Objective-Low-density lipoprotein (LDL) apheresis is a potential therapy for conventional therapy-resistant peripheral artery disease. In the present study, we examined the chronic effects of LDL apheresis on clinical parameters in vivo and endothelial cell functions in vitro in hemodialysis patients who had the complication of peripheral artery disease. Methods and Results-Twenty-five patients were enrolled, and the responses of 19 patients to LDL apheresis were analyzed. Patients were classified into 2 groups according to change in ankle-brachial pressure index (ABI) after treatment: patients with improved ABI (responders, nϭ10) and patients with worsened ABI (nonresponders, nϭ9). In the responders, apheresis resulted in a long-term reduction of circulating levels of oxidized LDL, C-reactive protein, and fibrinogen. In human umbilical vein endothelial cells (HUVECs), the serum from the responders increased expression of activated endothelial nitric oxide synthase protein and proliferative activity. Key Words: atherosclerosis Ⅲ endothelium Ⅲ nitric oxide synthase Ⅲ oxidized lipids Ⅲ peripheral arterial disease Ⅲ lipoproteins Ⅲ oxidative stress C ardiovascular disease is the primary cause of death in patients with end-stage renal disease. Patients on dialysis are reported to have a 10 -20-fold greater risk of cardiovascular disease-associated mortality than the general population after stratification for age, gender, race, and the presence or absence of diabetes. Patients undergoing dialysis have many of the risk factors for atherosclerosis, such as hypertension, dyslipidemia, and disturbed calcium-phosphate metabolism, and, indeed, they commonly experience severe atherosclerosis, including peripheral artery disease (PAD). Low-density lipoprotein (LDL) apheresis is a potentially useful treatment for conventional therapy-resistant hypercholesterolemic patients with coronary artery disease and PAD. 1,2 Previously, it was shown that a single LDL apheresis session enhanced the peripheral microcirculation, probably by increasing the production of nitric oxide (NO) and bradykinin, 3 reducing blood viscosity and adhesion molecules, 4 and inducing endothelium-dependent vasodilatation. 5 However, the precise molecular mechanism of the long-term effects of LDL apheresis on the improvement of the peripheral circulation remains unclear and warrants further investigation.We undertook the present study to investigate the shortand long-term effects of LDL apheresis on clinical and laboratory parameters in vivo and vascular endothelial cell function in vitro, in hemodialysis patients with PAD, and to identify factors related to the improvement of the peripheral circulation by LDL apheresis.
Methods
Patients and Study DesignThe study protocol was approved by the Human Ethics Committee of Yokohama City University Hospital. A total of 25 consecutive hemodialysis patients with leg impairments and ankle-