Low density lipoprotein is protected from oxidation and the progression of atherosclerosis is slowed in cholesterol-fed rabbits by the antioxidant N,N''-diphenyl-phenylenediamine.

The oxidative modification of low density lipoprotein (LDL) may play an important role in atherosclerosis. We found that the antioxidant N,N'-diphenyl-1,4-phenylenediamine (DPPD) inhibits in vitro LDL oxidation at concentrations much lower than other reported antioxidants. To test whether DPPD could prevent atherosclerosis, New Zealand White rabbits were fed either a diet containing 0.5% cholesterol and 10% corn oil (control group) or the same diet also containing 1% DPPD (DPPD-fed group) for 10 wk. Plasma total cholesterol levels were not different between the two groups, but DPPD feeding increased the levels of triglyceride (73%, P = 0.007) and HDL cholesterol (26%, P = 0.045). Lipoproteins from DPPD-fed rabbits contained DPPD and were much more resistant to oxidation than control lipoproteins. After 10 wk, the DPPD-fed animals had less severe atherosclerosis than did the control animals: thoracic aorta lesion area was decreased by 71% (P = 0.0007), and aortic cholesterol content was decreased by 51% (P = 0.007). Although DPPD cannot be given to humans because it is a mutagen, our results indicate that orally active antioxidants can have antiatherosclerotic activity. This strongly supports the theory that oxidized LDL plays an important role in the pathogenesis of atherosclerosis.     

Soccer players under regular training show oxidative stress but an improved plasma antioxidant status

Physical activity is known to induce oxidative stress in individuals subjected to intense exercise. In this study, we investigated the lipoprotein profile and the plasma antioxidant status in a group of soccer players engaged in a regular training programme. As was expected for aerobic exercise, high-density lipoprotein-cholesterol (HDL-C) and HDL3-C levels were significantly increased in the sportsmen (P<0.05). Total plasma antioxidant capacity was 25% higher in sportsmen than in controls (P<0.005). Accordingly, plasma hydrosoluble antioxidant levels (ascorbic acid and uric acid) were found to be significantly elevated in the soccer players (P<0.005). In addition, these subjects showed high concentrations of alpha-tocopherol in plasma compared with controls (P<0.005). Furthermore, an increase in plasma superoxide dismutase activity was also observed in relation to exercise (P<0.01). The elevation in plasma activities of antioxidant enzymes and the higher levels of free radical scavengers of low molecular mass may compensate the oxidative stress caused by physical activity. High levels of high-density lipoprotein in plasma may offer additional protection by inhibiting low-density lipoprotein oxidation and thus liposoluble antioxidant consumption. Therefore, soccer players under regular training show an improved plasma antioxidant status in comparison to sedentary controls.     

Paraoxonase and platelet-activating factor acetylhydrolase activities in lipoproteins of beta-thalassemia/hemoglobin E patients.

BACKGROUND: Iron-induced oxidative stress may be implicated in the alteration of the lipoprotein-associated antioxidant enzymes paraoxonase 1 (PON1) and platelet-activating factor acetylhydrolase (PAF-AH), leading to atherosclerosis-related vascular complication in patients with beta-thalassemia hemoglobin E (beta-thal/Hb E). METHODS: Plasma and lipoprotein enzyme activities of PON1 and PAF-AH were studied in 13 mild to moderate and 15 severe cases of beta-thal/Hb E in comparison with 15 normal subjects. RESULTS: PON1 activity was significantly reduced in association with oxidative stress in the patients. There were significant correlations between high-density lipoprotein (HDL)-PON1 activity and oxidative stress markers, including plasma levels of alpha-tocopherol (r=0.694 p<0.001) and the ratio of cholesteryl linoleate to cholesteryl oleate (CL/CO, r=0.662, p<0.001) in HDL. On the other hand, PAF-AH activity was markedly increased in patients by approximately two-fold and three- to four-fold in plasma and lipoproteins, respectively. Significant correlations of low-density lipoprotein (LDL) and HDL-PAF-AH activity with plasma iron, alpha-tocopherol and the CL/CO ratio were also demonstrated. CONCLUSIONS: We suggest that impairment of PON1 activity may be directly caused by oxidative damage, while increased PAF-AH activity possibly results from oxidative stress-induced inflammatory response in beta-thal/Hb E patients.     

心肌梗死患者血清脂蛋白氧化易感性及高密度脂蛋白氧化抑制能力分析

目的 了解心肌梗死存活患者（MIS）血清脂蛋白氧化易感性以及高密度脂蛋白（HDL）对低密度脂蛋白（LDL）氧化抑制能力的变化。方法 采用密度梯度超了心分离33例MIS患者的血清脂蛋白组分（VLDL，LDL，HDL），用A234nm光吸收鉴定脂蛋白氧化易感性，硫代巴比妥酸值（TBARS）分析脂蛋白脂质过氧化程度，并与正常人（44例）进行了比较，结果 MIS患者VLDL、LDL组分脂质过氧化程度明显高于正常人（P＜0.01），氧化延滞时间明显缩短（P＜0.001），HDL组分对LDL氧化抑制能力显著降低（P＜0.01）。结论 MIS患者VLDL，LDL组分氧化易感怀增加，HDL抗氧化能力受损，可能与其动脉粥样硬化的发生发展有关。     

Serum paraoxonase activity in patients with type 1 diabetes compared to healthy controls

BACKGROUND: The oxidation of low-density lipoprotein (LDL) is central to current theories on the initiation and progression of atherosclerosis. Type 1 diabetes is associated with an increase in oxidative stress, which may be responsible for the increased susceptibility to coronary heart disease seen in type 1 diabetes. High-density lipoprotein (HDL) associated paraoxonase (PON1) can retard the oxidation of LDL. DESIGN: Paraoxonase activity, concentration and genotype were therefore investigated in 152 people with type 1 diabetes and 282 healthy controls. These parameters were also investigated in the group with type 1 diabetes in relation to the presence of diabetic complications. RESULTS: Both PON1 activity and concentration were significantly lower by 16.7% and 19.2% (both P < 0.05) in the type 1 diabetes group. These differences were independent of the PON1 coding region polymorphisms. The distribution of PON1 activity and mass were the same in both populations, i.e. for the PON1-192 polymorphism RR > RQ > QQ and for the PON1-55 polymorphism LL > LM > MM. There were no differences in either the PON1 polymorphisms, PON1 activity and concentration in people with type 1 diabetes in the presence or absence of micro and macro vascular complications of diabetes. CONCLUSIONS: Low PON1 activity may contribute to the increased atherosclerosis found in type 1 diabetes by reducing the ability of HDL to retard LDL oxidation despite the frequently-found increased HDL in type 1 diabetes when good glycaemic control is established.     

Effect of Soybean Hypocotyl Extract on Lipid Peroxidation in GK Rats

Vascular complications, as a consequence of atherosclerosis, are main causes of morbidity and mortality in patients with diabetes mellitus. There is increasing evidence that lipid peroxidation and oxidative modification of low density lipoprotein (LDL) is important in atherogenesis. In this study we investigated the effect of soybean hypocotyl extract (SHE), rich in isoflavones and saponins, on lipid peroxide (LPO) levels in liver, plasma and lipoproteins in GK diabetic rats, and its efficacy on the reduction of susceptibility of LDL and high density lipoprotein (HDL) to oxidation. The oxidative modification of LDL and HDL was determined with the lag time of copper ion-induced oxidation curve identified by the conjugated dienes. In SHE group which were fed diet containing 40 g/kg of SHE for 16 weeks, LPO levels in liver, plasma and HDL fraction were significantly decreased compared with the control group. The lag phage of LDL oxidation curve was prolonged noticeably by a mean of 27 min in SHE group as compared to the control group, indicating a reduced susceptibility to oxidation. The results suggest that intake of soybean hypocotyl extract might be useful for the prevention and treatment of diabetes mellitus and diabetes-associated diseases.     

Role of ascorbic acid on in vitro oxidation of low-density lipoprotein derived from hypercholesterolemic patients

BACKGROUND: The susceptibility of low-density lipoprotein (LDL) to oxidation is thought to be a crucial factor responsible for atherogenesis. There is substantial evidence for a role of dietary antioxidants in the prevention of atherogenesis and the protective effect of antioxidant nutrients may be mediated through inhibition of the oxidative modification of LDL. METHODS: We performed in vitro oxidation of LDL derived from normal and hypercholesterolemic individuals in absence and presence of different doses of ascorbic acid. RESULTS: The serum lipid peroxidation level was significantly increased in hypercholesterolemic patients and their LDL has shown a greater propensity towards in vitro oxidation. Hypercholesterolemic LDL required a higher amount of ascorbic acid to reduce its oxidation level as compared to LDL isolated from normocholesterolemic individuals. CONCLUSION: This observation may be of importance in designing future studies of antioxidant supplementation in patients with hypercholesterolemia which is one of the major risk factors for atherosclerosis.     

Reverse cholesterol transport and cholesterol efflux in atherosclerosis

Reverse cholesterol transport (RCT) is a pathway by which accumulated cholesterol is transported from the vessel wall to the liver for excretion, thus preventing atherosclerosis. Major constituents of RCT include acceptors such as high-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I), and enzymes such as lecithin:cholesterol acyltransferase (LCAT), phospholipid transfer protein (PLTP), hepatic lipase (HL) and cholesterol ester transfer protein (CETP). A critical part of RCT is cholesterol efflux, in which accumulated cholesterol is removed from macrophages in the subintima of the vessel wall by ATP-binding membrane cassette transporter A1 (ABCA1) or by other mechanisms, including passive diffusion, scavenger receptor B1 (SR-B1), caveolins and sterol 27-hydroxylase, and collected by HDL and apoA-I. Esterified cholesterol in the HDL is then delivered to the liver for excretion. In patients with mutated ABCA1 genes, RCT and cholesterol efflux are impaired and atherosclerosis is increased. In studies with transgenic mice, disruption of ABCA1 genes can induce atherosclerosis. Levels of HDL are inversely correlated with incidences of cardiovascular disease. Supplementation with HDL or apoA-I can reverse atherosclerosis by accelerating RCT and cholesterol efflux. On the other hand, pro-inflammatory factors such as interferon-gamma (IFN-gamma), endotoxin, tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta), can be atherogenic by impairing RCT and cholesterol efflux, according to in vitro studies. RCT and cholesterol efflux play a major role in anti-atherogenesis, and modification of these processes may provide new therapeutic approaches to cardiovascular disease. Further research on new modifying factors for RCT and cholesterol efflux is warranted.     

Effect of gemfibrozil on the composition and oxidation properties of very-low-density lipoprotein and high-density lipoprotein in patients with hypertriglyceridemia

Recent studies suggest that both oxidized very-low-density lipoprotein (VLDL) and oxidized high-density lipoprotein (HDL) may play a role in the pathogenesis of atherosclerosis. Gemfibrozil is widely used and is reported to decrease VLDL levels and increase HDL levels. The aim of this study was to investigate the effect of gemfibrozil on the chemical composition and oxidative susceptibility of VLDL and HDL and their relationship with atherosclerosis. Twenty patients with hypertriglyceridemia were treated with 300 mg gemfibrozil, 3 times daily, for 12 weeks. Venous blood samples were collected before treatment, at the end of treatment, and 4 weeks after the end of treatment. Gemfibrozil effectively lowered concentrations of plasma lipid, apolipoprotein (apo) B, and apo E. The lipid and protein content of VLDL were also decreased, but not by the same extent. The surface-to-core ratio and apo E/apo B ratio of VLDL particles were increased after gemfibrozil treatment. HDL(2) cholesteryl ester and HDL(3) apo A-II content were also increased. Gemfibrozil treatment lowered levels of lipid peroxides in both VLDL and HDL particles. The susceptibility of VLDL to oxidation was unchanged, whereas maximal peroxide production was decreased. The oxidative susceptibility of both HDL(2) and HDL(3) decreased with gemfibrozil treatment. These results indicate that after gemfibrozil treatment, VLDL and HDL particles in patients with hypertriglyceridemia are less atherogenic, which may explain why gemfibrozil treatment is beneficial in terms of coronary heart disease in hypertriglyceridemia.     

The effect of acetaminophen on oxidative modification of low-density lipoproteins in hypercholesterolemic rabbits

Oxidative modification of low-density lipoproteins (LDL) contributes to the pathology of atherosclerosis. Antioxidants may protect LDL against oxidative modification. Acetaminophen, a widely used analgesic and antipyretic agent, has significant antioxidant properties. However, there is little evidence to suggest that acetaminophen acts as an antioxidant for LDL oxidation in vivo. In this study, we investigated the in vivo effect of acetaminophen on LDL oxidation in hypercholesterolemic rabbits. The oxidative modification of LDL was identified by conjugated dienes and thiobarbituric acid-reactive substances (TBARS). In the cholesterol group which rabbits were fed a diet contained 1% g cholesterol for 8 weeks, TBARS contents and conjugated diene levels in the plasma and isolated LDL samples significantly increased compared with the control rabbits (p<0.05). However, in the cholesterol + acetaminophen group, the TBARS contents and conjugated diene levels were significantly lower than that of the cholesterol group (p<0.05). The results from in vitro studies also demonstrated that the LDL isolated from serum was oxidized by Cu(++) ions and this oxidation reduced in the presence of acetaminophen. The reduced oxidative modification of LDL by acetaminophen may be of therapeutic value in preventing the development and progression of atherosclerosis.     

Gemfibrozil treatment potentiates oxidative resistance of high-density lipoprotein in hypertriglyceridemic patients

BACKGROUND: Studies suggest that both oxidized low and high density lipoprotein (LDL and HDL) play a role in the pathogenesis of atherosclerosis. Gemfibrozil is widely used and is reported to increase cholesterol of LDL and HDL in hypertriglyceridemic patients. The aim of this study was to investigate the effect of gemfibrozil treatment on the oxidative status of lipoprotein particles in Fredrickson phenotype IV hypertriglyceridemic patients. METHODS: Twenty-two patients, aged 38-64 years, with fasting plasma triglyceride concentrations between 2.90 and 8.97 mmol L(-1), were recruited and were given gemfibrozil 300 mg three times daily for 12 weeks. Venous blood samples were collected before gemfibrozil treatment, after 4, 8, or 12 weeks of treatment, and 4 weeks after termination of treatment, and used to analyse the plasma lipid profile, isolate lipoproteins, and analyse the chemical composition and in vitro oxidation of lipoprotein particles. RESULTS: Gemfibrozil treatment resulted in a decrease in plasma total triglyceride levels and the triglyceride content of all lipoproteins. Plasma total cholesterol levels were decreased as a result of a decrease in very low density lipoprotein (VLDL) cholesterol levels. A slight increase in LDL cholesterol levels was observed, whereas the thiobarbituric acid-reactive substances (TBARS) of LDL were decreased and the lag and peak time of LDL to oxidation were unchanged and maximal diene production was decreased. Plasma HDL cholesterol levels, the surface-to-core ratio of HDL particles, and the resistance of HDL to oxidation were increased. CONCLUSION: The decreased TBARS and diene production of LDL, increased HDL cholesterol levels, and increased resistance of HDL to oxidation may, in part, explain why gemfibrozil treatment was found to be generally beneficial in terms of protection against coronary heart disease.     

Association of oxidative stress and PON1 with LDL and HDL particle size in middle-aged subjects

BACKGROUND: Alterations in plasma lipoprotein subclass distributions affect atherosclerosis risk. Smaller, denser low-density lipoprotein (LDL) particles (sdLDL) are more susceptible to oxidation. In contrast, most of the protective effects of high-density lipoproteins (HDL) are attributable to larger particles. This study investigates the connection between LDL and HDL particle heterogeneity and oxidative stress, antioxidative defence (AOD) and paraoxonase (PON1) status in a healthy middle-aged Serbian population. MATERIALS AND METHODS: LDL and HDL particle sizes and subclass distributions were measured by gradient gel electrophoresis in 104 men and 103 women, aged 53 +/- 9.4 years. PON1 activities and PON1(Q192R) phenotypes were determined with paraoxon and diazoxon as substrates. The oxidative stress/AOD status was estimated by measuring malondialdehyde (MDA) and superoxide-anion (O2*(-)) levels and superoxide-dismutase (SOD) activity. RESULTS: Subjects with sdLDL had significantly higher MDA (P < 0.001) and O2*(-)(P < 0.05) levels and greater diazoxonase (DZOase) activity (P < 0.05) compared to subjects with larger LDL particles. A high MDA concentration was a significant predictor of the sdLDL phenotype (P < 0.005). Increased levels of and MDA were associated with smaller HDL(3) subclass abundance. Reduced HDL particle size was associated with lower DZOase activity (P < 0.01). CONCLUSIONS: Even in the absence of symptoms of atherosclerosis, sdLDL particles are associated with increased oxidative stress, which may stimulate a compensatory rise in PON1 DZOase activity. Elevated oxidative stress may significantly affect HDL subclass distribution, resulting in the accumulation of smaller, denser HDL particles with diminished antioxidative capacity.     

New insights on oxidative stress in the artery wall

Atherosclerosis and its resultant cardiovascular events represent a state of heightened oxidative stress that is commonly thought to contribute to atherogenesis. The aim of this review is to summarize the data linking oxidative events to the pathogenesis of atherosclerosis. Despite abundant data supporting the presence of lipid and protein oxidation in the vascular wall, the poor performance of antioxidant strategies in limiting either atherosclerosis or cardiovascular events from atherosclerosis remain a fundamental problem for implicating oxidative stress as pathophysiologically important. Direct evidence that oxidative stress in general, and the oxidative modification of low-density lipoprotein in particular, is both necessary and sufficient for atherosclerosis has been difficult to find. There are many potential reasons for this difficulty, not the least of which is our lack of sufficient knowledge delineating the precise molecular events that beget oxidative stress in the vessel wall, and the precise mediators involved. Further investigation elucidating these oxidative events are required to provide us with the tools to limit oxidative stress at its source and ameliorate all of its secondary phenomena. Only then will we know what components of atherosclerosis are directly due to oxidative stress.     

Atherogenic risk factors in cerebrotendinous xanthomatosis

In a study of coronary artery disease in patients with cerebrotendinous xanthomatosis (CTX), we documented the presence or absence of atherogenic risk factors and performed detailed analyses of serum lipid and lipoprotein profiles. Four of the seven patients examined had coronary arterial narrowing and/or obstruction, but multiple atherogenic risk factors were not found in any of these patients. Total cholesterol (T.ch) levels and low density lipoprotein-cholesterol (LDL-ch) levels were lower, and high density lipoprotein2-cholesterol (HDL2-ch) levels were higher in CTX patients than in controls. Triglyceride and very low density lipoprotein (VLDL) levels were significantly lower in the former. Indices correlating with the risk of atherosclerosis, such as the atherogenic index, and the ratios of apolipoprotein B/apolipoprotein AI, HDL2-ch/LDL-ch, HDL2-ch/HDL3-ch, indicated that CTX serum was, in fact, 'anti-atherogenic'. However, coronary artery disease is frequently seen in patients with CTX. This discrepancy suggests the existence of a unique mechanism by which atherosclerosis is induced in patients with CTX. We discuss a mechanism of disturbed lipoprotein metabolism which might be responsible for the deposition of sterols in the tissues of patients with CTX.     

Current understanding of the role of high-density lipoproteins in atherosclerosis and senescence

Numerous epidemiologic and interventional studies revealed that high-density lipoprotein (HDL) is an important risk factor for coronary heart disease. There are several well documented HDL functions that may account for the antiatherogenic effects of this lipoprotein. The best recognized of these is the capacity of HDL to transport cholesterol from the periphery to the liver, and thereby prevent cholesterol deposition in the arterial wall. Further properties of HDL that may also be antiatherogenic include its potent anti oxidative and anti-inflammatory action. In addition, HDL seems to be involved in processes related to senescence at both the cellular and whole-organism level. Both protein components of HDL (such as apolipoprotein A-I) and its lipid components (such as, lysosphingolipids) appear to mediate the antiatherogenic and anti-aging effects of HDL. The purpose of this review is to summarize the novel functions of HDL that may protect from atherosclerosis and senescence.     

Alterations of paraoxonase and platelet-activating factor acetylhydrolase activities in patients on peritoneal dialysis.

OBJECTIVE: The more atherogenic lipid profile seen in peritoneal dialysis (PD) patients cannot fully explain the increased incidence of atherosclerosis in this population. Oxidative modification of low-density lipoproteins (LDL) is considered to play a central role in the atherogenic process, whereas high-density lipoprotein (HDL) protects LDL from oxidation. On the other hand, it has been suggested that the LDL and HDL of PD patients are more resistant to oxidation than those of control subjects, while PD-HDL equally protects LDL from oxidation compared to control-HDL. Two HDL-associated enzymes have been shown to protect both LDL and HDL from oxidation: paraoxonase (PON1) and HDL-associated platelet-activating factor acetylhydrolase (HDL-PAF-AH). Furthermore, low PON1 activity and high total plasma PAF-AH concentration, which represents mainly the LDL-associated enzyme, have been shown to be independent risk factors for coronary artery events in the general population. However, there are limited data regarding possible alterations of these enzymes in PD patients. The aim of our study was to examine the possible alterations of PON1 and PAF-AH activities in patients undergoing PD. DESIGN: A cross-sectional study. SETTING: A university medical center. PARTICIPANTS: 56 PD patients of Caucasian origin and 86 matched controls were studied. MEASUREMENTS: In all subjects, serum PON1 activity toward paraoxon (paraoxonase) and phenylacetate (arylesterase), as well as total serum and HDL-PAF-AH activities were measured; PON1 genetic polymorphisms known to influence PON1 activity (Q192R and M55L) were determined. RESULTS: The PD patients exhibited significantly increased serum PON1 (paraoxonase) and PON1 (arylesterase) activities compared to controls, regardless of the PON1 polymorphisms or the levels of HDL cholesterol. Additionally, PD patients had significantly elevated activities of total serum PAF-AH and HDL-PAF-AH, independently of the levels of LDL or HDL cholesterol. The ratio of HDL-PAF-AH/ total PAF-AH, which has recently been suggested to be a potential marker of atherogenicity, was decreased in these patients compared to controls. Moreover, no difference in the prevalence of PON1 polymorphisms between PD patients and controls was found. CONCLUSION: The elevated activities of PON1 and HDL-PAF-AH could explain the increased resistance of PD-HDL to oxidation; the higher activity of total PAF-AH and the decreased HDL-PAF-AH/ total PAF-AH ratio could contribute to the increased incidence of atherosclerosis in these patients.     

Prevention of Hypercholesterolemic Atherosclerosis by Garlic, an Antixoidant

BACKGROUND: Investigations of the effects of high cholesterol diet in the presence and absence of garlic on the genesis of atherosclerosis, the blood lipid profile, aortic tissue lipid peroxidation product malondialdehyde, chemiluminescence, a marker for antioxidant reserve and activity of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase were made in rabbits. METHODS AND RESULTS: Four groups of 10 rabbits each were studied: group 1 was given regular rabbit chow, group 2 was given rabbit chow diet supplemented with garlic powder (300 mg twice daily orally), group 3 was given 1% cholesterol diet, group 4 was given 1% cholesterol diet supplemented with garlic powder (300 mg twice daily orally). Blood concentration of triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol were measured before and after 4 and 10 weeks of experimental diets. The aorta was removed at the end of protocol (10 weeks) for assessment of atherosclerotic changes (gross and microscopic), malondialdehyde concentration, chemiluminescence, and activity of antioxidant enzymes. Total cholesterol, low density-lipoprotein cholesterol and ratio of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol and ratio of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol increaserd in group 3 and 4; the increase was smaller in group 4 than in in group 3 although not significant. Serum high-density lipoprotein cholesterol decreased to a similar extent in groups 3 and 4. Serum triglyceride and very low-density lipoprotein cholesterol remained unchanged in group 3 but increased in group 4. These values were significantly higher than those in group 1. Garlic in rabbits with control diet decreased the levels of triglyceride and very low density lipoprotein but did not affect the levels of total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol and the ratio of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol. There was an increase in aortic tissue malondialdehyde, chemiluminescence, and activities of catalase and glutathione peroxidase in group 3 compared with those in group 1. Levels of aortic malondialdehyde, chemiluminescence, catalase, and glutathione peroxidase were lower in group 4 compared with group 3; however, values for malondialdehyde and chemiluminescence were lower and that of catalase and glutathione peroxidase were higher in group 4 compared with group 1. Superoxide dismutase activity was similar in all the four groups. Malondialdehyde, chemiluminescence, and activity of catalase of aortic tissue decreased while activity of glutathione peroxidase increased in group 2. Atherosclerotic changes were lower in group 4 compared with group 3. Histologic changes were practically similar in groups 3 and 4. CONCLUSIONS: Increased levels of malondialdehyde, chemiluminescence, and antioxidant enzymes associated with development of atherosclerosis suggests a role for oxygen free radicals in the pathogenesis of hypercholesterolemic atherosclerosis. The protection afforded by garlic was associated with decrease in aortic malondialdehyde and chemiluminescence inspite of no change in serum cholesterol. These findings suggest that oxygen free radicals are involved in the genesis and maintenance of hypercholesterolemic atherosclerosis and that use of garlic can be useful in preventing the development of hypercholesterolemic atherosclerosis.     

Current understanding of the role of high-density lipoproteins in atherosclerosis and senescence

Numerous epidemiologic and interventional studies revealed that high-density lipoprotein (HDL) is an important risk factor for coronary heart disease. There are several well documented HDL functions that may account for the antiatherogenic effects of this lipoprotein. The best recognized of these is the capacity of HDL to transport cholesterol from the periphery to the liver, and thereby prevent cholesterol deposition in the arterial wall. Further properties of HDL that may also be antiatherogenic include its potent anti oxidative and anti-inflammatory action. In addition, HDL seems to be involved in processes related to senescence at both the cellular and whole-organism level. Both protein components of HDL (such as apolipoprotein A-I) and its lipid components (such as, lysosphingolipids) appear to mediate the antiatherogenic and anti-aging effects of HDL. The purpose of this review is to summarize the novel functions of HDL that may protect from atherosclerosis and senescence.     

The effect of hormone replacement therapy on oxidized low density lipoprotein levels and paraoxonase activity in postmenopausal women

Oxidized low-density lipoproteins (oxLDL) are involved in initiation of atherosclerosis. Paraoxonase 1 (PON1), the isoenzyme of PON, is located on high-density lipoprotein (HDL) and protects against the oxidative modification of both HDL and LDL by hydrolysing lipid peroxides. Postmenopausal women have a higher risk of cardiovascular events compared with premenopausal women. The aim of this clinical study was to evaluate the effects of hormone replacement therapy (HRT) on oxLDL and PON1 activity in menopausal status. The subjects included 45 healthy postmenopausal women, aged 43 to 57 years, and 30 premenopausal women with regular cycles, aged 31 to 40 years. None of the participating women had a history of hypertension, diabetes mellitus or medications known to affect the cardiovascular system. Twenty five of the postmenopausal women received conjugated estrogens at dose of 0.625 mg/day per oral (P.O.) and medroxyprogesterone acetate (MPA) (1 mg/d P.O.) for 10 days. Twenty of the postmenopausal women received 17-beta estradiol (2 mg/day) and norethysterone acetate (NETA) (5 mg/day P.O.) for 10 days. Fasting blood samples were taken from premenopausal women (baseline) and postmenopausal women after HRT of 6 months to determine serum malondialdehyde (MDA), oxLDL, and PON1 activity. After 6-month therapy, MDA and oxLDL levels showed a statistically significant reduction in the treated groups versus baseline (p <0.05), whereas PON1 activities were increased (p <0.05). Increase in oxidative status may be one of the factors leading to reduction in PON1 activity and increased oxLDL in menopause. HRT may be effective on oxidative stress and lipoprotein metabolism in apparently healthy postmenopausal women.     

Effect of acetaminophen on atherosclerosis.

OBJECTIVE: To evaluate the antioxidant effects of acetaminophen in atherosclerosis. DATA SOURCES: Experimental literature and abstracts accessed through MEDLINE (1966-February 2001). DATA SYNTHESIS: Atherosclerosis is an inflammatory disorder associated with coronary events. The oxidative stress burden resulting from excess pro-oxidant free radical formation contributes to oxidative modification of low-density lipoprotein (lipid peroxidation) and is associated with atherosclerosis. Acetaminophen (phenol-like compound) may limit these key processes that are involved. The findings of earlier experimental laboratory tests and abstracts are evaluated. CONCLUSIONS: In vitro data suggest that acetaminophen may reduce lipid peroxidation, whereas animal data showed decreased progression of atherosclerosis. Further animal model and human studies are required to confirm these earlier findings.