation of EndMT and involvement of SIRT3 was unclear.
Does PNU-282,987 improve cardiac function and attenuate myocardial fibrosis in rats with ischemic cardiomyopathy and HUVECs?
Does PNU-282,987 improve cardiac function and attenuate myocardial fibrosis in rats with ischemic cardiomyopathy and HUVECs?
Activation of α7-nAChR attenuates ischemic cardiomyopathy and myocardial fibrosis through a SIRT3-dependent modulation of EndMT in preclinical models.
Answers are grounded in this paper and cite their sources.
α7-nAChR agonism merits human ICM trials; hypothesis-generating for SIRT3-EndMT targeting in ischemic cardiomyopathy.
To investigate whether α7-nicotinic acetylcholine receptor (α7-nAChR) activation attenuates ischemic cardiomyopathy (ICM) through regulation of endothelial-to-mesenchymal transition (EndMT), and to explore the involvement of Sirtuin-3 (SIRT3) in this process. ICM was induced in rats by coronary ligation for 4 weeks, followed by treatment with PNU-282,987, a selective α7-nAChR agonist, or cardiac-specific SIRT3 knockdown using serotype 9 adeno-associated virus (AAV9). Human umbilical vein endothelial cells (HUVECs) were treated with transforming growth factor-β (TGF-β) and/or PNU-282,987 (10 µM). α7-nAChR activation improved cardiac function, reversed ICM-induced TGF-β upregulation and SIRT3 downregulation, and inhibited EndMT-related changes. These effects were weakened by SIRT3 knockdown. The findings suggest that α7-nAChR activation alleviates ICM and myocardial fibrosis through a SIRT3-dependent mechanism, although direct receptor-level specificity requires further validation.
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He et al. (2026) studied Ischemic cardiomyopathy (ICM). PNU-282,987 (α7-nAChR agonist) vs. Untreated controls / SIRT3 knockdown was evaluated on Cardiac function, TGF-β expression, SIRT3 expression, and EndMT-related changes. Treatment with 10 µM PNU-282,987 over 4 weeks activated α7-nAChR, improving cardiac function and attenuating myocardial fibrosis via a SIRT3-dependent mechanism in rat models of ischemic cardiomyopathy.
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