Canine hyperlipoproteinemia and atherosclerosis. Accumulation of lipid by aortic medial cells in vivo and in vitro.

Dogs maintained for 1 year on a semisynthetic diet containing hydrogenated coconut oil and cholesterol developed hypercholesterolemia. In those cases where plasma cholesterol levels exceeded 750 mg/100 ml, the animals also developed severe atherosclerosis. This atherogenic hyperlipoproteinemia was characterized by the presence of beta very low density lipoproteins (B-VLDL), increased levels of low density lipoproteins (LDL), and the occurrence of the HDLc lipoproteins. In all of these cholesterol-rich lipoproteins the arginine-rich apoprotein (ARP) was prominent. Moreover, the HDLc (d = 1.006-1.02) contained the ARP as the only detectable apoprotein. The atherosclerosis involved the abdominal aorta, coronary and cerebrovascular arteries, and many of the peripheral arteries. Histologically, the aortic lesions were characterized by a variable intimal proliferative response and extensive medial lipid deposition. In the peripheral, coronary, and cerebral arteries, the lesions were more extensive and involved primarily the media of the vessel wall, with little intimal reaction in many cases. The correlation between the in vivo disease process and the response of aortic smooth muscle cells (SMC) grown in tissue culture to the various cholesterol-induced lipoproteins was examined. B-VLDL, LDL, and HDLc (but not HDL2) caused a marked accumulation of free and esterified cholesterol in the SMC. The cholesterol accumulation was found to be more extensive in canine SMC than in swine smooth muscle cells or smooth muscle cells of other species in response to a similar lipoprotein cholesterol concentration. The enhanced sterol uptake appeared to be a property of canine smooth muscle cells rather than a property of the canine lipoproteins. These in vitro results may be related to the observed propensity for the development of medical disease that was demonstrated in the in vivo studies.     

The effect of cholesterol oxidation products on the disruption of lipid metabolism and atherosclerotic damage of the aorta in rabbits

Feeding of rabbits with a cholesterol preparation containing 3-5% of cholesterol autooxidation products promotes elevation of plasma cholesterol and atherogenic low- and very-low-density lipoproteins as well as accumulation of neutral lipids (largely, of cholesterol ether) in hepatocytes and intramural arteries of the myocardium. The development of massive aortic lipoidosis can be also attributed to the intake of relevant products. The similar dose of non-oxidized cholesterol did not induce marked or any changes at all in rabbits lipid metabolism and aortic status. The evidence obtained indicates an essential role of food exogenic products of cholesterol oxidation in mechanisms of hypercholesterolemia development and atherosclerotic involvement of vascular walls.     

Triglyceride (TG) and remnant lipoproteins

Lowering low-density lipoprotein (LDL) cholesterol (LDL-C) can reduce the risk of cardiovascular disease (CVD) by approximately 30%, and the remaining 70% should be the second front of CVD risk reduction. Such residual risks include high triglyceride (TG) concentrations and low levels of high-density lipoprotein (HDL) cholesterol (HDL-C) in terms of dyslipidemia. TG-rich lipoproteins are heterogenous and composed of a variety of subfractions, all of which are not necessarily relevant to atherosclerosis and CVD risk. However, remnant lipoproteins, TG-rich lipoproteins, are atherogenic and related to CVD risk. Two different methods (RLP-C and RemL-C) have been developed to measure cholesterol levels of remnant lipoproteins. Although there is a difference in affinity to intermediate-density lipoprotein (IDL) between the two methods, they may be better qualified as biomarkers of CVD risk than TG itself. TG measurements play a certain role in the evaluation of CVD risk, but the remnant lipoprotein cholesterol measurement can provide better screening for patients at high CVD risk than TG and may be a useful examination in both quantity and quality.     

Effects of low-density lipoprotein from normal rabbits on hypercholesterolemia and the development of atherosclerosis

To clarify whether or not normal LDL separated from normal rabbits is atherogenic, 0.75 mg of normal LDL-cholesterol in 6 ml of 0.85% saline and 6 ml of saline alone were injected every day for 5 weeks into the auricular vein of two groups of rabbits, respectively. The inoculated rabbits were fed a standard diet containing 0.5 and 1% cholesterol. Blood was drawn before injection and at 1, 2, 3 and 5 week intervals thereafter. After 5 weeks, all rabbits were sacrificed. Following exsanguination, the aorta was stained by Sudan III. The Sudan III staining was more extensive in rabbits injected with saline than in those that received LDL. In addition, plasma cholesterol, plasma phospholipid, VLDL-cholesterol and LDL-cholesterol levels were lower in LDL-injected rabbits than in those injected with saline. But HDL-cholesterol levels were not significantly different between LDL-cholesterol and saline-injected rabbits. Although the exact cause of antiatherogenic effect of normal LDL is not clear, it seems reasonable to suggest that at least some normal LDL acts as a 'good' lipoprotein, namely antiatherogenic lipoprotein, in our experimental protocol.     

Lipid peroxidation in the etiology and pathogenesis of atherosclerosis

Reviewing the data available in the literature and their own findings, the authors consider the role of lipid peroxidation in the etiology and pathogenesis of atherosclerosis. The paper provides a good evidence for intensified peroxidation of hepatic lipids and liver-secreted atherogenic lipoproteins in atherogenesis, which is followed by blood lipid peroxides accumulation in hypercholesterolemia and atherosclerosis. The excess of aortic lipid peroxides occurs concurrently with a sharp decrease in the activity of the enzymatic systems in utilizing lipid peroxides. Accumulation of lipid peroxides in the aorta may be a factor that contributes to higher migration and proliferation of smooth muscle cells forming a cellular basis for an atherosclerotic plaque. The products of cholesterol oxidation were also reported to exert an atherogenic action.     

Hyperlipoproteinaemia and atherosclerosis in rabbits fed low-level cholesterol and lecithin

Dutch-Belted rabbits were fed for 18 months an atherogenic semipurified gel diet containing 14% hydrogenated coconut oil and 0.06% cholesterol (approximately 0.15 mg/kcal) or a non-atherogenic basal gel diet containing the same ingredients but with no coconut oil or cholesterol. Rabbits fed atherogenic diet developed hypercholesterolaemia (means 733 mg/dl at 16 months) and plasma lipoprotein (LP) distribution shifted from a pattern in which high-density lipoproteins (HDL) predominated to one in which very-low-density lipoproteins (VLDL) were predominant. Total cholesterol/triglyceride ratio in d less than 1.006 LP changed from 0.3 to 1.8. Plasma cholesterol and LP distribution returned to normal in rabbits fed atherogenic diet for 18 months followed by atherogenic diet plus 3% soya lecithin for an additional 4 months. Rabbits fed atherogenic diet for 18 months had extensive, usually full circumference fibromuscular plaques in main branches of coronary arteries and all portions of aorta which compromised lumen area by almost 50%. These lesions were modified in rabbits fed atherogenic diet plus lecithin. The plaques lacked foam cells and cholesterol clefts, were less cellular with a distinct fibrous surface and occupied less space. Animals fed basal diet did not develop hypercholesterolaemia (means 86 mg/dl at 16 months), although distribution of plasma LP shifted slightly in favour of increased low-density lipoproteins (LDL) and decreased HDL compared with rabbits fed standard commercial diet. Basal diet rabbits had no coronary atherosclerosis and only minimal focal foam cell lesions in proximal aorta. Liver injury including fatty change, cholangitis and portal fibrosis occurred in animals fed atherogenic diet. Thus, rabbits fed appropriate diets low in cholesterol accumulate cholesterol-enriched LP in their plasma and develop lesions in abdominal aorta and main branches of coronary arteries which are similar to those in man. Also, in this experimental model, dietary lecithin promotes a return to normal of the LP distribution profile and removal of lipid from established atherosclerotic plaque.     

Hyperlipoproteinaemia and atherosclerosis in rabbits fed low-level cholesterol and lecithin.

Dutch-Belted rabbits were fed for 18 months an atherogenic semipurified gel diet containing 14% hydrogenated coconut oil and 0.06% cholesterol (approximately 0.15 mg/kcal) or a non-atherogenic basal gel diet containing the same ingredients but with no coconut oil or cholesterol. Rabbits fed atherogenic diet developed hypercholesterolaemia (means 733 mg/dl at 16 months) and plasma lipoprotein (LP) distribution shifted from a pattern in which high-density lipoproteins (HDL) predominated to one in which very-low-density lipoproteins (VLDL) were predominant. Total cholesterol/triglyceride ratio in d less than 1.006 LP changed from 0.3 to 1.8. Plasma cholesterol and LP distribution returned to normal in rabbits fed atherogenic diet for 18 months followed by atherogenic diet plus 3% soya lecithin for an additional 4 months. Rabbits fed atherogenic diet for 18 months had extensive, usually full circumference fibromuscular plaques in main branches of coronary arteries and all portions of aorta which compromised lumen area by almost 50%. These lesions were modified in rabbits fed atherogenic diet plus lecithin. The plaques lacked foam cells and cholesterol clefts, were less cellular with a distinct fibrous surface and occupied less space. Animals fed basal diet did not develop hypercholesterolaemia (means 86 mg/dl at 16 months), although distribution of plasma LP shifted slightly in favour of increased low-density lipoproteins (LDL) and decreased HDL compared with rabbits fed standard commercial diet. Basal diet rabbits had no coronary atherosclerosis and only minimal focal foam cell lesions in proximal aorta. Liver injury including fatty change, cholangitis and portal fibrosis occurred in animals fed atherogenic diet. Thus, rabbits fed appropriate diets low in cholesterol accumulate cholesterol-enriched LP in their plasma and develop lesions in abdominal aorta and main branches of coronary arteries which are similar to those in man. Also, in this experimental model, dietary lecithin promotes a return to normal of the LP distribution profile and removal of lipid from established atherosclerotic plaque.     

The vasoactive properties of different classes of blood lipoproteins in hypercholesterolemia and atherosclerosis

Studies were made of the effects of various classes of lipoproteins (LP) from the blood of rabbits with experimental hypercholesterolemia and human subjects with pronounced atherosclerosis on the vascular tone of rat thoracic aorta specimens. In hypercholesterolemia, there was a considerable weakening of a vasodilatory action of atherogenic LP fractions--LDL and VLDL. A vasodilatory effect of HDLP was not changed. In subjects suffering from atherosclerosis vasodilatory effects of both atherogenic and antiatherogenic HDLP decreased significantly. The revealed changes were related to shifts in lipid and protein components of LP complexes manifesting in the development of dyslipoproteinemia and dysapoproteinemia. In atherosclerosis accompanied with more profound changes suppression of vasodilatory effects of LP is greater than in transient experimental hypercholesterolemia. Consequently, changes of lipid and apo composition of LP and weakening of their vasodilatory action play a considerable role in the vessel tone changes in atherogenic situation.     

Role of hepatic and lipoprotein lipase in lipoprotein metabolism and atherosclerosis: studies in transgenic and knockout animal models and somatic gene transfer

Hepatic lipase (HL) and lipoprotein lipase (LPL) are the two major lipolytic enzymes responsible for the hydrolysis of triglycerides and phospholipids present in circulating plasma lipoproteins. Both lipases are attached to the vascular endothelium via cell surface proteoglycans. HL is primarily involved in the metabolism of chylomicron remnants, intermediate density lipoproteins and high-density lipoproteins whereas LPL catalyzes the hydrolysis of triglycerides from chylomicrons and very low-density lipoproteins. In addition to their traditional function as lipolytic enzymes, HL and LPL appear to serve as ligands that mediate the interaction of lipoproteins to cell surface receptors and/or proteoglycans. Over the past several years significant advances have been made in our understanding of new, alternative mechanisms by which HL and LPL modulate lipoprotein metabolism and the development of atherosclerosis in vivo. This review will summarize some of the new insights generated from the study of transgenic and knockout HL and LPL animal models as well as somatic gene transfer of these two lipases.     

The in vitro interactions between serum lipoproteins and proteoglycans of the neointima of rabbit aorta after a single balloon catheter injury.

The effect of injury-induced alterations in the aortic neointimal proteoglycans on their binding with homologous serum lipoproteins was examined. Proteoglycans of the aortic intimal-medial tissues of rabbits that had undergone denudation with a balloon catheter 12 weeks earlier were isolated after homogenization of the tissues in 0.33 M sucrose, ultracentrifugation and subsequently by gel-exclusion chromatography. Lipoproteins from the plasma of healthy donors were prepared by sequential, ultracentrifugal floatation after density adjustment with KBr. To study the interactions, aliquots of electrophoretically pure very low-density lipoproteins (VLDL, d less than 1.006 g/ml), low-density lipoproteins (LDL, d = 1.019-1.063 g/ml), or high-density lipoproteins (HDL, d = 1.210 g/ml) were incubated with proteoglycans in the presence of Ca++ and Mg++ at 4 C. The amount of cholesterol found in the resulting pellet was measured as a marker of the binding capacity of the proteoglycans. Among lipoprotein fractions both VLDL and LDL showed strong binding with proteoglycans, whereas no appreciable binding was observed when incubation experiments were done with HDL. There were significant differences in the lipoprotein binding capacity of proteoglycan of control and injured animals, indicating that injury induced changes in proteoglycan composition exert profound influences on their ionic interactions.     

Diet induced atherogenic hyperlipoproteinaemia and liver injury in cynomolgus macaques.

This study was conducted to determine the efficacy of an experimental anti-atherosclerosis drug in the adult male cynomolgus monkey. A semipurified diet containing 0.5% cholesterol and 25.5% butter was fed to groups of 20, each, drug and placebo-treated animals for 18 months. Similar liver and arterial changes were present in both groups. However, we report here tissue changes seen in animals given placebo only, with plasma lipid and lipoprotein values of placebo-treated animals compared to those in animals fed nonatherogenic commercial ration. Animals fed atherogenic diet had enlarged livers (mean 3.9% b.w.), and all had evidence of hepatocellular lipid accumulation which was often marked and diffuse. Cholangitis was common including mononuclear cell infiltration, bile ductule proliferation and portal tract fibrosis. Five animals had severe portal fibrosis with bands of connective tissue extending into and around lobules (bridging fibrosis). All animals fed atherogenic diet developed hypercholesterolemia (greater than 600 mg/dl) which was the result of a three-fold increase in five cholesterol and cholesterol ester. Oleic acid was increased and linoleic acid was reduced in plasma phospholipids and cholesterol esters. Plasma lipoprotein distribution was altered with a marked increase in low density lipoproteins, increased very low density lipoproteins and decreased high density lipoproteins. These changes were undoubtedly caused by diet, i.e., high in cholesterol and saturated fat and limiting in linoleic acid. It is probable that diet-induced liver injury would affect the pathogenesis of atherosclerosis in this model since the liver is central in the synthesis and metabolism of lipoproteins.     

Overexpression of human lecithin:cholesterol acyltransferase in mice offers no protection against diet-induced atherosclerosis

Human lecithin:cholesterol acyltransferase (LCAT) is a key enzyme in the metabolism of cholesterol. We have used homozygous transgenic mice overexpressing the human LCAT transgene to study the effect of a "Western-type" atherogenic diet (30% fat, 5% cholesterol and 2% cholic acid) on their LCAT expression, activity, lipoprotein profile and tendency to develop atherosclerosis. The LCAT activity was 35-fold higher in serum of the homozygous transgenic mice than in murine control serum, and decreased 11-20% in the transgenic mice when fed the atherogenic diet. The total cholesterol and high-density lipoprotein cholesterol (HDL-C) concentrations were approximately doubled in the transgenic mice compared with the controls when both groups were fed a regular chow diet. In mice on the atherogenic diet, the triglyceride concentration decreased about 50% to the same level in transgenic and control mice. Total cholesterol and HDL-C concentrations increased and were 60-80% higher in the transgenic mice. The expression of LCAT mRNA in the liver was decreased by 49-60% in the transgenic mice when fed the atherogenic diet. The development of atherosclerosis was similar in transgenic and control mice. Thus, the 14- to 27-fold higher LCAT activity and the higher HDL-C concentrations in the homozygous LCAT transgenic mice had no significant protective influence on the development of diet-induced atherosclerosis.     

Effects of diltiazem on suppression and regression of experimental atherosclerosis

The effects of diltiazem (a calcium antagonist) on the suppression and regression of atherosclerosis were studied. Thirty-one rabbits were fed a 1% cholesterol (atherogenic) diet together with saline (n = 22) or diltiazem (n = 9) injections. After 10 weeks, seven rabbits that received saline and nine rabbits that received diltiazem were killed. The remaining 15 saline-treated rabbits were then put on a standard (regression) diet for the next 15 weeks with saline (n = 7) or diltiazem (n = 8) injections. Sixteen rabbits given a standard diet were used as controls. At 5 and 10 weeks, the plasma LDL cholesterol level in rabbits on the atherogenic diet with diltiazem was significantly lower than in those on the atherogenic diet with saline. The aortic total cholesterol, esterified cholesterol and calcium contents were also significantly lower in rabbits on the atherogenic diet with diltiazem. After 25 weeks (15 weeks on the regression diet), the differences in aortic total cholesterol and calcium contents between the two groups on the regression diet were not significant; however, the aortic esterified cholesterol content was significantly lower in the regression diet with diltiazem. The results suggest that diltiazem has a favourable effect both on regression and on suppression of atherosclerosis.     

Diet induced atherogenic hyperlipoproteinaemia and liver injury in cynomolgus macaques

This study was conducted to determine the efficacy of an experimental anti-atherosclerosis drug in the adult male cynomolgus monkey. A semipurified diet containing 0.5% cholesterol and 25.5% butter was fed to groups of 20, each, drug and placebo-treated animals for 18 months. Similar liver and arterial changes were present in both groups. However, we report here tissue changes seen in animals given placebo only, with plasma lipid and lipoprotein values of placebo-treated animals compared to those in animals fed nonatherogenic commercial ration. Animals fed atherogenic diet had enlarged livers (mean 3.9% b.w.), and all had evidence of hepatocellular lipid accumulation which was often marked and diffuse. Cholangitis was common including mononuclear cell infiltration, bile ductule proliferation and portal tract fibrosis. Five animals had severe portal fibrosis with bands of connective tissue extending into and around lobules (bridging fibrosis). All animals fed atherogenic diet developed hypercholesterolemia (greater than 600 mg/dl) which was the result of a three-fold increase in five cholesterol and cholesterol ester. Oleic acid was increased and linoleic acid was reduced in plasma phospholipids and cholesterol esters. Plasma lipoprotein distribution was altered with a marked increase in low density lipoproteins, increased very low density lipoproteins and decreased high density lipoproteins. These changes were undoubtedly caused by diet, i.e., high in cholesterol and saturated fat and limiting in linoleic acid. It is probable that diet-induced liver injury would affect the pathogenesis of atherosclerosis in this model since the liver is central in the synthesis and metabolism of lipoproteins.     

Effects of diltiazem on suppression and regression of experimental atherosclerosis.

The effects of diltiazem (a calcium antagonist) on the suppression and regression of atherosclerosis were studied. Thirty-one rabbits were fed a 1% cholesterol (atherogenic) diet together with saline (n = 22) or diltiazem (n = 9) injections. After 10 weeks, seven rabbits that received saline and nine rabbits that received diltiazem were killed. The remaining 15 saline-treated rabbits were then put on a standard (regression) diet for the next 15 weeks with saline (n = 7) or diltiazem (n = 8) injections. Sixteen rabbits given a standard diet were used as controls. At 5 and 10 weeks, the plasma LDL cholesterol level in rabbits on the atherogenic diet with diltiazem was significantly lower than in those on the atherogenic diet with saline. The aortic total cholesterol, esterified cholesterol and calcium contents were also significantly lower in rabbits on the atherogenic diet with diltiazem. After 25 weeks (15 weeks on the regression diet), the differences in aortic total cholesterol and calcium contents between the two groups on the regression diet were not significant; however, the aortic esterified cholesterol content was significantly lower in the regression diet with diltiazem. The results suggest that diltiazem has a favourable effect both on regression and on suppression of atherosclerosis.     

Dietary induced hyperbetalipoproteinemia in chimpanzees: comparison to the human hyperlipoproteinemia

Fasting plasma from chimpanzees fed normal and atherogenic diet was separated into alpha (HDL) and beta (LDL) lipoproteins by electrochromatography. Both lipoproteins were analyzed for lipid and fatty acid composition.Beta lipoproteins, esterified cholesterol, free cholesterol, and phospholipids were increased in chimpanzees fed the atherogenic diet. The cholesterol/phospholipid ratio was increased. These lipid changes occurred chiefly in the beta lipoproteins. A disproportionate increase of plasma phosphatidylcholine to sphingomyelin was confirmed. Differences in the fatty acid composition of both lipoproteins were noted and cholesterol oleate was elevated more than cholesterol linoleate so that the $\text{18:1}\text{18:2}$ ratio was increased. The intima of one animal which died from myocardial infarction after 4–5 years diet showed an increase of cholesterol oleate.Similarities between cholesterol-induced lipoprotein changes in chimpanzees and those obtained in human hyperbetalipoproteinemia are discussed. These similarities stress the usefulness of these nonhuman primates as a model for experimental atherosclerosis and for studying the molecular changes in lipoprotein patterns.     

Effect of remote aortic injury and thrombosis on cholesterol atherosclerosis

Recent tissue culture studies indicate that platelet factors enhance lipoproteins to stimulate proliferation of smooth muscle cells, a key event in atherogenesis. It was of interest to determine if continued remote aortic injury and thrombosis can increase the severity of hypercholesterolemia induced atherosclerosis. Four groups of rabbits were studied, two groups fed 0.5 g cholesterol per day, one group with and one group without massive abdominal aortic white mural non-occlusive thrombosis and injury induced with a permanent indwelling catheter, and two groups fed 1 g cholesterol per day, one group with and one group without similar thrombosis and injury. Serum lipids in the four groups were qualitatively and quantitatively not significantly different from each other at 4, 8, and 12 weeks. When they were sacrificed at 12 weeks the percent intimal surface area in the thoracic aorta (48 ± 22) and arch (75 ± 28) of the rabbits with thrombosis and fed 0.5 g cholesterol per day was significantly (p < 0.01) greater than the percent intimal area (20 ± 14) and (24 ± 18) of the rabbits without thrombosis. The percent intimal area with lesions in the rabbits fed 1 g cholesterol per day with thrombosis (59 ± 25) and (84 ± 30) was significantly greater (p < 0.01) than the percent area (24 ± 29) and (32 ± 32) of the rabbits without thrombosis. Since the effects could not be attributed to differing serum lipid levels it is possible that the increased severity of atherosclerosis in the remote arch and thoracic aorta was related to increased permeability, cell proliferation or collagen synthesis possibly stimulated by circulating factors released from the remote massive non-occlusive thrombus or from circulating platelets activated by contact with the injured abdominal aortic wall.     

Polyunsaturated phosphatidylcholine micelle-induced decrease of atherogenicity of the serumin vitro

It is shown that polyunsaturated phosphatidylcholine administered in micelles stabilized by a plant-derived glycoside prevents the accumulation of cholesterol by cells incubated in atherogenic serum and, moreover, in certain cases causes a 1.4–1.5-fold drop of intracellular cholesterol as compared to control cells. The optimum antiatherogenic effect was achieved when using a micelle concentration of 100–200 μg/ml and an incubation time of at least 4 hours. The antiatherogenic effect was analogous to the effect of high density serum lipoproteins. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 5 pp. 497–501, May, 1995 Presented by Yu. M. Lopukhin, Member of the Russian Academy of Medical Sciences     

Lipoprotein (a), low-density,intermediate-density lipoprotein,and blood pressure in a young male population

Summary Both hypercholesterolemia and hypertension are risk factors for atherosclerotic vascular disease, and elevated cholesterol levels occur more frequently than expected in patients with hypertension. Elevated levels of intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL) were shown to be atherogenic, and LDL, comprising the major cholesterol-carrying fraction in human plasma, are structurally related to lipoprotein (a) [Lp(a)], a further risk factor for atherosclerosis. In the present study we investigated 200 male employees (mean age 26±7 years) to determine whether the relationship of IDL and Lp(a) to systemic blood pressure is similar to the reported correlations between total and LDL cholesterol and systemic blood pressure. To this end blood pressure was measured several times in each individual, and lipids, lipoprotein-cholesterol, apolipoprotein B (apo B), and Lp(a) were determined in fasting serum. IDL cholesterol and apo B, the main protein component of IDL and LDL correlated with blood pressure. However, levels of Lp(a) correlated neither with systolic or diastolic blood pressure nor with lipoprotein cholesterol, body weight, or age. Although IDL and Lp(a) are considered lipoprotein risk factors for atherosclerosis, levels of Lp(a), unlike IDL, are not related to blood pressure, body weight, or age. Our data suggest different metabolic and pathophysiological mechanisms of the risk factors, IDL, LDL, and Lp(a).Abbreviations VLDL very low density lipoprotein - IDL intermediate-density lipoprotein - LDL low-density lipoprotein - ApoB Apolipoprotein B - Lp(a) lipoprotein (a) - BMI body mass index Dedicated to Prof. Dr. N. Zöllner on the occasion of his 70th birthday     

Lipoprotein analysis. Early methods in the diagnosis of atherosclerosis

Before 1950, there was no clear perception of the interrelationship of serum lipids, atherosclerosis, and coronary heart disease. Since then, research laboratories have made conflicting claims for the most useful measurement of the serum lipid levels in detecting and managing coronary heart disease. Emphasis has been placed in turn on the measurement of levels of serum cholesterol, lipoproteins, triglycerides, and, currently, cholesterol and lipoproteins again. Physical separation and characterization of serum lipoproteins by ultracentrifugation and electrophoresis resulted in two classification systems for lipoproteins based on hydrated density and electrophoretic mobility, respectively. Two operational by-products were the atherogenic index, an empirical formula supposed to correlate with coronary heart disease, and a phenotype system for classification of the lipoproteinemias. Current National Heart, Lung, and Blood Institute criteria for atherosclerosis risk implicate elevated levels of cholesterol and low-density lipoprotein cholesterol, and decreased levels of high-density lipoprotein cholesterol. Although triglycerides are closely associated with cholesterol in lipoprotein molecules and are positively associated with cardiovascular disease, there is no strong evidence of elevated levels of plasma triglycerides as an independent risk factor in coronary heart disease. Elevated levels of triglycerides can help identify persons with increased risk of cardiovascular disease from other causes, but screening for hypertriglyceridemia is not recommended. Apolipoproteins and lipoprotein Lp(a) are briefly discussed.