The effects of a growth hormone-releasing hormone antagonist and a gastrin-releasing peptide antagonist on intimal hyperplasia of the carotid artery after balloon injury in a diabetic rat model

John C. Moscona, Matthew N. Peters, Andrew V Schally, Sudesh Srivastav, Patrice Delafontaine, Anand Irimpen

Research output: Contribution to journalArticle

Abstract

Introduction Arterial restenosis after angioplasty/stenting has hindered coronary artery disease treatment, especially in diabetics. We theorized that gastrin-releasing peptide (GRP) antagonists and growth hormone-releasing hormone (GHRH) antagonists might decrease neointimal hyperplasia and restenosis in diabetic rats after common carotid arterial balloon injury. Methods Two separate experiments were conducted to test the effects of a GRP antagonist (RC-3095) and a GHRH antagonist (MZ-4-71) on vascular smooth muscle (VSM) growth. In a preliminary in vitro experiment non-injured human aortic vascular smooth muscle (VSM) proliferation was compared between growth media and control. In a second in vivo experiment, intimal and medial area, intima/media ratio (IM) and percent stenosis were compared between injured carotid arteries in twelve Zucker type II obese rats treated with subcutaneously injected RC-3095, MZ-4-71, or control media. Results In the in vitro experiment, decreased VSM cell growth was observed in GRP antagonist (p < 0.05) and GHRH antagonist groups (p < 0.05) compared to the control group. In the in vivo experiment, the GRP antagonist group had a decreased IM ratio (1.63 ± 0.41, p < 0.05) and an increased area of stenosis (98.78% ± 1.48 p = NS) compared to control (2.38 ± 1.09) while the GHRH antagonist group had decreased IM ratio (1.33 ± 0.58 SD, p < 0.05) and percent area of stenosis (78.84% ± 24.97, p < 0.05) compared to control (2.38 ± 1.09). Conclusions The significant decrease in both IM ratio and percent area of stenosis in the GHRH antagonist group supports the hypothesis that this peptide may reduce neointimal hyperplasia and restenosis.

Original languageEnglish (US)
Pages (from-to)56-64
Number of pages9
JournalArtery Research
Volume19
DOIs
StatePublished - Sep 1 2017

Keywords

  • Arterial restenosis
  • Diabetes mellitus
  • Gastrin-releasing peptide antagonist
  • Growth hormone-releasing hormone antagonist
  • Neointimal hyperplasia

ASJC Scopus subject areas

  • Anatomy
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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