Why very low density lipoprotein levels are normal in familial hyperchylomicronaemia.

The anomalous finding that very low density lipoprotein levels are relatively normal in patients with familial hyperchylomicronaemia has never been satisfactorily explained, particularly in view of the marked reduction or absence of peripheral lipoprotein lipase activity characteristic of this condition. I propose that the discrepancy between the plasma levels of the two triglyceride-rich lipoprotein fractions in these patients is due to the secretion by the liver of triglyceride in the form of chylomicron-like particles, rather than as very low density lipoprotein. The proposed "switch" in the spectrum of lipoproteins secreted by the liver is probably contingent upon the activity of the hepatic lipase present on the liver cell plasma membrane.     

非高密度脂蛋白胆固醇与冠状动脉病变严重程度的相关性

目的观察冠状动脉粥样硬化性心脏病(CHD)患者非高密度脂蛋白胆固醇与冠状动脉病变严重程度的相关性,及其预测严重冠状动脉狭窄的能力。方法收集843例CHD患者,根据冠状动脉造影结果将患者分为单支、双支、三支病变组,用Gensini积分评估患者冠状动脉病变狭窄严重程度并按积分四分位数分成Q1～Q4组共4组,分别比较各组间血脂参数差异。用Spearman相关系数分析患者低密度脂蛋白胆固醇(LDLC)、非高密度脂蛋白胆固醇(non-HDLC)、总胆固醇/高密度脂蛋白胆固醇(TC/HDLC)、甘油三酯/高密度脂蛋白胆固醇(TG/HDLC)与Gensini积分的关系。采用受试者工作特征曲线(ROC)和多因素Logistic回归评价LDLC、non-HDLC、TC/HDLC、TG/HDLC预测严重冠状动脉狭窄的能力。结果患者LDLC、non-HDLC、TC/HDLC水平随Gensini积分增高显著增加(P均0.05),Q4组TG/HDLC显著高于Q1和Q2组(P均0.05)。LDLC、non-HDLC、TC/HDLC水平随冠状动脉病变支数增加显著增加(P均0.05),TG/HDLC在各组间差异无显著性。non-HDLC与Gensini积分(r=0.315,P0.01)相关性高于LDLC(r=0.252,P0.01)、TC/HDLC(r=0.242,P0.01)、TG/HDLC(r=0.123,P0.01)。non-HDLC预测高Gensini积分的ROC曲线下面积是0.729(95%Cl 0.691～0.767,P0.01),分别大于LDLC的0.694(95%Cl 0.653～0.734,P0.01)、TC/HDLC的0.681(95%Cl 0.640～0.721,P0.01)、TG/HDLC的0.564(95%Cl 0.521～0.607,P0.01)。用多因素Logistic回归校正冠心病危险因素后,non-HDLC(OR=2.472, 95%Cl 1.962～3.115)预测严重冠状动脉病变的能力轻微优于LDLC(OR=2.265, 95%Cl 1.785-2.875)、TC/HDLC(OR=1.796, 95%Cl 1.483～2.175)、TG/HDLC(OR=1.022, 95%Cl 0.927～1.127)。结论 non-HDLC在预测严重冠状动脉病变方面优于LDLC、TC/HDLC、TG/HDLC,有助于对CHD患者的危险分层。     

Ath-1, a gene determining atherosclerosis susceptibility and high density lipoprotein levels in mice.

High density lipoprotein (HDL) is the major plasma lipoprotein found in mice fed normal laboratory chow containing 4% fat. When female mice from some inbred strains, such as C57BL/6, are fed a high fat diet (1.25% cholesterol, 15% fat, and 0.5% cholic acid), the levels of HDL-cholesterol decrease by about 50%, and lipid staining lesions form in the aorta within 14 weeks. In other strains of mice, such as C3H and BALB/c, HDL-lipid levels decrease only slightly, and few or no aortic lesions are observed at 14 weeks. The genetic basis of these phenotypic differences was analyzed by using recombinant inbred strains derived from C57BL/6 and BALB/c and also from C57BL/6 and C3H/He. The two phenotypes segregated as simple Mendelian traits, and no recombination was observed between them. Thus, HDL-cholesterol levels and susceptibility to atherosclerosis appear to be determined by the same gene (or by two closely linked genetic factors that are a maximum of 1.7 centimorgans apart). This gene was named Ath-1, for atherosclerosis susceptibility, with alleles r for resistance and s for susceptibility. Ath-1 maps on chromosome 1 near Alp-2, a gene that determines the structure of apolipoprotein A-II, one of the two major proteins found in HDL. Ath-1 is clearly separable from Alp-2, and the distance between these genes is 6.0 centimorgans with a standard error of 4.2 centimorgans. In humans, levels of HDL are inherited and are inversely correlated with atherosclerosis; familial hyperalphalipoproteinemia is associated with high levels of HDL-cholesterol and decreased risk of heart disease. The human trait phenotypically resembles Ath-1 in the mouse.     

Low high density lipoprotein levels are associated with an elevated blood viscosity.

Low levels of high density lipoprotein (HDL) have been inversely correlated with blood viscosity and plasma viscosity; however, the contribution of concomitant hypertriglyceridemia may confound this association. This study evaluated the relationship between blood viscosity and HDL cholesterol in 70 subjects with fasting levels of total cholesterol <5.2 mmol/l (200 mg/dl) and triglycerides <2.3 mmol/l (200 mg/dl). Viscosity (mPa x s) was measured at 37 degrees C with a coaxial cylinder microviscometer. HDL cholesterol was inversely associated with corrected blood viscosity at 100 s(-1) (beta = -0.49, P<0.00005) and 20 s(-1) (beta = -0.38, P = 0.001) but not at 1 s(-1) (beta = -0.05, P = 0.69) using stepwise multivariate analyses. Low HDL levels are associated with an elevated blood viscosity, and this rheological abnormality may contribute to cardiovascular risk in subjects with isolated low HDL levels.     

Suppression of diet-induced atherosclerosis in low density lipoprotein receptor knockout mice overexpressing lipoprotein lipase.

Lipoprotein lipase (LPL) is a key enzyme in the hydrolysis of triglyceride-rich lipoproteins. Conflicting results have been reported concerning its role in atherogenesis. To determine the effects of the overexpressed LPL on diet-induced atherosclerosis, we have generated low density lipoprotein receptor (LDLR) knockout mice that overexpressed human LPL transgene (LPL/LDLRKO) and compared their plasma lipoproteins and atherosclerosis with those in nonexpressing LDLR-knockout mice (LDLRKO). On a normal chow diet, LPL/LDLRKO mice showed marked suppression of mean plasma triglyceride levels (32 versus 236 mg/dl) and modest decrease in mean cholesterol levels (300 versus 386 mg/dl) as compared with LDLRKO mice. Larger lipoprotein particles of intermediate density lipoprotein (IDL)/LDL were selectively reduced in LPL/LDLRKO mice. On an atherogenic diet, both mice exhibited severe hypercholesterolemia. But, mean plasma cholesterol levels in LPL/ LDLRKO mice were still suppressed as compared with that in LDLRKO mice (1357 versus 2187 mg/dl). Marked reduction in a larger subfraction of IDL/LDL, which conceivably corresponds to remnant lipoproteins, was observed in the LPL/LDLRKO mice. LDLRKO mice developed severe fatty streak lesions in the aortic sinus after feeding with the atherogenic diet for 8 weeks. In contrast, mean lesion area in the LPL/LDLRKO mice was 18-fold smaller than that in LDLRKO mice. We suggest that the altered lipoprotein profile, in particular the reduced level of remnant lipoproteins, is mainly responsible for the protection by LPL against atherosclerosis.     

Associations between serum lipoprotein(a) levels and the severity of coronary and aortic atherosclerosis

To elucidate the associations between Lp(a) levels and coronary and aortic atherosclerosis, we performed aortic MRI in 143 patients undergoing coronary angiography. Severity of aortic atherosclerosis was represented as plaque scores. Of the 143 patients, 104 had coronary artery disease (CAD). Thoracic and abdominal aortic plaques were found in 89 and 131 patients. Lp(a) levels increased stepwise with the number of stenotic coronary vessels: 15.7 (CAD(-)), 21.2 (1-vessel), 21.4 (2-vessel), and 22.9 mg/dl (3-vessel) (P<0.05). For aortic atherosclerosis, 143 patients were divided into quartiles by plaque scores. Lp(a) did not differ among quartiles of thoracic plaques: 17.1, 19.0, 23.5, and 21.2 mg/dl (P=NS), whereas Lp(a) increased stepwise with quartiles of abdominal plaques: 17.1, 19.2, 19.1, and 24.0 mg/dl (P<0.05). Lp(a) was an independent factor for CAD and abdominal aortic plaques, but not thoracic plaques. Thus, Lp(a) levels were associated with aortic atherosclerosis, especially in abdominal aorta, as well as coronary atherosclerosis.     

Influence of hypertension on aortic atherosclerosis in the Watanabe rabbit

The effects of one-kidney, one clip Goldblatt hypertension on aortic atherosclerosis have been studied in the Watanabe heritable hyperlipidemic (WHHL) rabbit. Renovascular surgery was performed on WHHL rabbits at 3 months of age, and the rabbits were followed for periods of 3-6 months. Aortic atherosclerosis was assessed by measurement of intimal surface involvement with atherosclerotic lesions, determination of aortic free and ester cholesterol content, and microscopic examination. Systolic blood pressure increased by approximately 40-60 mm Hg in the renovascular surgical group as compared with the sham-operated group, but body weight, heart rate, serum cholesterol, and serum triglyceride were unaffected. Aortic atherosclerosis was increased in the hypertensive rabbits, even after 2-3 months of hypertension. At 3 months after renovascular surgery, the aortic surface area covered by atherosclerotic disease averaged 77 +/- 4.4% in hypertensive as compared with 16 +/- 3.3 in control rabbits. At 6 months after surgery, the values were 62 +/- 8.2% and 30 +/- 5.3% in the hypertensive and control rabbits, respectively. The differences in surface involvement and cholesterol content as a result of hypertension were particularly prominent in the descending thoracic aorta. Atherosclerotic lesions in the descending thoracic and abdominal aortic regions of normotensive WHHL rabbits were localized primarily to the ostia of branch vessels, but in the hypertensive rabbits, the involvement was typically very diffuse. No major differences in the nature of atherosclerotic lesions of comparable size were apparent by light microscopy. The results indicate that hypertension accelerates atherogenesis in the WHHL rabbit and suggest that this model may be valuable for studying the mechanisms by which such acceleration is induced.     

Triglycerides and triglycerides to high-density lipoprotein cholesterol ratio are strong predictors of incident hypertension in Middle Eastern women

Dyslipidemia has been reported as a risk factor for incident hypertension in a few prospective studies, however, no study has specifically assessed different lipid measures including the lipid ratios, that is, total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs)/HDL-C as predictors of hypertension among Middle Eastern women with high prevalences of dyslipidemia and hypertension. The study population consisted of 2831 non-hypertensive women, aged ≥ 20 years. We measured lipoproteins, and calculated non-HDL-C and the lipid ratios. The risk-factor-adjusted odds ratios for incident hypertension were calculated for every 1 standard deviation (s.d.) change in TC, log-transformed TG, HDL-C, non-HDL-C, TC/HDL-C and log-transformed TG/HDL-C using multivariate logistic regression analysis. Over a mean follow-up of 6.4 years, 397 women developed hypertension. An increase of 1 s.d. in TG, TC/HDL-C and TG/HDL-C increased the risk of incident hypertension by 16, 19 and 18%, respectively, and 1 s.d. increase in HDL-C decreased the risk of hypertension by 14% in the multivariable model (all P ≤ 0.05). In models excluding women with diabetes and central or general obesity, TG, TG/HDL-C and TC/HDL-C remained as independent predictors of incident hypertension. In conclusion, dyslipidemia, using serum TG and TG/HDL-C, in particular, may be useful in identification of women at risk of hypertension, even in those without diabetes and central or general obesity.     

The effects of low density lipoprotein and high density lipoprotein on phosphoinositide hydrolysis in bovine aortic endothelial cells.

Low density lipoprotein (LDL) and high density lipoprotein (HDL3) were tested for their ability to induce inositol phospholipid turnover and inositol phosphate production in bovine aortic endothelial cells (BAEC). The production of inositol phosphates following hydrolysis of the phosphoinositides was demonstrated by two methods; release of [3H]inositol phosphates after labelling with [3H]myo-inositol and by a direct binding assay for inositol 1,4,5-trisphosphate (InsP3). Acute exposure to LDL induced InsP3 release at low concentrations of the lipoprotein within the physiological range of LDL in tissues. HDL3 did not cause any release of the inositol phosphates. Pre-incubation of BAEC with HDL3 suppressed bradykinin- and LDL-induced inositol phosphate production in BAEC in a concentration-dependent manner. It is concluded that LDL acutely stimulates phosphoinositide breakdown and that pre-incubation of cells with HDL3 inhibits this effect. The mechanism responsible for these effects remains to be elucidated.     

Characterisation of the lipoprotein structure in the St. Thomas' Mixed Hyperlipidaemic (SMHL) rabbit

Familial combined hyperlipidaemia (FCHL) is a complex genetic disorder of unknown aetiology. Study of this human condition over many decades has been hampered by likely genetic heterogeneity. In order to find better phenotypic markers, we have characterised the structures of VLDL, IDL and LDL in the St. Thomas' Mixed Hyperlipidaemic (SMHL) rabbit--an animal model of FCHL in which the hyperlipidaemia is caused primarily by an increased production rate of apolipoprotein B (apoB)--containing lipoproteins-and compared them with those in the Watanabe Heritable Hyperlipidaemic (WHHL) rabbit, in which hyperlipidaemia is caused mainly by a defect in lipoprotein clearance, and those in the normolipidaemic New Zealand White (NZW) animal. All three rabbit strains were fed a cholesterol-enriched (0.08%, w/w) diet for at least 3 months prior to blood sampling. Both SMHL and WHHL rabbits showed combined hyperlipidaemia as evidenced by significantly increased levels of plasma cholesterol and triglycerides. Raised plasma lipids in the SMHL rabbit were attributable mainly to an overabundance of lipoprotein particles with the same lipid composition as those in NZW rabbits. VLDL and IDL in the SMHL rabbit showed a significantly increased sphingomyelin to phosphatidyl choline ratio. In the WHHL rabbit there was a high concentration of particles that were significantly enriched in cholesteryl esters and depleted in triglycerides. Phospholipids in all lipoprotein fractions from WHHL rabbits contained significantly more sphingomyelin and less phosphatidyl choline resulting in a significantly increased sphingomyelin to phosphatidyl choline ratio. We found that the VLDL of SMHL rabbits could be distinguished from that of NZW rabbits on the basis of the cholesterol:apoB and the sphingomyelin:phosphatidylcholine ratios, and from that of WHHL rabbits by the sphingomyelin:triglyceride ratio. Extrapolating these findings to the human condition, an assessment of particle core composition, together with the proportion of sphingomyelin in phospholipids especially in VLDL might help in the differentiation of the combined hyperlipidaemia of FCHL into disorders of lipoprotein overproduction versus decreased clearance.     

Defects in the low density lipoprotein receptor gene affect lipoprotein (a) levels: multiplicative interaction of two gene loci associated with premature atherosclerosis.

The lipoprotein (a) [Lp(a)] contains two nonidentical protein species, apolipoprotein (apo) B-100 and a specific high molecular weight glycoprotein, apo(a). Lp(a) represents a continuous quantitative genetic trait, the genetics of which are only poorly understood. Genetic variation at the apo(a) locus affects plasma Lp(a) levels and explains at least 40% of the variability of this trait. Lp(a) levels were found to be elevated 3-fold in the plasma from patients with the heterozygous form of familial hypercholesterolemia who have one mutant low density lipoprotein receptor gene. This elevation was not due to a higher frequency of those apo(a) types that are associated with high Lp(a) levels in familial hypercholesterolemia patients. Rather Lp(a) levels were elevated for each of the apo(a) phenotypes examined. The effects of the apo(a) and low density lipoprotein receptor genes on Lp(a) levels are not additive but multiplicative. This is a situation not commonly considered in quantitative human genetics. We conclude that Lp(a) levels in plasma may be determined by variation at more than one gene locus.     

Presence of oxidized low density lipoprotein in nonrheumatic stenotic aortic valves.

The aim of the present study was to analyze if LDL particles trapped in stenotic aortic valve tissue undergo oxidative modification. Degenerative aortic stenosis affects >3% of the population >75 years of age in the Western world. Recent studies have revealed the presence of a chronic inflammatory process similar to what has been described in other degenerative diseases such as atherosclerosis. However, the underlying disease mechanisms of degenerative aortic stenosis still remain largely unknown. Six tricuspid stenotic valves, obtained at valve replacement, were compared with 3 control valves collected from hearts taken out during transplantation. The stenotic valves and the control valves were examined by immunohistochemistry, using antibodies against apoB, 4-hydroxynonenal-modified LDL, leukocytes, and HLA-DR. All valves were also stained with oil red O for neutral lipids. Extracellular neutral lipids were found in all stenotic valves, extending from the bases along the fibrosa layer. This lipid colocalized with apoB- and 4-hydroxynonenal-modified LDL immunoreactivity. 4-Hydroxynonenal-modified LDLs were present around calcium deposits, subendothelially, and in the deeper layer of the fibrosa. There was also a colocalization with macrophages, T lymphocytes, and HLA-DR expression. Control valves had a thin area of neutral lipid accumulation, a small amount of apoB, but no signs of inflammation. A distinct colocalization between oxidized LDLs, T-lymphocyte accumulation, and calcium deposits suggests that oxidized lipids may play a role in the disease process.     

高密度脂蛋白组分修饰参与动脉粥样硬化发生发展的研究进展

高密度脂蛋白(HDL)作为体内保护心血管系统的重要物质,可通过多种途径拮抗动脉粥样硬化(As)进展。然而,在病理状态下,氧化、糖化、甲基化修饰及微小核糖核酸(miRNA)修饰可引起HDL组分出现结构改变和功能障碍。本文重点综述了HDL功能组分及其修饰与As关系研究进展,此方面研究对于探寻As诊断和治疗潜在靶点具有重要意义。     

High density lipoprotein cholesterol levels are an independent predictor of the progression of chronic kidney disease

Objectives

Patients with chronic kidney disease (CKD) often present with reduced plasma HDL cholesterol (HDL‐C) levels. Whether this reduction in an epiphenomenon or is involved in disease progression is unclear. The aim of this study was to investigate the relation between HDL‐C levels/function and CKD progression in patients with different degrees of disease.

Design

A total of 176 patients with CKD [glomerular filtration rate (GFR) 50.3 ± 29.1 mL min^?1] were recruited and followed for up to 84 months. Lipid profile, metabolic status and kidney function were evaluated at predetermined times. Age‐matched control subjects were selected from the PLIC study (n = 453). Scavenger receptor class B member 1 (SR‐BI) and ATP‐binding cassette transporter A1 (ABCA‐1)‐dependent efflux of cholesterol were measured in CKD patients and in age‐matched control subjects.

Results

Low HDL‐C levels, diabetes and hypertension were associated with reduced GFR. At follow‐up, low HDL‐C levels were associated with earlier entry in dialysis or doubling of the plasma creatinine level (P = 0.017); HDL‐C levels were the only lipid parameter that affected the progression of CKD (hazard ratio 0.951, 95% confidence interval 0.917–0.986, P = 0.007), independently of the presence of diabetes. Only SR‐BI‐mediated serum cholesterol efflux was significantly reduced in the group of CKD patients with low HDL‐C levels compared to the control group.

Conclusions

CKD patients with low levels of plasma HDL‐C have a poor prognosis. HDL functionality is also impaired in renal dysfunction. These data support the relevance of HDL in influencing CKD progression.

     

High vitamin E plasma levels and low low-density lipoprotein oxidation are associated with the absence of atherosclerosis in octogenarians

OBJECTIVES: To identify the biological characteristics of older subjects with vascular successful aging (VASA), defined as the absence of instrumental signs and clinical symptoms of atherosclerosis in the extracoronary and coronary vessels. DESIGN: A cross-sectional study. SETTING: A university-affiliated outpatient clinic. PARTICIPANTS: Sixty older subjects (30 with VASA and 30 controls with moderate carotid atherosclerosis (AG group)) from a sample of 705 subjects age 75 and older consecutively screened. MEASUREMENTS: Clinical examination; ultrasonographic examination of carotid, vertebral, abdominal aortic, iliac, and femoral arteries; electrocardiogram; and laboratory evaluation (lipid profile, lipophilic antioxidants, and markers of low-density lipoprotein (LDL) oxidation). RESULTS: Compared with controls, there were more females in the VASA group (82% vs 50%, P <.01), and fewer previous smokers (20.5% vs 52.5%, P <.01). Vitamin E/total cholesterol levels both in plasma (4.81 vs 3.51 micromol/mmol, P <.001) and in isolated LDLs (2.71 vs 1.86 microg/mg LDL cholesterol (LDL-C), P <.01), were higher in the VASA group, as was the resistance of LDLs to in vitro oxidation (as indicated by a longer duration of the lag phase: 80.2 vs 65.6 minutes, P <.001). The level of fluorescent products of lipid peroxidation (FPLPs) in native LDLs was lower in the VASA group (13.5 vs 18.8 URF/mg LDL-C, P <.001). Multivariate logistic regression analysis showed that only plasma vitamin E level (odds ratio (OR) = 6.04, 95% confidence interval (CI) = 1.48-24.63) and FPLPs in LDLs (OR = 0.53, 95% CI = 0.31-0.91) were independently associated with VASA. CONCLUSIONS: These results suggest that an appropriate level of vitamin E and a low level of LDL oxidation might be important for reaching advanced age without developing atherosclerosis.     

Serum copper levels in patients with acute and chronic types of ischemic heart disease and its relation to lipoprotein levels and extent of coronary atherosclerosis

The authors assessed serum copper and lipoprotein concentrations in a group of 67 patients hospitalized successively at the cardiological department. During hospitalization they were subjected to selective coronarography with assessment of the angiographic score. In 35 patients the angiographic examination was made during the chronic stage of IHD (group A), in 32 patients it was indicated on account of acute coronary syndrome (group B). The authors found that serum copper concentrations are significantly higher in patients with acute forms of IHD (group B, p < 0.001). Serum copper concentrations do not correlate significantly with lipoprotein concentrations nor with the extent of coronary atheroclerosis (angiographic score).     

Low density lipoprotein retention by aortic tissue. Contribution of extracellular matrix

We compared in vitro heparin binding activity and in vivo intravascular clearance and aortic uptake in rabbits of native, reductively methylated and heparin-complexed low density lipoprotein (LDL) in order to explore the extracellular matrix binding vs cellular metabolism of LDL. Reductively methylated LDL formed soluble and insoluble complexes with heparin which was comparable to native LDL. Reductive methylation of LDL produced only 30% reduction in aortic uptake vs 60% reduction in plasma clearance, reflecting the relatively smaller contribution of receptor-mediated pathway in aortic tissue vs whole animal. The intravascular clearance of native and heparin-complexed LDL remained essentially the same, indicating similarities in cellular metabolism of LDL in both cases. But the aortic uptake of the heparin bound LDL was 30% less than the native LDL, suggesting an inhibition in binding of heparin-complexed LDL to tissue proteoglycans. Saline extraction accounted for only part (53-66%) of the LDL preparations that were retained by the tissue while subsequent collagenase and elastase treatments extracted 3-5% and 17-22% of the materials respectively. These results favor the contribution of arterial extracellular matrix components to the retention of LDL.     

Immunization with bacillus Calmette-Guerin vaccine increases aortic atherosclerosis in the cholesterol-fed rabbit

New Zealand White rabbits were injected subcutaneously with either a human dose of bacillus Calmette Guerin (BCG) vaccine (n = 7) or saline (n = 7). A further half dose of BCG or saline was injected after a further 4 weeks. The animals were subsequently fed a 0.25-1% cholesterol diet for 10 weeks, 8 weeks after the first injection. The rabbits were killed and perfusion fixed with 4% paraformaldehyde. The integrated plasma cholesterol levels did not differ significantly between the groups (P > 0.05). Plasma levels of anti-mycobacterial antibodies rose following BCG immunization, reaching a peak after 8 weeks (P < 0.05) compared to basal titers and the control group. BCG immunization was also associated with increased peripheral lymphocyte and monocyte activation, as evidenced by increased surface expression of IL-2 receptor (CD25) (P < 0.02) and MAC-I (CD11b) (P < 0.05), respectively. Significantly more mononuclear cells bound to the aortic endothelium of BCG immunized, cholesterol-fed rabbits (1.93+/-0.77 mononuclear cells/1000 endothelial cells) than to that of saline immunized rabbits (0.08+/-0.08 mononuclear cells/1000 endothelial cells; P < 0.01). The aortic intimal:medial ratio was greater in the BCG immunized rabbits (0.19+/-0.08) than those treated with saline (0.04+/-0.03; P < 0.05). This suggests that BCG immunization enhances peripheral leucocyte activation, aortic monocyte recruitment and atherogenesis in the cholesterol-fed rabbit.