TP508 (Chrysalin) reverses endothelial dysfunction and increases perfusion and myocardial function in hearts with chronic ischemia. Academic Article uri icon

abstract

  • Endothelial dysfunction (ED) is characterized by impaired nitric oxide (NO) signaling, decreased NO-dependent vasodilatation, increased vascular inflammation, and diminished response to angiogenic factors. TP508 (Chrysalin), an angiogenic tissue repair peptide, was tested for potential effects on myocardial revascularization and ED using a porcine model of chronic myocardial ischemia. TP508 increased perfusion in ischemic regions up to16-fold (P < .02) and doubled myocardial wall thickening (P < .02) relative to placebo controls. Ischemic arterioles exhibited impaired NO-mediated vasodilation and diminished NO production. TP508 reversed ischemic effects, increasing NO-mediated vasodilation (P < .05), endothelial nitric oxide synthase (eNOS) expression, and NO production. In human endothelial cells, TP508 stimulated eNOS activation (1.84 +/- 0.2-fold; P < .02), increased NO production (85 +/- 18%; P < .02), and prevented hypoxia-induced eNOS downregulation (P < .01). Thus, TP508 reverses ED both in porcine ischemic hearts and cultured human endothelial cells. These results suggest potential therapeutic benefit of TP508 in myocardial revascularization and treatment of ED-related diseases.

published proceedings

  • J Cardiovasc Pharmacol Ther

altmetric score

  • 7

author list (cited authors)

  • Fossum, T. W., Olszewska-Pazdrak, B., Mertens, M. M., Makarski, L. A., Miller, M. W., Hein, T. W., ... Carney, D. H.

citation count

  • 16

complete list of authors

  • Fossum, Theresa W||Olszewska-Pazdrak, Barbara||Mertens, Michelle M||Makarski, Lori A||Miller, Matthew W||Hein, Travis W||Kuo, Lih||Clubb, Fred||Fuller, Gerald M||Carney, Darrell H

publication date

  • September 2008