Alterations of bone marrow-derived endothelial progenitor cells following acute pulmonary embolism in mice

Exp Biol Med (Maywood). 2010 Aug;235(8):989-98. doi: 10.1258/ebm.2010.010057.

Abstract

Pulmonary embolism (PE) is a common, lethal, ischemic disease. PE-induced endothelium injury plays a critical role in the pathophysiological consequences of PE. Endothelial progenitor cells (EPCs) can be mobilized from the bone marrow to enter circulation and play important roles in repair of damaged endothelium. However, it is not yet known if EPC mobilization results from PE. The alterations of the quantity and function of bone marrow-derived EPCs were detected in acute pulmonary embolism (APE) events in mice, and the possible role of the endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) pathway in those alterations was explored. APE models were established by injection of autologous thrombi into the right jugular vein of C57BL/6 mice. Mice were divided into sham and experimental groups including one hour (1H), one day (1D) and two day (2D) groups after injection. The results showed that in the APE 1D group, the thrombi were easily found in the large or medium pulmonary vessel. And CD133(+) or CD34(+) cells in bone marrow increased significantly, while CD133(+)/vascular endothelial growth factor receptor 2(+) EPCs decreased. After seven days in culture, the abilities of incorporation into a vascular network, adhesion to fibronectin, migration and proliferation of bone marrow-derived EPCs in the APE 1D group increased significantly. The mRNA and protein expression levels of eNOS in EPCs increased in the APE 1D group. Treatment of EPCs with N(G)-nitro-L-arginine methyl ester inhibited functional alterations induced by APE. The results suggested that APE events stimulate the mobilization of EPCs from bone marrow, and enhance their functions. The eNOS/NO pathway may be involved in this process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Acute Disease
  • Animals
  • Antigens, CD / metabolism
  • Antigens, CD34 / metabolism
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / metabolism
  • Cell Adhesion
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Endothelium / cytology*
  • Endothelium / metabolism
  • Flow Cytometry
  • Glycoproteins / metabolism
  • Immunochemistry
  • Mice
  • Mice, Inbred C57BL
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / metabolism
  • Peptides / metabolism
  • Pulmonary Embolism / metabolism
  • Pulmonary Embolism / pathology*
  • Stem Cells / cytology*
  • Stem Cells / metabolism

Substances

  • AC133 Antigen
  • Antigens, CD
  • Antigens, CD34
  • Glycoproteins
  • Peptides
  • Prom1 protein, mouse
  • Nitric Oxide
  • Nitric Oxide Synthase
  • NG-Nitroarginine Methyl Ester