Growth Hormone-Releasing Peptide-6 (GHRP-6) Ameliorates Post-Infarct Ventricular Remodeling and Systolic Dysfunction
Linlin Wang1, Arielis Rodriguez-Ulloa2, Jorge Berlanga-Acosta2
1Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Insights
Growth Hormone Releasing Peptide-6 (GHRP-6) shows significant cardioprotective effects, reducing heart damage and improving function after myocardial infarction. This peptide may offer a novel therapeutic strategy for ischemic heart conditions.
Area of Science:
- Cardiology
- Molecular Biology
- Pharmacology
Background:
- Growth Hormone Releasing Peptide-6 (GHRP-6) is a hexapeptide secretagogue with demonstrated cardioprotective potential.
- A minimum effective dose of 0.4 mg/kg for enhancing inotropy was previously established.
- A rat model of non-reperfusion myocardial infarction was utilized to assess GHRP-6's effects.
Purpose of the Study:
- To evaluate the cardioprotective effects of GHRP-6 in a myocardial infarction model.
- To investigate the underlying molecular mechanisms of GHRP-6's protective action.
Main Methods:
- Rats were divided into sham-operated, infarcted + saline control, and infarcted + GHRP-6 treated groups.
- Treatments were administered for 7 days post-surgery, followed by echocardiographic and histological evaluation.
- Mitochondrial proteomic analysis was performed on healthy rats treated with GHRP-6 or saline.
Main Results:
- GHRP-6 treatment significantly attenuated myocardial tissue death and reduced interstitial fibrosis.
- Left ventricle physiology was improved following GHRP-6 administration.
- Proteomic analysis suggested GHRP-6's effects are mediated by enhanced fatty acid beta-oxidation, apoptosis prevention, antioxidant defenses, and metabolic reprogramming.
Conclusions:
- GHRP-6 demonstrates potent cardioprotective properties against ischemic injury.
- The peptide effectively mitigates both morphological and functional deficits post-myocardial infarction.
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.
