Effects of Cilostazol on Vascular Endothelial Growth Factor , Inflammatory and Oxidative Stress Biomarkers in Hemodialysis Patients With Peripheral Vascular Disease.

Purpose :

Patients with end stage renal disease are at an increased risk for cardiovascular disease (CVD) and the annual mortality from CVD in end-stage renal disease (ESRD) patients is substantially higher than in the general population. Peripheral arterial disease (PAD), the most common manifestation of atherosclerosis, is characterized by atherosclerotic occlusive disease of the lower extremities. The most common symptom of PAD is intermittent claudication, defined as pain, cramping, or aching in the calves, thighs, or buttocks. However, it has been reported that over one-half of those with PAD remains asymptomatic. Rest pain, tissue loss, and gangrene are among the more extreme presentations of PAD and PAD has been a major cause for lower-extremity amputation, especially in those HD patients with diabetes. However, few available data stressed on the huge burden of PAD in hemodialysis (HD) patients. More importantly, presence of PAD in these patients is an important predictor for subsequent cardiovascular and overall mortality. The medical therapy of in PAD in general population is limited to a few antiplatelet drugs and statin in relatively few descriptive studies and randomized control trials. There are no appropriate randomized trials of these therapies in the treatment of PAD in patients with chronic kidney diseases. Hence, there are as yet no substantial data to support for efficacy of pharmacologic interventions of PAD in these specific groups of patients.

Hypothesis

Use of cilosatzol may be associated with increased plasma levels of VEGF and TF and amelioration of inflammation in HD patients with PAD.to perform a parallel, controlled trial to examine the effect of cilostazol treatment on plasma VEGF levels, tissue factors , inflammatory markers (such as IL-6, hsCRP) levels, oxidative stress markers in ESRD patients with PAD.

Many human diseases are characterized by disorders of the vasculature. In ischemic heart disease or peripheral artery disease, insufficient blood vasculature leads to tissue ischemia. Out of the many players in the angiogenesis field, the vascular endothelial growth factors are by far the best characterized and several VEGFs have already entered clinical use in a variety of human conditions. While many studies have addressed the role of angiogenesis and the blood vasculature in human physiology and pathology, the role of proangiogenic therapy in PAD has until recently attracted very little attention. VEGF is the prime hypoxia inducible angiogenic factor and binds VEGFR-1 and VEGFR-2. VEGF increases permeability of the endothelium through the formation of intercellular gaps, vesico-vascular organelles, vacuoles as well as fenestrations. VEGF also causes vasodilatation through the induction of the endothelial nitric oxide synthase (eNOS) and the subsequent increase in nitric oxide production. In recent years, several studies have reported beneficial effects of VEGF when used as a proangiogenic therapy in the setting of tissue ischemia. While proangiogenic therapies could be employed in the treatment of various ischemic diseases,controlling these processes with targeted molecular therapies remains at the heart of research.