Anti-salusin-β antibody enhances angiogenesis after myocardial ischemia reperfusion injury

Expert Opin Ther Targets. 2013 Sep;17(9):1003-9. doi: 10.1517/14728222.2013.819852. Epub 2013 Jul 19.

Abstract

Backgrounds: Salusins are multifunctional endogenous bioactive peptides simultaneously biosynthesized from their precursor prosalusin. Salusin-β stimulates proliferation of vascular smooth muscle cells and fibroblasts and regulates myocardial growth and hypertrophy. Salusin-β has potent hypotensive, bradycardic and proatherosclerotic effects.

Objectives: To investigate whether salusin-β plays a role in myocardial remodeling after myocardial ischemia reperfusion (I/R) injury, rat I/R models were created by the left anterior descending coronary artery occlusion for 30 min, followed by 24 h or 7 days of reperfusion (control, n = 6 each).

Results and conclusion: Immunohistochemical double staining showed the enhanced expression of salusin-β in the macrophages around myocardial ischemic area. Anti-salusin-β treated groups were administered the neutralizing salusin-β antibody (10 μl/day, i.p.) once daily from day -1 to day 1 or from day -1 to day 7 (anti-salusin-β, n = 6 each). The anti-salusin-β therapy enhanced myocardial angiogenesis in the peri-ischemic area of reperfusion. The small vessels (< 40 μm in diameter) of I/R hearts treated with anti-salusin-β were more densely populated than those of control animals (108.5 ± 19.7 vs 47.5 ± 2.4, p < 0.05). Real-time PCR revealed that the anti-salusin-β therapy-induced angiogenesis was not associated with enhanced vascular endothelial growth factor A expression. The authors, for the first time, have clarified that endogenous salusin-β suppresses angiogenesis which is critical in the development of cardiac remodeling following I/R injury.

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Antibodies / therapeutic use*
  • Cell Line
  • Cells, Cultured
  • Chemokine CCL2 / genetics
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / immunology*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Interleukin-8 / genetics
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 9 / genetics
  • Myocardial Reperfusion Injury / drug therapy*
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardium / metabolism
  • Neovascularization, Physiologic / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Antibodies
  • Ccl2 protein, rat
  • Chemokine CCL2
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-8
  • Vascular Endothelial Growth Factor A
  • salusin-beta, rat
  • vascular endothelial growth factor A, rat
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat