Efficacy of a growth hormone-releasing peptide mimetic in cardiac ischemia/reperfusion injury

MacAndrew, J T; Ellery, S S; Parry, Maria A; Pan, Lydia C.; Black, Shawn C.

doi:10.1016/s0014-2999(01)01475-3

Cited by 15 publications

(8 citation statements)

References 39 publications

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“…The results of these previous studies on the effects of GH and recombinant GH on rat MI size, [23][24][25][26] as well as clinical studies on GH replacement for the failing human heart, 15,16 have been controversial, but GHRH and synthetic GHRH-As provide a potential new beneficial strategy for MI and LV dysfunction. 8,9,11,18,27 A B C Figure 6. GHRHR expression.…”

Section: Discussionmentioning

confidence: 99%

Growth Hormone–Releasing Hormone Agonists Reduce Myocardial Infarct Scar in Swine With Subacute Ischemic Cardiomyopathy

Bagno

Kanashiro‐Takeuchi

Suncion

et al. 2015

JAHA

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BackgroundGrowth hormone–releasing hormone agonists (GHRH‐As) stimulate cardiac repair following myocardial infarction (MI) in rats through the activation of the GHRH signaling pathway within the heart. We tested the hypothesis that the administration of GHRH‐As prevents ventricular remodeling in a swine subacute MI model.Methods and ResultsTwelve female Yorkshire swine (25 to 30 kg) underwent transient occlusion of the left anterior descending coronary artery (MI). Two weeks post MI, swine were randomized to receive injections of either 30 μg/kg GHRH‐A (MR‐409) (GHRH‐A group; n=6) or vehicle (placebo group; n=6). Cardiac magnetic resonance imaging and pressure–volume loops were obtained at multiple time points. Infarct, border, and remote (noninfarcted) zones were assessed for GHRH receptor by immunohistochemistry. Four weeks of GHRH‐A treatment resulted in reduced scar mass (GHRH‐A: −21.9±6.42%; P=0.02; placebo: 10.9±5.88%; P=0.25; 2‐way ANOVA; P=0.003), and scar size (percentage of left ventricular mass) (GHRH‐A: −38.38±4.63; P=0.0002; placebo: −14.56±6.92; P=0.16; 2‐way ANOVA; P=0.02). This was accompanied by improved diastolic strain. Unlike in rats, this reduced infarct size in swine was not accompanied by improved cardiac function as measured by serial hemodynamic pressure–volume analysis. GHRH receptors were abundant in cardiac tissue, with a greater density in the border zone of the GHRH‐A group compared with the placebo group.ConclusionsDaily subcutaneous administration of GHRH‐A is feasible and safe in a large animal model of subacute ischemic cardiomyopathy. Furthermore, GHRH‐A therapy significantly reduced infarct size and improved diastolic strain, suggesting a local activation of the GHRH pathway leading to the reparative process.

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Section: Discussionmentioning

confidence: 99%

Growth Hormone–Releasing Hormone Agonists Reduce Myocardial Infarct Scar in Swine With Subacute Ischemic Cardiomyopathy

Bagno

Kanashiro‐Takeuchi

Suncion

et al. 2015

JAHA

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“…Aminophylline (the Bsalt^or complex of theophylline and ethylenediamine), atenolol HCl, and propranolol HCl were purchased from Sigma (St. Louis, MO). Azithromycin, micronized nifedipine, sertraline, trovafloxacin mesylate, CP-331684 1 (a b3 agonist for the treatment of obesity), CP-409092 2 (a GABA a partial agonist developed for the treatment of anxiety), CP-424391 tartrate 3 (a growth hormone secretagogue in clinical trials for the treatment of frailty (13,14)), CJ-013670 mesylate 4 (a 5-lipoxygenase inhibitor with oral activity in animal models of inflammation and airway obstruction (15)) were obtained from Pfizer, Inc. Selected biopharmaceutical properties of the 11 compounds studied are listed in Table I.…”

Section: Methodsmentioning

confidence: 99%

Dog Colonoscopy Model for Predicting Human Colon Absorption

et al. 2006

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“…In the present study, we took advantage of our recent observation that growth hormone-releasing peptides (GHRPs) serve as ligands for CD36 (16) to investigate their effect on atherosclerosis progression in a well-characterized genetic murine model of atherosclerosis. GHRPs consist of small synthetic peptides derived from enkephalin that have been initially developed as growth hormone (GH) secretagogues (17,18) and shown to also exert GH-independent cardiotropic (19,20) and cardioprotective activities, improving postischemic cardiac dysfunction in animal models (21)(22)(23)(24)(25)(26)(27). The identification of CD36 as a GHRP binding site in the heart suggested a role for CD36 in the cardioprotective effects afforded by GHRPs (28).…”

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confidence: 99%

EP 80317, a ligand of the CD36 scavenger receptor, protects apolipoprotein E‐deficient mice from developing atherosclerotic lesions

et al. 2005

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CD36, a type B scavenger receptor expressed on macrophages, appears to play a major role in fatty streak formation through scavenging oxidatively modified lipoproteins in the arterial wall. We tested the hypothesis that EP 80317, a novel CD36 ligand derived from the growth hormone (GH)-releasing peptide family but devoided of any GH releasing activity, exerts anti-atherosclerotic effects in apolipoprotein E-deficient (apoE-/-) mice fed an atherogenic diet from 6 wk of age. Daily subcutaneous injections of EP 80317 (300 microg/kg) or vehicle were initiated at 6, 10, 12, or 14 wk until death at 18 wk. En face analyses of the entire aortic tree revealed a striking reduction (up to 51%) of lesion areas in EP 80317-treated apoE-/- mice compared with controls. Chronic treatment with EP 80317 (12 wk) is also associated with a 30% decrease in total plasma cholesterol, suggesting potential effects of this drug on cholesterol metabolism at the intestine/hepatic levels. EP 80317 exerts both preventive and curative effects on atherosclerotic lesion progression that were shown to be reversible after cessation of treatment. At the macrophage level, EP 80317 reduced oxidized low density lipoproteins internalization and up-regulated genes involved in cholesterol efflux, including peroxisome proliferator-activated receptor gamma (PPARgamma), liver x receptor alpha (LXRalpha), and the ATP binding cassette (ABC) transporters ABCA1 and ABCG1, supporting a role in regulating peripheral cholesterol trafficking. Importantly, the effects of EP 80317 were shown to be CD36 dependent, inasmuch as no anti-atherosclerotic or hypocholesterolemic effects were observed in apoE/CD36 double-deficient mice. In addition, long-term treatment of apoE/CD36 double-deficient mice with EP 80317 did not modulate the expression of genes of the PPARgamma-LXRalpha-ABC transporters pathway. Our results suggest that EP 80317, as a CD36 ligand, might be a prototype for a novel class of anti-atherosclerotic agents.

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Efficacy of a growth hormone-releasing peptide mimetic in cardiac ischemia/reperfusion injury

Cited by 15 publications

References 39 publications

Growth Hormone–Releasing Hormone Agonists Reduce Myocardial Infarct Scar in Swine With Subacute Ischemic Cardiomyopathy

Growth Hormone–Releasing Hormone Agonists Reduce Myocardial Infarct Scar in Swine With Subacute Ischemic Cardiomyopathy

Dog Colonoscopy Model for Predicting Human Colon Absorption

EP 80317, a ligand of the CD36 scavenger receptor, protects apolipoprotein E‐deficient mice from developing atherosclerotic lesions

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