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Nitroglycerin attenuates human endothelial progenitor cell differentiation, function, and survival
Jonathan M DiFabio1, George R Thomas, Liana Zucco
1Division of Cardiology, Department of Medicine, Mount Sinai Hospital, and Department of Pharmacology, University of Toronto, 600 University Ave., Suite 1609, Toronto, ON, Canada M5G 1X5.
The Journal of Pharmacology and Experimental Therapeutics
|April 20, 2006
Summary
Continuous nitroglycerin (glyceryl trinitrate; GTN) therapy may impair endothelial progenitor cells (EPCs). This therapy can negatively affect EPC function, potentially harming recovery from ischemic cardiovascular disease.
Area of Science:
- Cardiovascular Research
- Endothelial Biology
- Cellular Physiology
Background:
- Endothelial progenitor cells (EPCs) are crucial for angiogenesis and response to ischemia.
- Cardiovascular disease and risk factors reduce EPC number, function, and survival.
- Continuous nitroglycerin (glyceryl trinitrate; GTN) therapy can increase oxidative stress, leading to tolerance and endothelial dysfunction, potentially impacting EPCs.
Purpose of the Study:
- To investigate the effects of continuous GTN exposure on circulating human EPC number and function.
- To assess GTN's impact on EPCs both in vivo and during ex vivo expansion.
Main Methods:
- Human EPCs from healthy males were analyzed after 1 week of in vivo GTN exposure or no treatment.
- EPCs were also cultured ex vivo with varying GTN concentrations (100 nM to 1 microM) or without GTN.
- Circulating EPC markers (CD34), apoptosis, differentiation, migration, and mitochondrial activity were assessed.
Main Results:
- In vivo GTN increased circulating CD34+ cells and EPC apoptosis but did not affect differentiation or migration.
- Ex vivo GTN exposure elevated EPC apoptosis and reduced differentiation, migration, and mitochondrial dehydrogenase activity.
- These effects were observed in a dose-dependent manner with increasing GTN concentrations.
Conclusions:
- Continuous GTN therapy may impair critical EPC-mediated processes.
- This impairment of EPC function could be detrimental for patients with ischemic cardiovascular disease.
- Further research is needed to understand the clinical implications of GTN's effects on EPCs.