Angiotensin II-derived reactive oxygen species promote angiogenesis in human late endothelial progenitor cells through heme oxygenase-1 via ERK1/2 and AKT/PI3K pathways

Inflammation. 2014 Jun;37(3):858-70. doi: 10.1007/s10753-013-9806-9.

Abstract

Angiotensin II (Ang II), the main component of renin-angiotensin system, could mediate pathogenic angiogenesis in cardiovascular disorders. Late endothelial progenitor cells (EPCs) possess potent self-renewal and angiogenic potency superior to early EPCs, but few study focused on the cross-talk between Ang II and late EPCs. We observed that Ang II could increase reactive oxygen species (ROS) and promote capillary formation in late EPCs. Ang II-derived ROS could also upregulate heme oxygenase-1 (HO-1) expression, and treating late EPCs with HO-1 small interfering RNA or heme oxygenase inhibitor (HO inhibitor) could inhibit Ang II-induced tube formation and increase ROS level and apoptosis rate. In addition, PD98059 and LY294002 pretreatment attenuated Ang II-induced HO-1 expression. Accordingly, Ang II-derived ROS could promote angiogenesis in late EPCs by inducing HO-1 expression via ERK1/2 and AKT/PI3K pathways, and we believe HO-1 might be a promising intervention target in EPCs due to its potent proangiogenic, antioxidant, and antiapoptosis potentials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / metabolism*
  • Antioxidants
  • Apoptosis
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Cells, Cultured
  • Chromones / pharmacology
  • Endothelial Progenitor Cells / physiology*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Flavonoids / pharmacology
  • Heme Oxygenase-1 / antagonists & inhibitors
  • Heme Oxygenase-1 / biosynthesis*
  • Heme Oxygenase-1 / genetics
  • Humans
  • Morpholines / pharmacology
  • Neovascularization, Physiologic / physiology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference
  • RNA, Small Interfering
  • Reactive Oxygen Species / metabolism*

Substances

  • Antioxidants
  • Chromones
  • Flavonoids
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • Angiotensin II
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • Proto-Oncogene Proteins c-akt
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Extracellular Signal-Regulated MAP Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one