LOW-DENSITY-LIPOPROTEIN ISOLATED FROM PATIENTS WITH ESSENTIAL-HYPERTENSION EXHIBITS INCREASED PROPENSITY FOR OXIDATION AND ENHANCED UPTAKE BY MACROPHAGES - A POSSIBLE ROLE FOR ANGIOTENSIN-II

被引:97
作者
KEIDAR, S [1 ]
KAPLAN, M [1 ]
SHAPIRA, C [1 ]
BROOK, JG [1 ]
AVIRAM, M [1 ]
机构
[1] LADY DAVIES CARMEL HOSP,INST HEART,HAIFA,ISRAEL
关键词
HYPERTENSION; LOW DENSITY LIPOPROTEIN; MACROPHAGE; LIPID PEROXIDATION; ANGIOTENSIN II;
D O I
10.1016/0021-9150(94)90143-0
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In patients with essential hypertension, the increased risk for atherosclerosis is related not only to the blood pressure levels per se, but also to other, unknown, factors. Recent observations have indicated that oxidation of low density lipoprotein (LDL) and macrophage uptake of oxidized LDL are implicated in human atherosclerosis. We tested both the susceptibility of LDL, derived from hypertensive patients, to lipid peroxidation as well as its uptake by. macrophages, in comparison with control LDL obtained from healthy subjects. The LDL that was derived from 25 patients with essential hypertension demonstrated increased propensity for lipid peroxidation with a 63%, 91% and 69% elevation in the content of the lipoprotein malondialdehyde, peroxides and conjugated dienes, respectively, in comparison with control LDL. Minimally modified LDL (MM-LDL) (prepared by 6 months' storage of the LDL at 4 degrees C) derived from the hypertensive patients also demonstrated increased lipid peroxidation with a 94%, 130% and 96% elevation in lipoprotein malondialdehyde, peroxides and conjugated dienes, respectively, compared with the control LDL. The susceptibility of the patients' LDL to lipid peroxidation decreased by 32% and 44% (measured as malondialdehyde) after 3 weeks of therapy with the angiotensin converting enzyme inhibitors captopril and enalapril, respectively, with no parallel reduction in the patients' blood pressure. The patients' LDL was shown to contain increased content of lipid peroxides and unsaturated fatty acids, which may explain its increased susceptibility to lipid peroxidation. In vitro experiments revealed that LDL can bind angiotensin II, and that angiotensin II has a stimulatory effect on copper-mediated oxidation of LDL, as well as on LDL degradation by macrophages. These results were secondary to cell-mediated oxidation of the LDL and to its cellular uptake via the scavenger receptor. We conclude that LDL derived from patients with essential hypertension is more susceptible to lipid peroxidation than control LDL, and this may be secondary to angiotensin II stimulation of LDL lipid peroxidation in these patients. Furthermore, this LDL demonstrates enhanced cellular uptake by macrophages in comparison with normal LDL which can also be related to angiotensin II-mediated LDL oxidation. Both these phenomena have been shown to be associated with accelerated atherosclerosis, and thus suggest a new mechanism for increased atherogenecity in hypertensive patients.
引用
收藏
页码:71 / 84
页数:14
相关论文
共 63 条
[11]  
AVIRAM M, 1959, ANN NUTR METAB, V30, P143
[12]   DIRECT SCAVENGING OF FREE-RADICALS BY CAPTOPRIL, AN ANGIOTENSIN CONVERTING ENZYME-INHIBITOR [J].
BAGCHI, D ;
PRASAD, R ;
DAS, DK .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1989, 158 (01) :52-57
[13]  
BAIN SC, 1991, J HUM HYPERTENS, V5, P511
[14]  
BARTLETT GR, 1959, J BIOL CHEM, V234, P466
[15]   USE OF THE BETA-CAROTENE RICH ALGA DUNALIELLA-BARDAWIL AS A SOURCE OF RETINOL [J].
BENAMOTZ, A ;
EDELSTEIN, S ;
AVRON, M .
BRITISH POULTRY SCIENCE, 1986, 27 (04) :613-619
[16]   MINIMALLY MODIFIED LOW-DENSITY-LIPOPROTEIN STIMULATES MONOCYTE ENDOTHELIAL INTERACTIONS [J].
BERLINER, JA ;
TERRITO, MC ;
SEVANIAN, A ;
RAMIN, S ;
KIM, JA ;
BAMSHAD, B ;
ESTERSON, M ;
FOGELMAN, AM .
JOURNAL OF CLINICAL INVESTIGATION, 1990, 85 (04) :1260-1266
[17]   METABOLISM OF VERY LOW-DENSITY LIPOPROTEIN PROTEINS .1. PRELIMINARY IN-VITRO AND IN-VIVO OBSERVATIONS [J].
BILHEIMER, DW ;
LEVY, RI ;
EISENBERG, S .
BIOCHIMICA ET BIOPHYSICA ACTA, 1972, 260 (02) :212-+
[18]   CONVERTING ENZYME-INHIBITION WITH AN ORALLY ACTIVE COMPOUND IN HYPERTENSIVE MAN [J].
BRAVO, EL ;
TARAZI, RC .
HYPERTENSION, 1979, 1 (01) :39-46
[19]  
Buege J A, 1978, Methods Enzymol, V52, P302
[20]   MEASUREMENT OF ANGIOTENSIN-II IN BLOOD BY RADIOIMMUNOASSAY [J].
CAIN, MD ;
CATT, KJ ;
COGHLAN, JP .
CLINICA CHIMICA ACTA, 1972, 39 (01) :21-+