200
S-5-5
Lipid
Peroxidation,Vitamin J.MUSIAL,
Department of 31-066 Cracow,
Medicine, Poland
E,and
Cardiovascular
T. B. DOMAGALA,
Copernicus
Academy
and
of
Disease
A. SZCZEKLIK
Medicine,
Skawinska
8,
I.
INTRODUCTION As early as in 1978 Nord$y et al. [1] discovered that human low density proteins (LDL) inhibit the generation of an unstable anti-aggregatory principle by cultured human endothelial cells. A year later Henriksen et al. [2] described that a damage to cultured endothelial cells by LDL did not occur either in presence of high density lipoproteins (HDL) or when a modification of the procedure for preparation of LDL was introduced. This modification consisted of the introduction of an antioxidant, butylated hydroxytoluene (BHT), at all stages of the adopted preparative procedure for LDL [1]. We confirmed that BHT reduced a thiobarbituric acid-reactive substance (TBARS) in LDL from 9 to below 1 nmoles/mg LDL. Moreover, we demonstrated that BHT-treated LDL did not inhibit the generation of prostacyclin (PGI2) by rat aortic slices, whereas oxidized LDL were powerful inhibitors of PGI2 formation by arterial wall [3,4]. We also found that bovine coronary arterial strip pretreated with oxidized LDL hardly transformed arachidonic acid to PGI2. These findings prompted us to put forward a hypothesis that LDL are carriers for lipid peroxides [3] and thus inhibit PGI2 synthase in arterial endothelial cells [5]. Thus, in vitro experiments pointed to a difference between native and oxidized LDL (n-LDL and ox-LDL) in their actions on biosynthesis of PGI2 by arterial walls. Unlike n-LDL, ox-LDL inhibited release of PGI2 from arteries. There is also growing evidence that ox-LDL might inhibit the generation of another vasodilatory product of endothelium, namely "endothelium-derived relaxing factor" (EDRF) [6, 7].
II.
LIPID PEROXIDES, PGI2, AND THE EFFECT OF VITAMIN E The effect of lipid peroxides on the production of prostacyclin in vivo has been studied in an experimental model. Feeding an atherogenic diet to 25 rabbits for a week resulted in elevation of plasma lipid peroxides (as measured by thiobarbituric acid reactive substances-TBARS-in plasma) and a 90% decrease in arterial generation of prostacyclin. Enrichment of the atherogenic diet with 100mg vitamin E daily prevented the increase in plasma lipid peroxides and protected the prostacyclin generating system in arteries (Table 1). Thus,in hyperlipoproteinemias vitamin E corrects certain abnormalities of lipid metabolism which might predispose to atherosclerosis [8]. Moreover, plasma lipid peroxide levels correlated inversely with arterial capacity to generate PGI2 (r=0.8, p
S-5-5
Lipid
Peroxidation,Vitamin J.MUSIAL,
Department of 31-066 Cracow,
Medicine, Poland
E,and
Cardiovascular
T. B. DOMAGALA,
Copernicus
Academy
and
of
Disease
A. SZCZEKLIK
Medicine,
Skawinska
8,
I.
INTRODUCTION As early as in 1978 Nord$y et al. [1] discovered that human low density proteins (LDL) inhibit the generation of an unstable anti-aggregatory principle by cultured human endothelial cells. A year later Henriksen et al. [2] described that a damage to cultured endothelial cells by LDL did not occur either in presence of high density lipoproteins (HDL) or when a modification of the procedure for preparation of LDL was introduced. This modification consisted of the introduction of an antioxidant, butylated hydroxytoluene (BHT), at all stages of the adopted preparative procedure for LDL [1]. We confirmed that BHT reduced a thiobarbituric acid-reactive substance (TBARS) in LDL from 9 to below 1 nmoles/mg LDL. Moreover, we demonstrated that BHT-treated LDL did not inhibit the generation of prostacyclin (PGI2) by rat aortic slices, whereas oxidized LDL were powerful inhibitors of PGI2 formation by arterial wall [3,4]. We also found that bovine coronary arterial strip pretreated with oxidized LDL hardly transformed arachidonic acid to PGI2. These findings prompted us to put forward a hypothesis that LDL are carriers for lipid peroxides [3] and thus inhibit PGI2 synthase in arterial endothelial cells [5]. Thus, in vitro experiments pointed to a difference between native and oxidized LDL (n-LDL and ox-LDL) in their actions on biosynthesis of PGI2 by arterial walls. Unlike n-LDL, ox-LDL inhibited release of PGI2 from arteries. There is also growing evidence that ox-LDL might inhibit the generation of another vasodilatory product of endothelium, namely "endothelium-derived relaxing factor" (EDRF) [6, 7].
II.
LIPID PEROXIDES, PGI2, AND THE EFFECT OF VITAMIN E The effect of lipid peroxides on the production of prostacyclin in vivo has been studied in an experimental model. Feeding an atherogenic diet to 25 rabbits for a week resulted in elevation of plasma lipid peroxides (as measured by thiobarbituric acid reactive substances-TBARS-in plasma) and a 90% decrease in arterial generation of prostacyclin. Enrichment of the atherogenic diet with 100mg vitamin E daily prevented the increase in plasma lipid peroxides and protected the prostacyclin generating system in arteries (Table 1). Thus,in hyperlipoproteinemias vitamin E corrects certain abnormalities of lipid metabolism which might predispose to atherosclerosis [8]. Moreover, plasma lipid peroxide levels correlated inversely with arterial capacity to generate PGI2 (r=0.8, p
