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Biomedical subjects

J R Patsch

Publications and source records attributed to J R Patsch.

At least 19 recordsLinked to original sources
PubMed1997

Complement activation by HIV-1-infected cells: the role of transmembrane glycoprotein gp41.

To characterize the mechanisms of complement activation by human immunodeficiency virus type 1 (HIV-1)-infected cells, Cl-4 cells stably expressing the envelope glycoproteins of HIV-1 and the parent African green monkey cell line CV-1 were tested for C1q binding and complement activation. While the parent cell line CV-1 only showed a weak spontaneous activation of the alternative pathway, Cl-4 cells additionally triggered the classical pathway of complement activation independent of anti-HIV antibodies by direct C1q binding. Earlier studies had shown different complement activating potential of cells infected with various HIV isolates. Recombinant soluble CD4-induced shedding of gp120 from the surface of HIV-1-infected cells converted a weak activator isolate (MVP-899) into a strong complement activator. The increase in complement activation was paralleled by the concomitant unmasking of a previously hidden gp41 epitope comprising the major complement-activating domain of gp41 (aa. 601-613). Our results strongly suggest that the transmembrane protein gp41 induces the activation of complement on the surface of infected cells as has been described previously for purified HIV-1 virions. Furthermore, we present evidence that the different potential of HIV isolates to activate the complement system on the cell surface is caused by different degrees of spontaneous gp120 shedding by various HIV isolates.

Animals↗
PubMed1996

Lipoprotein(a) is increased in triglyceride-rich lipoproteins in men with coronary heart disease, but does not change acutely following oral fat ingestion.

Association of apo(a)/Lp(a) with triglyceride-rich lipoproteins (TGR-Lps) is determined by different factors that are poorly understood. Some previous studies suggested that apo(a) in TGR-Lps may affect the atherogenicity of the TGR particles. To study whether there are any peculiarities in postprandial (pp) Lp(a) metabolism, we have determined apo(a) phenotypes and Lp(a) concentrations in 46 subjects with coronary heart disease (CHD) and in six normolipidemic individuals at different time points (4, 6 and 8 h) following an oral fat tolerance test. While mean triglyceride concentration reached its maximum 6 h after a standardized fat meal, no change in total cholesterol and in mean Lp(a) plasma concentration was detected at any time point after the fat load. In 6 normolipidemic probands and in 8 patients with CHD, who were matched for apo(a) phenotype, lipoprotein levels, age and body weight, we followed the distribution of apo(a) in plasma density gradient fractions in the fasting and pp state. In the CHD patients a significant larger percentage of apo(a) reactivity was detected in TGR-Lps in the pre- as well as in the postprandial state, compared to control subjects. The fat intake did not induce a significant change of apo(a) reactivity in the TGR-Lp fractions in both groups. The apo(a) isoform-size and the Lp(a) plasma concentration in the fasting state had no influence on the individual variation of the Lp(a) concentration in pp TGR-Lp fractions. Our results provide evidence that TGR-Lp fractions of CHD patients are enriched in apo(a) reactivity compared to healthy controls, but do not support the hypothesis that Lp(a) acts atherogenically through a pp increase of its plasma concentration.

Adult↗
PubMed1996

Effects of pancreas transplantation on distribution and composition of plasma lipoproteins.

In type I (insulin-dependent) diabetic patients, peripheral hyperinsulinemia due to subcutaneous insulin treatment is associated with increased high-density lipoprotein (HDL) cholesterol, and also with an altered surface composition of HDL. Pancreas grafts also release insulin into the systemic rather than into the portal venous system, giving rise to pronounced peripheral hyperinsulinemia. We hypothesized that if peripheral hyperinsulinemia is responsible for high HDL cholesterol and/or altered surface composition of HDL in diabetic subjects, similar changes in the lipid profile should be present in pancreas-kidney transplant recipients (PKT-R). Using zonal ultracentrifugation, we isolated HDL2, HDL3, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) from fasting plasma of 14 type I diabetic PKT-R, eight nondiabetic kidney transplant recipients (KT-R), and 14 healthy control subjects and determined the level and composition of the above lipoproteins. HDL2 cholesterol was increased in PKT-R as compared with KT-R and healthy controls (both P < .05), whereas HDL3 cholesterol was unchanged. However, an altered lipoprotein surface composition was evident in PKT-R: HDL2, HDL3, and LDL were enriched in unesterified cholesterol ([UC] PKT-R v KT-R, P=.13, P < .005, and P < .05, respectively; PKT-R v controls, all P < .005); HDL2 was enriched in phospholipids; and LDL was depleted of phospholipid. KT-R, in contrast, showed no changes in lipoprotein surface composition but a substantial triglyceride enrichment of HDL2 as compared with PKT-R and healthy controls (both P < .05). LDL size as determined by gradient gel electrophoresis was increased in PKT-R compared with controls (P < .005). The plasma concentration of cholesteryl ester (CE) transfer protein (CETP), involved also in phospholipid transfer, was increased in both transplant groups compared with healthy controls (both P < .05). Insulin concentrations in fasting plasma were directly related to CETP levels and to the weight-percentage of UC in HDL3, and inversely to the weight-percentage of phospholipids in LDL (all P < .05). We explain the increase in HDL2 cholesterol and LDL size in PKT-R by their high lipoprotein lipase (LPL) activity conferring an excellent capacity to clear chylomicron triglycerides. Effective handling of postprandial triglycerides, high HDL2 cholesterol, and predominance of LDL pattern A, respectively, are established indicators of a low risk of atherosclerosis. However, it is presently unclear what effects the compositional changes on the surface of HDL and LDL may have on cardiovascular risk in clinically stable PKT-R.

Adult↗
PubMed1996

The human immunodeficiency virus type 1 transmembrane gp41 protein is a calcium-binding protein and interacts with the putative second-receptor molecules in a calcium-dependent manner.

Fusion is a crucial event in the life cycle of the human immunodeficiency virus (HIV); is is initiated by the high-affinity binding between gp120, the external surface glycoprotein of HIV-1, and the differentiation antigen CD4 and finally results in the insertion of the hydrophobic amino terminus of the gp41 envelope glycoprotein into the plasma membrane of the target cell. Recent results suggest that this process is dependent upon calcium ions, but the mechanism or the proteins involved are not understood. Computer-assisted sequence analysis revealed a putative calcium-binding site within the extracellular part of gp41 that was highly reminiscent of the calcium-binding EF-hand structure. To test this hypothesis, calcium-binding experiments were performed. Binding of a recombinant soluble form of the transmembrane protein (rsgp41) to its putative second-receptor molecules in equilibrium was dependent upon calcium. The affinity was not influenced by calcium, but the maximum binding was increased in a dose-dependent manner. Radioactive calcium bound to rsgp41 covalently attached to Sepharose but not to bovine serum albumin. Binding was inhibited by the addition of nonradioactive calcium, indicating that binding was specific. Neither magnesium nor manganese inhibited the binding of labeled calcium to rsgp41. Binding was dependent on the oxidative state of the rsgp41 molecule, suggesting the functional importance of the correctly folded structure of the rsgp41 protein. In this report, we demonstrate that the HIV-1 transmembrane protein gp41 is a calcium-binding protein and interacts with the putative second-receptor molecules in a calcium-dependent manner.

Amino Acid Sequence↗
PubMed1996

Relationship of plasma cholesteryl ester transfer protein to HDL cholesterol. Studies in normotriglyceridemia and moderate hypertriglyceridemia.

To evaluate the independent effect of cholesteryl ester transfer protein (CETP) on HDL concentrations in humans, we measured lipids, lipoproteins, postprandial lipemia after an oral fat load, CETP mass, and the activities of CETP, lipoprotein lipase (LPL), and hepatic lipase in 16 healthy, normotriglyceridemic men and in 23 men with moderate, primary hypertriglyceridemia on an American Heart Association Step I diet. Fasting triglycerides and postprandial lipemia were increased and HDL cholesterol (HDL-C) was decreased in hypertriglyceridemic men compared with control subjects (P < .001). In the normotriglyceridemic group, CETP mass (P < .001) and activity (P < .005) were directly related to LPL activity After statistical adjustment for this close association, no significant relationship of CETP to HDL-C independent of LPL activity could be demonstrated in the normotriglyceridemic subjects. In contrast, CETP was unrelated to LPL activity in the hypertriglyceridemic subjects, but CETP concentrations showed a close inverse relationship to HDL-C (r = -.504, P = .014). Structural equation modeling of the association structures between HDL and fasting and postprandial triglycerides, endothelial lipases, and CETP in both groups indicated that the overall regression models for the two groups differed (P < .05). Specifically, the associations between CETP mass and activity and HDL-C differed between both groups (both P < .01). We conclude that high-normal CETP levels lower HDL-C in nonsmoking, nonobese men with moderate, primary hypertriglyceridemia on a hypolipidemic diet, but not in healthy, normotriglyceridemic men on an unrestricted diet. Thus, variation in CETP plasma concentrations may contribute to the high-triglyceride, low-HDL phenotype.

Adult↗
PubMed1996

Apolipoprotein A-II influences the substrate properties of human HDL2 and HDL3 for hepatic lipase.

Hepatic lipase has a demonstrated dual role in plasma lipid transport in that it participates in the removal of remnants of triglyceride-rich lipoproteins from the circulation and in the metabolism of plasma HDL. The study presented here investigated the substrate properties for hepatic lipase of HDL differing in density and apolipoprotein (apo) composition. Rates of fatty acid liberation were twofold higher in HDL2 compared with the respective HDL3 subspecies. Within each density class, enzyme-catalyzed fatty acid release was nearly twofold higher from HDL containing apoA-II compared with HDL devoid of apoA-II. When native HDL3 devoid of apoA-II was reconstituted with dimeric apoA-II in vitro, rates of fatty acid liberation in reconstituted particles were similar to those in native HDL3 containing apoA-II. HDL containing apoA-II competed more effectively with small VLDL for binding of hepatic lipase than HDL devoid of apoA-II. HDL3, particularly apoA-II-containing HDL3, reduced lipolysis of triglyceride and total fatty acid liberation in small VLDL. We conclude that the substrate properties of HDLs for hepatic lipase are influenced by both their size and apoA-II content. Moreover, size as well as apoA-II content may indirectly affect remnant clearance.

Apolipoprotein A-II↗
PubMed1995

Relationship of high-density lipoprotein subfractions and cholesteryl ester transfer protein in plasma to carotid artery wall thickness.

High plasma concentrations of high-density lipoprotein (HDL) cholesterol are a powerful indicator of low vascular risk. By decreasing HDL cholesterol, cholesteryl ester transfer protein (CETP) could perhaps constitute an atherogenic protein. We measured HDL cholesterol and HDL subfractions and quantified CETP mass in fasting plasma in 21 asymptomatic probands, and related these variables to the mean intima media thickness of the extracranial carotid arteries. HDL2 cholesterol, the less dense HDL subfraction, was inversely related to carotid wall thickness (r = -0.378; P < 0.05), and CETP was directly related to carotid wall thickness (r = 0.436; P < 0.05). In plasma CETP is associated mostly with the HDL3 subfraction. We therefore calculated from our measurements the relative CETP content of HDL3, i.e., CETP/HDL3 cholesterol. This ratio was correlated with carotid wall thickness stronger than any other variable measured (r = 0.718, P < 0.001). We conclude that variation in HDL subfractions and CETP may be more closely associated with carotid intima media thickness than the accepted strong risk factor of HDL cholesterol.

Adult↗
PubMed1995

Treatment of primary mixed hyperlipidemia with etophylline clofibrate: effects on lipoprotein-modifying enzymes, postprandial lipoprotein metabolism, and lipoprotein distribution and composition.

In 17 patients with primary mixed hyperlipidemia we studied levels and composition of lipoproteins in fasting plasma, lipoprotein-modifying enzymes, and postprandial lipoprotein metabolism after an oral fat-tolerance test supplemented with vitamin A before, and 12 weeks after treatment with etophylline clofibrate. With treatment, fasting plasma cholesterol, triglycerides, and the levels of very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and low density lipoproteins (LDL) decreased significantly; high density lipoprotein (HDL) cholesterol increased significantly. Treatment caused also an increase in the protein content of IDL, a decrease in the triglyceride content of LDL, and an increase in the size of LDL as assessed by gradient gel electrophoresis. Concentrations of triglycerides, chylomicrons, and chylomicron remnants after an oral fat load supplemented with vitamin A decreased by 33%, 30% and 6%, respectively (P < 0.005; P < 0.01; and P < 0.05). The activity of lipoprotein lipase and hepatic lipase in postheparin plasma increased by 51% and 45%, respectively (P < 0.01; P < 0.05). We found a decrease in the mass concentration of cholesteryl ester transfer protein (P < 0.05). Stepwise multiple regression analysis showed that the triglyceride content of LDL is determined primarily by fasting triglycerides (r = + 0.53, P < 0.05;baseline) and cholesteryl ester transfer protein (r = + 0.49, P < 0.05; 12 weeks); in contrast, the triglyceride content of HDL3 is determined exclusively by accumulation of postprandial triglycerides (r = + 0.67; P < 0.05; baseline) and postprandial chylomicrons (r = +0.87; P < 0.005; 12 weeks). We conclude that hypolipidemic treatment with etophylline clofibrate favorably affects the cardiovascular risk factor profile in primary mixed hyperlipidemia.

Carrier Proteins↗
PubMed1995

Sera from HIV-1 infected individuals in all stages of disease preferentially recognize the V3 loop of the prototypic macrophage-tropic glycoprotein gp120 ADA.

The outer membrane glycoprotein gp120 and the transmembrane glycoprotein gp41 are predominant targets of the humoral immune response to infection by human immunodeficiency virus type 1. The third hypervariable region (V3 loop) is the principal neutralizing domain and is the primary target of neutralizing antibodies directed against the envelope proteins of HIV-1. The V3 loop is also the major determinant for HIV-1 cell-specific tropism. To further characterize the humoral immune response directed against the gp120 envelope proteins, we expressed two prototypic gp120 envelope proteins (LAI/HXB2 and ADA) and chimeric gp120 envelope proteins in stable transfected Drosophila melanogaster Schneider 2 cells. Sera from four infected adults over the course of infection [McNearney et al. (1992) Proc. natn. Acad. Sci. U.S.A. 89, p. 10,242] were assayed for reactivity with the respective envelope proteins. Sera obtained at early stages preferentially recognized the gp120 envelope protein ADA, whereas in later stages of infection the sera showed diminished reactivity with both gp120 LAI/HXB2 and gp120 ADA. Chimeric envelope proteins revealed that the humoral response was directed primarily against the V3 loop of gp120 ADA. Furthermore, 22 sera from HIV-1 infected individuals in different stages of the disease were tested. Reactivity of sera with the gp120 envelope protein ADA was seven-fold higher than with the gp120 envelope protein LAI/HXB2. Our results suggest that the humoral immune response is preferentially elicited against the V3 loop of the prototypic macrophage-tropic gp120 envelope protein ADA.

Adult↗
PubMed1995

Post-prandial lipaemia.

Post-prandial lipaemia represents the state of absorption during which TG metabolic capacity is under challenge. Low TG metabolic capacity imparts the risk of development of atherosclerosis. TG-intolerance has been shown to be an independent risk factor for CAD and impaired TG metabolic capacity could underlie a common high risk lipoprotein constellation of low HDL cholesterol and small sized HDL and LDL. Magnitude and duration of post-prandial lipaemia determine how much cholesterol is diverted from LDL and HDL into TG-rich lipoproteins through which it causes atherosclerosis. Potential means of intervention are improvement of TG metabolic capacity by reducing obesity, prescription of aerobic exercise, reduction of oxidizability of post-prandial lipoproteins by antioxidants and TG-lowering drugs.

Arteriosclerosis↗
PubMed1995

Postprandial state and atherosclerosis.

Accumulating evidence suggests that triglyceride-rich lipoproteins are an independent risk factor for atherosclerosis. This epidemiological evidence first emerged as a result of studying postprandial lipaemia that characterized the metabolic capacity of triglycerides in the postabsorptive state, that is, under challenge. Studies of postprandial lipaemia were helpful to explain several effects of triglyceride-rich lipoproteins on cholesteryl-ester-rich lipoproteins. From these studies it became apparent that peculiarities of cholesteryl-ester-rich lipoproteins, such as small LDL and small HDL, which have been associated with risk for atherosclerosis, were caused by impaired triglyceride metabolism.

Arteries↗
PubMed1995

Exercise and postprandial lipaemia.

Postprandial hyperlipidaemia is a risk factor for atherosclerosis in multiple vascular beds, independently of high-density lipoprotein (HDL) cholesterol. An increased level of HDL cholesterol is a strong indicator of a low risk of atherosclerosis. Exercise decreases postprandial lipaemia and, in turn, increases levels of HDL cholesterol. The favourable effects of exercise on lipoprotein metabolism, particularly evident in the postprandial state, may thus help to decrease susceptibility to atherosclerosis in exercise-trained people.

Arteriosclerosis↗
PubMed1995

[Effectiveness, tolerance and safety of simvastatin in comparison with bezafibrate in treatment of hypercholesterolemia].

The efficacy, tolerability and safety of simvastatin was compared to that of bezafibrate in a randomized placebo controlled double-blind trial including 64 patients with primary hypercholesterolemia with total cholesterol levels above 240 mg/dl and low-density lipoprotein (LDL) cholesterol above 195 mg/dl. During a placebo period of four weeks patients were counselled for a diet low in cholesterol (< 300 mg/day) and saturated fat (< 10% of calories). This period was also used for randomization of the individuals into the bezafibrate and simvastatin group, respectively. Patients assigned to bezafibrate treatment took bezafibrate at 600 mg/day throughout the entire 12 weeks of active treatment. Patients assigned to simvastatin took simvastatin at 10 mg/day when LDL-cholesterol was below 195 mg/dl, and at 20 mg/day when LDL-cholesterol was above 195 mg. To compare the lipid lowering effect of both substances total cholesterol, LDL- and high-density lipoprotein (HDL)-cholesterol were measured as well as triglycerides, very low density lipoprotein (VLDL)-cholesterol and the concentrations of apolipoproteins (apo)-AI, apo-AII and apo-B, respectively. These variables were compared between the two study groups with respect to the percentage change from baseline levels obtained during the placebo period. After a 12 week treatment period mean percent reduction of total cholesterol in the simvastatin group was 24% and that of LDL-cholesterol was 36%, both more pronounced than the respective reductions (14% and 17%) observed in the bezafibrate group. The mean percent increase in HDL-cholesterol was similar in both treatment groups (simvastation by 20% vs. bezafibrate by 17%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Effect of pancreas transplantation on lipoprotein lipase, postprandial lipemia, and HDL cholesterol.

Pancreas transplantation with systemic venous drainage of the graft causes elevated plasma levels of insulin, known to be a potent regulator of plasma lipoprotein metabolism. We studied 11 post-type I diabetic pancreas-kidney transplant recipients, 9 type I diabetic kidney transplant recipients displaying peripheral hyperinsulinemia due to subcutaneous insulin treatment, 11 nondiabetic kidney transplant recipients as controls for the effects of immunosuppressive medication, and 11 healthy control subjects, all matched for age, sex, and body mass index. We determined fasting lipids, lipoproteins and lipolytic enzymes, as well as postprandial lipid metabolism after a standardized oral fat load. High-density lipoprotein (HDL) cholesterol averaged 1.98 (0.40) mmol/L in pancreas-kidney transplant patients, clearly higher than that of kidney transplant recipients (1.52 (0.36) mmol/L, P < 0.05) or of controls (1.50 (0.38) mmol/L, P < 0.05). In pancreas-kidney transplant patients postprandial lipemia was lowest and lipoprotein lipase activity was highest (average 32% and 154%, respectively, of the mean of the controls) compared with nondiabetic kidney transplant recipients (P < 0.005, P < 0.05) and healthy controls (P < 0.001, P < 0.01). In type I diabetic kidney transplant recipients the levels of HDL cholesterol (1.88 (0.63) mmol/L), postprandial lipemia, and lipoprotein lipase activity were intermediate between pancreas-kidney transplant patients and healthy controls. The distinctly elevated HDL cholesterol in pancreas-kidney transplant patients can be readily explained by the low postprandial triglyceride levels resulting from a high activity of lipoprotein lipase. The very favorable lipid profile in post-diabetic pancreas-kidney transplant recipients could be expected to counteract the severe atherosclerotic risk of long-standing diabetes.

Adult↗
PubMed1994

Fenofibrate improves postprandial chylomicron clearance in II B hyperlipoproteinemia.

In 11 patients with IIB hyperlipoproteinemia we studied fasting lipids, lipoproteins, lipoprotein-modifying enzymes, and postprandial lipid metabolism after a standardized oral fat load supplemented with vitamin A before and 12 weeks after treatment with fenofibrate, a third-generation fibric acid derivative. Fasting plasma cholesterol, triglycerides, low-density lipoprotein cholesterol decreased significantly (P < 0.05, P < 0.01, P < 0.01), high-density lipoprotein subfraction 3 cholesterol increased significantly (P < 0.05), and high-density lipoprotein subfraction 2 cholesterol remained unchanged. Postprandial lipemia, i.e., the integrated postprandial triglyceride concentrations corrected for the fasting triglyceride level, and postprandial chylomicron concentrations, as assessed by biosynthetic labeling of chylomicrons with retinyl palmitate, decreased by 40.6% and 60.1% (P < 0.05; P < 0.05), respectively. The activity of lipoprotein lipase (LPL) increased by 33.6% (P < 0.05); the increase in LPL during fenofibrate treatment was positively correlated with the increase in high-density lipoprotein cholesterol (r = 0.84; P < 0.005). Hepatic lipase and cholesteryl ester transfer protein mass and activity remained unchanged. We conclude that lipid-lowering therapy with fenofibrate ameliorates fasting and, more profoundly, postprandial lipoprotein transport in hypertriglyceridemia by curbing postprandial triglyceride and chylomicron accumulation, at least in part, through an increase in LPL activity.

Adult↗
PubMed1994

The immunosuppressive substance 2-chloro-2-deoxyadenosine modulates lipoprotein metabolism in a murine macrophage cell line (P388 cells).

A recently developed immunosuppressive substance, 2-chloro-2-deoxyadenosine (2-CdA), was reported to inhibit monocyte functions at low concentration. Because macrophages play a key role in the formation of atherosclerotic plaques, it was of interest to study the effect of 2-CdA on cellular lipid metabolism. For this purpose we have used a macrophage cell line (P388) to perform incubation studies in the presence of acetylated low density lipoprotein (Ac-LDL) and 2-CdA. The addition of 2-CdA, in concentrations ranging from 5-20 nM, induced a dose-dependent decrease in cellular cholesterol content and in the amount of extracellular [14C]oleic acid (OA) incorporated into the cholesteryl ester (CE) fraction. The effect was maximized at 20 nM 2-CdA with an 86% reduction in cholesterol esterification compared to controls (P < 0.008). To evaluate the mechanism of interaction of 2-CdA with cellular lipid metabolism, deoxycytidine (dCyt) and 3-methoxybenzamide (3-MOB), substances known to antagonize the effect of 2-CdA in different ways, were co-administered with 2-CdA. dCyt, a competitive inhibitor of dCyt kinase, which catalyzes phosphorylation to the active metabolite, antagonized the effects of 20 nM 2-CdA, producing significantly greater incorporation of extracellular [14C]OA into the CE fraction than in the presence of 2-CdA alone (P < 0.0086). Co-incubation with 2-CdA and the poly-ADP-ribose synthetase inhibitor 3-MOB, which is known to render cells resistant to 2-CdA toxicity by preventing cellular nicotinamide adenine dinucleotide (NAD)- and adenosine triphosphase-depletion, also reversed the effect of 2-CdA on lipid accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗
PubMed1994

Triglyceride-rich lipoproteins and atherosclerosis.

Plasma triglyceride (TG)-rich lipoproteins are related to high density lipoprotein (HDL)-cholesterol and risk of coronary artery disease (CAD). Two major hypotheses on the role of HDL in the development of CAD have been proposed: a 'causalist' view assigns a protective effect against atherosclerosis to HDL and a 'non-causalist' view states that HDL do not interfere directly with development of atheroma but reflect metabolism of TG-rich lipoproteins. HDL exist as two major subfractions: small, lipid-poor, dense HDL3, and larger, lipid-rich, less dense HDL2, with variable levels of total-HDL cholesterol. Rapid lipolysis of TG-rich lipoproteins produces increased lipid uptake, formation of HDL2 and may protect the arterial wall; delayed lipolysis increases transfer of TG from TG-rich lipoproteins into HDL. Cholesteryl ester transfer protein (CETP) catalyzes lipid exchange and may be the mechanism for switching 'good cholesterol' into 'bad cholesterol'. According to this view, the driving force for the switch is the metabolism of TG-rich lipoproteins. Rapid clearance of TG-rich lipoproteins promotes formation of HDL2, low levels of TG-rich lipoproteins prevent transfer of HDL-cholesteryl esters into TG-rich lipoproteins keeping HDL-cholesterol high. The net effect is antiatherogenic. Accumulation of TG-rich lipoproteins leads to transfer of cholesteryl esters from HDL into lipoprotein fractions associated with high CAD risk.

Cholesterol, HDL↗