Release of proinflammatory mediators and expression of proinflammatory adhesion molecules by endothelial progenitor cells

Yanmin Zhang, David Ingram, Michael Murphy, M. Reza Saadatzadeh, Laura E. Mead, Daniel N. Prater, Jalees Rehman

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Cell therapy with endothelial progenitor cells (EPCs) is an emerging therapeutic option to promote angiogenesis or endothelial repair. Although the release of angiogenic paracrine factors is known to contribute to their therapeutic effect, little is known about their release of proinflammatory factors and expression of proinflammatory adhesion molecules. "Early" EPCs and "late" EPCs were isolated from human peripheral blood and their release of chemokines and thromboinflammatory mediators as well as their expression of the proinflammatory adhesion molecules was assessed at baseline and with stimulation. The effect of simvastatin on monocyte chemoattractant protein-1 (MCP-1) secretion by late EPCs from patients with vascular disease was also evaluated. All groups of EPCs released chemokines and thromboinflammatory mediators. Early EPCs primarily released thromboinflammatory mediators such as tissue factor (0.5 ± 0.1 ng/million cells, P < 0.05), whereas adult late EPCs primarily released chemokines such as MCP-1 (287 ± 98 ng/million cells, P < 0.05). Stimulation with tumor necrosis factor (TNF)-α augmented the expression of proinflammatory adhesion molecules and paracrine factors by all EPC subtypes. The release of MCP-1 by late EPCs was markedly reduced by simvastatin treatment of the cells. All EPC subtypes expressed proinflammatory paracrine factors and adhesion molecules involved in atherosclerosis. Future clinical studies should therefore not only assess the efficacy of EPCs but also monitor inflammatory activation following EPC transplantation in patients. Pharmacological modulation of EPCs before and after transplantation may represent a novel approach to improve their safety.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume296
Issue number5
DOIs
StatePublished - May 2009

Fingerprint

Chemokine CCL2
Chemokines
Simvastatin
Endothelial Progenitor Cells
Angiogenesis Inducing Agents
Cell Transplantation
Thromboplastin
Therapeutic Uses
Cell- and Tissue-Based Therapy
Vascular Diseases
Atherosclerosis
Tumor Necrosis Factor-alpha
Transplantation
Pharmacology
Safety
Therapeutics

Keywords

  • Cardiovascular cell therapy
  • Endothelial progenitor cells
  • Inflammation

ASJC Scopus subject areas

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

Cite this

Release of proinflammatory mediators and expression of proinflammatory adhesion molecules by endothelial progenitor cells. / Zhang, Yanmin; Ingram, David; Murphy, Michael; Saadatzadeh, M. Reza; Mead, Laura E.; Prater, Daniel N.; Rehman, Jalees.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 296, No. 5, 05.2009.

Research output: Contribution to journalArticle

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