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

In patients with essential hypertension, the increased risk for athero sclerosis is related not only to the blood pressure levels per se, but also to other, unknown, factors. Recent observations have indicated t hat oxidation of low density lipoprotein (LDL) and macrophage uptake o f oxidized LDL are implicated in human atherosclerosis. We tested both the susceptibility of LDL, derived from hypertensive patients, to lip id peroxidation as well as its uptake by. macrophages, in comparison w ith control LDL obtained from healthy subjects. The LDL that was deriv ed from 25 patients with essential hypertension demonstrated increased propensity for lipid peroxidation with a 63%, 91% and 69% elevation i n the content of the lipoprotein malondialdehyde, peroxides and conjug ated dienes, respectively, in comparison with control LDL. Minimally m odified LDL (MM-LDL) (prepared by 6 months' storage of the LDL at 4 de grees C) derived from the hypertensive patients also demonstrated incr eased lipid peroxidation with a 94%, 130% and 96% elevation in lipopro tein malondialdehyde, peroxides and conjugated dienes, respectively, c ompared with the control LDL. The susceptibility of the patients' LDL to lipid peroxidation decreased by 32% and 44% (measured as malondiald ehyde) after 3 weeks of therapy with the angiotensin converting enzyme inhibitors captopril and enalapril, respectively, with no parallel re duction in the patients' blood pressure. The patients' LDL was shown t o contain increased content of lipid peroxides and unsaturated fatty a cids, which may explain its increased susceptibility to lipid peroxida tion. In vitro experiments revealed that LDL can bind angiotensin II, and that angiotensin II has a stimulatory effect on copper-mediated ox idation of LDL, as well as on LDL degradation by macrophages. These re sults were secondary to cell-mediated oxidation of the LDL and to its cellular uptake via the scavenger receptor. We conclude that LDL deriv ed from patients with essential hypertension is more susceptible to li pid peroxidation than control LDL, and this may be secondary to angiot ensin II stimulation of LDL lipid peroxidation in these patients. Furt hermore, this LDL demonstrates enhanced cellular uptake by macrophages in comparison with normal LDL which can also be related to angiotensi n II-mediated LDL oxidation. Both these phenomena have been shown to b e associated with accelerated atherosclerosis, and thus suggest a new mechanism for increased atherogenecity in hypertensive patients.