Removal of low-density lipoprotein from plasma by adsorption increases bradykinin and plasma nitric oxide levels in patients with peripheral atherosclerosis.
Low-density lipoprotein (LDL) adsorption using a dextran sulfate cellulose column is brought about by electrostatic binding between the positive charges of apolipoprotein B in LDL and the negative charges of dextran sulfate cellulose. There is general agreement that the initial contact phase in the coagulation pathway may be activated by a negatively charged surface such as dextran sulfate cellulose, resulting in the generation of bradykinin. We investigated whether the increase in the generation of bradykinin during LDL adsorption is accompanied by the activation of endogenous production of nitric oxide (NO) in patients with peripheral atherosclerosis. LDL adsorption therapy was repeated ten times over a period of 3 months in ten peripheral atherosclerosis patients. Treatment significantly reduced serum total cholesterol and LDL cholesterol levels. This was associated with a significant improvement in Fontaine's classification and ankle pressure index. We also measured the kinin-kallikrein system and plasma levels of NO in the same patients. The results showed that coagulation factors of the intrinsic pathway including high-molecular-weight kininogen and prekallikrein decreased markedly after initial adsorption compared with the levels before treatment. There was a marked increase in bradykinin and NO concentrations after the initial adsorption, compared with their levels before adsorption. Our results suggest that the generation of bradykinin and increased plasma levels of NO may contribute to the improvement in peripheral circulation after LDL adsorption in peripheral atherosclerosis patients.
Murashima
J
J
Department of Internal Medicine, Sasebo Chuo Hospital, Japan.
Ueki
Y
Y
Matsunaga
Y
Y
Yano
M
M
Matsumoto
K
K
Miyake
S
S
Tominaga
Y
Y
Eguchi
K
K
Yano
K
K
D000327:Adsorption; D000368:Aged; D001161:Arteriosclerosis / Q000097:blood / Q000628:therapy*; D001920:Bradykinin / Q000097:blood*; D002482:Cellulose; D016264:Dextran Sulfate; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D008077:Lipoproteins, LDL / Q000097:blood*; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000628:therapy*; D010956:Plasmapheresis / Q000379:methods
D007202:Indicators and Reagents; D008077:Lipoproteins, LDL; D009569:Nitric Oxide; D002482:Cellulose; D016264:Dextran Sulfate; D001920:Bradykinin