Growth hormone releasing peptide-6 (GHRP-6) and other related secretagogue synthetic peptides: A mine of medical potentialities for unmet medical needs

Despite intense basic research and numerous novel therapies under clinical investigation, cardioprotection as principal pharmacological indication remains as an empty niche. We have rigorously reviewed the investigational development of growth hormone releasing peptides (GHRP) and their clinical niching perspectives. GHRP constitute a group of small synthetic peptides that stimulate the growth hormone secretion and downstream axis activity. Two well-characterized peptidyl secretagogues receptors (GHSR 1a and CD36) are broadly represented including the cardiovascular system. Early studies translated into a new research era that inserted synthetic GHRP as promising cardio and cytoprotective candidates. A broad safety profile and a successful preclinical pharmacology nurtured the enthusiasm before one of these GHRP family members (GHRP-6) as a myocardial reperfusion damages-attenuating candidate. The existence of efficacious although occasional and fragmented clinical interventions in life-threatening conditions, along with the GHRP-6 multifactorial mechanism of action in myocardial infarction, ignite the initiative for a coherent clinical development. Abbreviations: AKT: Protein kinase B, AMI: acute myocardial infarction, ApoE: Apolipoprotein E, CTGF: Connective tissue growth factor, DCM: dilated cardiomyopathy, dP/dt: indicates the rate of left ventricle maximal pressure rise in early systole. In general is a measure of left ventricle global contractility. DX: doxorubicin, ECM: Extracellular matrix, EGF: epidermal growth factor, ERK1/2: Extracellular signal-regulated kinase 1/2, GH: Growth hormone, GHRH: Growth hormone–releasing hormone, GHRP: Growth hormone releasing peptides, GHS: Growth hormone secretagogues, GHS-R: Growth hormone secretagogue receptor, GHSR-1a: Growth hormone secretagogue receptor type 1a, HIF-1α: hypoxia-inducible factor-1 alpha, I/R: ischemia and reperfusion, IGF-1: insulin-like growth factor-1, IL-1β: Interleukin-1 beta, IL-6: Interleukin 6, LPS: lipopolysacharide, LV: left ventricle, LVEF: left ventricular ejection fraction, MBP: mean blood pressure, MIF: macrophage migration inhibitory factor, MCP-1: Monocyte chemoattractant protein-1, MMP: matrix metalloproteinase, MOD: Multiple Organs Damage, NEP: nitrosylation end-products, NIH: National Institutes of Health, PDGF: Platelet-derived growth factor, PGC1α: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha, PI-3K: Phosphatidylinositol-4,5-bisphosphate 3-kinase, PPARγ: Peroxisome proliferator-activated receptor gamma, p-PLB: phosphorylated phospholamban, RAS: Renin-angiotensin system, rhGH: recombinant human growth hormone, ROS: reactive oxygen species, TGF-β: Transforming growth factor beta, TIMP: tissue inhibitor of metalloproteinase, TNF-alpha: Tumor necrosis factor alpha.