GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Ghrelin ameliorates impaired angiogenesis of ischemic myocardium through GHSR1a-mediated AMPK/eNOS signal pathway in diabetic rats.
Wang. Li L; Chen. Qingwei Q; Li. Guiqiong G; Ke. Dazhi D
Key Findings
- Ghrelin treatment improved left‑ventricular function and reduced infarct size in diabetic rats after myocardial infarction.
- Ghrelin increased microvascular density and boosted expression of HIF‑1α, VEGF, Flk‑1, Flt‑1, and phosphorylation of AMPK and eNOS.
- Blocking the GHSR‑1a receptor with [D‑Lys3]‑GHRP‑6 completely stopped ghrelin’s beneficial effects, confirming the pathway’s dependence on GHSR‑1a.
Practical Outcomes
- The study suggests that activating the ghrelin/GHSR‑1a pathway (for example with GHRP‑6) could support heart blood‑vessel growth and recovery, especially under diabetic or metabolic stress. However, the work is in rats, uses high intraperitoneal doses, and human dosing or safety is unknown, so biohackers should treat this as a mechanistic hint rather than a ready‑to‑use protocol.
Summary
In diabetic rats that had a heart attack, giving the hormone ghrelin helped the heart pump better, reduced the size of the damaged area, and grew more tiny blood vessels. It did this by turning on a chain of signals (HIF‑1α, VEGF, its receptors, AMPK and eNOS). When a drug that blocks the ghrelin receptor was added, all the good effects disappeared, showing the benefits depend on that receptor.
Abstract
Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor (GHSR), has been found to stimulate angiogenesis in vivo and in vitro. However, the effect and the corresponding mechanisms of ghrelin on impaired myocardial angiogenesis in diabetic and myocardial infarction (MI) rat model are still unknown. In the present study, adult SD rats were randomly divided into 4 groups: control, DM, DM+ghrelin, DM+ghrelin+[D-Lys3]-GHRP-6 groups. DM was induced by streptozotocin (STZ) 60 mg/kg body weight. 12 weeks post STZ injection all groups were subjected to MI, which was induced by ligation left anterior descending artery (LAD). Ghrelin and [D-Lys3]-GHRP-6 were administered via intraperitoneal injection at the doses 200 μg/kg and 50mg/kg for 4 weeks, respectively. Left ventricular function, microvascular density (MVD), myocardial infarct size, the expression of hypoxia-inducible factor (HIF1α), vascular endothelial growth factor (VEGF), fetal liver kinase-1 (Flk-1) and fms-like tyrosine kinase-1 (Flt-1), AMPK and endothelial nitric oxide synthase (eNOS) phosphorylation were examined. Compared with the DM group, left ventricular ejection fraction (LVEF), fractional shortening (FS), and MVD were increased, whereas myocardial infarct size decreased remarkably in DM+ghrelin group. For the mechanism study, we found that ghrelin promoted the HIF1α, VEGF, Flk-1 and Flt-1 expression, AMPK and eNOS phosphorylation in diabetic rats. However, the above biochemical events in ghrelin treated diabetic rats were completely inhibited by GHSR-1a blocker [D-Lys3]-GHRP-6. These results suggest that administration of ghrelin ameliorates impaired angiogenesis in diabetic MI rats. And these beneficial effects derive from regulating GHSR1a-mediated AMPK/eNOS signal pathway by upregulating of HIF1α, VEGF and its receptors Flk-1, Flt-1 expressions.
Study Information
pubmed
2015
2015-09-10T00:00:00.000Z
10.1016/j.peptides.2015.09.004
25
59