Mechanical, cellular, and molecular factors interact to modulate circulating endothelial cell progenitors

Area of Science:

• Cardiovascular Biology
• Cellular and Molecular Medicine
• Hematology

Background:

• Two classes of human circulating endothelial cell (EC) progenitors exist: CD34+ and CD34-CD14+ cells.
• CD34-CD14+ monocytic cells are more abundant and may be the primary circulating EC progenitor type.
• Factors regulating CD34-CD14+ EC progenitor function are largely unknown, but environmental stimuli like hypoxia and stretch likely play a role.

Purpose of the Study:

• To investigate the impact of hypoxia and stretch on EC production by CD34-CD14+ progenitors.
• To determine how cardiovascular cells and peripheral blood mononuclear cells modulate EC progenitor function.

Main Methods:

• Evaluation of EC production in CD34-CD14+ cell cultures.
• Analysis of conditioned media (CM) from stretched coronary artery smooth muscle cells and hypoxic cardiomyocytes.
• Assessment of EC progenitor responses to CM in the presence of CD34-CD14- peripheral blood mononuclear cells (PBMCs) and angiogenic factors.

Main Results:

• Neither stretch nor hypoxia directly altered EC production by progenitors, but indirectly via cardiovascular cells.
• CM from stretched smooth muscle cells inhibited EC production, while CM from hypoxic cardiomyocytes increased EC number.
• CD34-CD14- PBMCs altered progenitor responses to CM, attenuated responses to angiogenic factors (FGF-2, VEGF-A165, EPO), and induced cell death with TGF-β1.

Conclusions:

• CD34-CD14+ cells are significant EC progenitors whose function is modulated by the cardiovascular microenvironment.
• Peripheral blood mononuclear cells significantly impact EC progenitor behavior, influencing their response to angiogenic stimuli and survival factors.
• Understanding these interactions is crucial for developing therapies targeting angiogenesis and vascular repair.