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Growth Hormone-Releasing Peptide-6 (GHRP-6) Ameliorates Post-Infarct Ventricular Remodeling and Systolic Dysfunction in a Model of Permanent Coronary Ligation.

Wang L, Rodriguez-Ulloa A, Berlanga-Acosta J, García-Ojalvo A, Abreu-Cruz A, Gonzalez-López LJ, Besada-López V, Ramos-Gómez Y, Guillén-Nieto G, Jiang B.
Pharmaceuticals (Basel, Switzerland) · March 12, 2026
Plain-language summary

This animal study investigated whether Growth Hormone-Releasing Peptide-6 (GHRP-6), a GH secretagogue hexapeptide, could reduce cardiac damage following myocardial infarction. Using a permanent left coronary artery ligation model in rats (a non-reperfusion model), researchers divided animals into three groups: sham-operated controls, infarcted rats treated with saline, and infarcted rats treated with GHRP-6. Treatment began post-surgery and continued for seven days. Outcomes were assessed via echocardiography and histology on day seven. A separate cohort of twelve healthy rats was used for mitochondrial proteomic analysis six hours after compound administration. The study found that, compared to the saline-treated infarcted group, GHRP-6-treated rats showed reduced myocardial tissue loss, less interstitial fibrosis and scarring, and improved left ventricular function. Proteomic data suggested that potential mechanisms may include upregulation of fatty acid beta-oxidation, apoptosis-prevention pathways, antioxidant defenses, and mitochondrial metabolic reprogramming. Key limitations include the exclusive use of an animal model, a short seven-day observation window, a small sample size, and the mechanistic proteomic findings being derived from healthy rather than infarcted animals. No human data were generated.

Why this grade: All experimental data were collected exclusively in a rat coronary ligation model with no human subjects, clinical trial components, or direct translation to human physiology.

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Abstract

Background/Objective : GHRP-6 is a GH secretagogue hexapeptide with expanding and promising cardioprotective effects. Having determined 0.4 mg/kg as the minimum effective dose for enhancing inotropy based on echocardiographic parameters in healthy rats, we implemented a non-reperfusion myocardial infarct model, with its consequent left ventricle wall thinning and ballooning, via permanent left descending coronary artery ligation. Methods : Rats were assigned to three groups: sham-operated/normal rats, infarcted + saline-treated control rats, and infarcted + GHRP-6-administration rats. Treatments were initiated post-surgery and continued for 7 days. On day 7, the animals were echocardiographically and histologically evaluated. For mitochondrial proteomic analysis, an additional 12 healthy rats were used. Six animals received GHRP-6 or normal saline and were observed for 6 h after the inoculation. Results : Here, we show that GHRP-6 attenuated myocardial tissue demise, reduced myocardial interstitial fibrosis/scarring, and integrally improved left ventricle physiology. The proteomic analysis indicated that the GHRP-6 cardioprotective effects may be theoretically mediated by the concerted upregulation of proteins/pathways involved in fatty acid beta-oxidation, apoptosis prevention pathways, antioxidant defenses, and mitochondrial metabolic reprogramming. Conclusions : GHRP-6 is a potent cardioprotective candidate attenuating morphological and functional outcomes caused by late ischemia.

Educational summary of published research — not medical advice. License: cc by. Full text is shown only where licensing permits.