Fenofibrate effects on endothelial progenitor cell (EPC) number and function

None listed

BACKGROUND AND SCIENTIFIC BASIS Coronary artery disease is an important cause of morbidity and mortality worldwide. Although much is known about the mechanism of myocardial infarction and its associated risk factors, many patients develop myocardial infarction in the absence of known risk factors. Two possible explanations for this are impaired angiogenesis (new blood vessel formation) and impaired endothelial (blood vessel lining) reparative processes in this group of patients. Endothelial progenitor cells (EPC) are thought to be involved in these two processes by: 1) incorporating into new vessels, or 2) coordinating the reparative process. Fenofibrate is a lipid-lowering agent, used in the setting of hypercholesterolemia, particularly among patients with coronary artery disease and diabetes. It has well documented beneficial effects by reducing myocardial infarction. In practice, it is commonly used when patients are intolerant of statins (another cholesterol lowering agent), or in combination with statins. Interest in fenofibrate has increased with recent observations of reduced diabetic microvascular complications. Little is known about EPCs and their function. It has been recently shown that EPCs derived from bone marrow circulate in the peripheral blood and can facilitate the formation of new blood vessels in tissues that are not getting enough blood supply, thereby helping to increase the blood supply to the affected tissue (Asahara T et al Science. 1997;275:964, Urbich C. Circ Res. 2004;95:343). Moreover, patients with coronary artery disease who have high blood levels of EPCs have a better prognosis than those with low EPC levels, possibly due to the beneficial reparative effects of these cells (Werner N. N Engl J Med 2005;353:999). It is unknown if the clinical outcomes of fenofibrate are partly related to EPC levels and function. Statins have been shown to have a positive effect on EPC number and function when used alone. Their effects in combination with fenofibrate have not been evaluated. HYPOTHESIS The central hypotheses of this project are that: 1) EPC levels are increased by fenofibrate 2) EPC levels are higher in those with vascular disease, 3) Fenofibrate augments EPC differentiation and function and 4) Effects of fenofibrate on EPC s occur with and without combination statin therapy. AIMS 1.To determine the number of EPC s after fenofibrate treatment. 2.To investigate if fenofibrate augments EPC function and number. 3.To see the additional benefit of statins on EPC number and function. POTENTIAL SIGNIFICANCE This study will be one of the preliminary studies in man, to identify if fenofibrate has a positive effect on EPCs, and provide an understanding of the clinical effects observed. This will have implications in understanding the role of EPCs in the pathogenesis of vascular diseases, as well as in the development of novel treatment strategies for reducing the impact of vascular disease and myocardial infarction.

No related papers found yet.