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Sustained LDL inhibition may contribute to dialysis PAD benefits
11 March 2010
MedWire News: Sustained inhibition of low-density lipoprotein (LDL) may contribute to long-term benefits in dialysis patients with peripheral arterial disease (PAD) who respond to apheresis, Japanese researchers suggest.
LDL apheresis is a potential treatment for PAD resistant to conventional therapy, says the team from Yokohama City University Graduate School of Medicine.
The researchers studied 19 hemodialysis patients with the complication of PAD who underwent 10 sessions of LDL apheresis once or twice a week on nonhemodialysis days.
Absolute walking distance improved significantly from 171 m at baseline to 294 m at the tenth apheresis session and 270 m at 3 months after treatment ended.
Ankle-brachial pressure index (ABI) also significantly improved from a baseline of 0.59 to 0.67 at the tenth apheresis session, the researchers write in the journal Atherosclerosis, Thrombosis, and Vascular Biology.
Based on ABI at 3 months after treatment ended, participants were classified into 10 responders with improved ABI and nine nonresponders with worsened ABI.
In responders, the first apheresis was associated with a reduction in circulating levels of oxidized LDL, C-reactive protein, and fibrinogen compared with baseline. However, none of these changes remained significant at the tenth session or 3 months after treatment.
In vitro tests revealed that responder serum showed increased expression of activated endothelial nitric oxide synthase (eNOS) protein and proliferative activity in human umbilical vein endothelial cells (HUVECs) at the tenth apheresis session compared with baseline.
Kouichi Tamura and colleagues also report a significant correlation between ABI and activated eNOS protein level in HUVECs treated with responder serum.
They conclude: “The results of the present study suggest that the long-term therapeutic effects of LDL apheresis on patients with end-stage renal disease who have PAD are at least partly dependent on the sustained reduction of oxidized LDL and inflammatory stress, along with the activated eNOS-mediated improvement of endothelial cell function.”
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