Hyperlipidemias: van Dijk KW

Rensen PC, van Dijk KW, Havekes LM. · No affiliation provided · Arterioscler Thromb Vasc Biol. · Pubmed #16306435 links to  free full text

This publication has no abstract.

DeRuiter MC, Alkemade FE, Gittenberger-de Groot AC, Poelmann RE, Havekes LM, van Dijk KW. · Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands. · Curr Opin Lipidol. · Pubmed #18607178 No free full text.

Abstract: PURPOSE OF REVIEW: In the last 20 years, an increasing amount of epidemiological and pathological evidence has become available illustrating the relationship between an adverse in-utero environment and increased risk of vascular disease in the offspring. It is now generally accepted that epigenetic phenomena, such as either DNA methylation or chromatin modifications or both mediate the long-term memory and thus developmental programming of cells and tissues. RECENT FINDINGS: In utero, the placenta and fetus are exposed to the metabolic, antioxidant and pro-inflammatory and anti-inflammatory signals from the mother and will likely respond specifically. In the fetus, these responses may lead to permanent changes either in DNA methylation or chromatin modification or both and these changes may lead to increased atherosclerosis susceptibility in adulthood. However, the molecular mechanisms responsible for the translation of an adverse maternal environment into permanent epigenetic changes are poorly understood. SUMMARY: In this review, we briefly summarize the possible signals crossing the placental barrier and discuss the molecular mechanisms of epigenetic programming in the developing fetus leading to increased athero-susceptibility of the vessel wall.

van Dijk KW, Rensen PC, Voshol PJ, Havekes LM. · Department of Human Genetics, Leiden University Medical Center, PO Box 9503, 2000 RA Leiden, The Netherlands. · Curr Opin Lipidol. · Pubmed #15166778 No free full text.

Abstract: PURPOSE OF REVIEW: Apolipoprotein (apo)CIII and apoAV play an important role in triglyceride metabolism as evidenced by the unambiguous and opposing phenotypes of transgenic and knockout mouse models. In this review we discuss studies on the genetics, protein structure, and regulation of apoCIII and apoAV and compare their potential molecular mechanisms of action in triglyceride metabolism. We examine the hypothesis that apoCIII and apoAV synergistically affect triglyceride metabolism. RECENT FINDINGS: It has now been firmly established that variation in plasma triglyceride levels in a wide range of human populations is strongly associated with genetic variation at the chromosomal locus encoding both the APOC3 and APOA5 genes, the APOA1/C3/A4/A5 gene cluster. The close physical linkage of these genes and the frequent concurrence of genetic variants, however, complicate the assignment of specific metabolic defects to specific polymorphisms. Recent insight into the regulation of APOC3 and APOA5 gene expression and structural modeling studies on the apoAV protein have provided novel clues for the potential molecular mechanisms responsible for the effects of apoCIII and apoAV on triglyceride metabolism. SUMMARY: Hypertriglyceridemia is a major independent risk factor in the development of cardiovascular disease. Moreover, triglyceride-derived fatty acids are thought to play a key role in the development and progression of the metabolic syndrome. As modulators of triglyceride metabolism, apoCIII and apoAV are key players and potential therapeutic targets. However, little is known of their molecular mechanism and potential cooperativity. Rational therapeutic application will require the filling of this hiatus in our knowledge.

Gerritsen G, van der Hoogt CC, Schaap FG, Voshol PJ, Kypreos KE, Maeda N, Groen AK, Havekes LM, Rensen PC, van Dijk KW. · Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. · J Lipid Res. · Pubmed #18263930 links to  free full text

Abstract: Apolipoprotein E2 (apoE2)-associated hyperlipidemia is characterized by a disturbed clearance of apoE2-enriched VLDL remnants. Because excess apoE2 inhibits LPL-mediated triglyceride (TG) hydrolysis in vitro, we investigated whether direct or indirect stimulation of LPL activity in vivo reduces the apoE2-associated hypertriglyceridemia. Here, we studied the role of LPL and two potent modifiers, the LPL inhibitor apoC-III and the LPL activator apoA-V, in APOE2-knockin (APOE2) mice. Injection of heparin in APOE2 mice reduced plasma TG by 53% and plasma total cholesterol (TC) by 18%. Adenovirus-mediated overexpression of LPL reduced plasma TG by 85% and TC by 40%. Both experiments indicate that the TG in apoE2-enriched particles is a suitable substrate for LPL. Indirect activation of LPL activity via deletion of Apoc3 in APOE2 mice did not affect plasma TG levels, whereas overexpression of Apoa5 in APOE2 mice did reduce plasma TG by 81% and plasma TC by 41%. In conclusion, the hypertriglyceridemia in APOE2 mice can be ameliorated by the direct activation of LPL activity. Indirect activation of LPL via overexpression of apoA-V does, whereas deletion of apoC-III does not, affect the plasma TGs in APOE2 mice. These data indicate that changes in apoA-V levels have a dominant effect over changes in apoC-III levels in the improvement of APOE2-associated hypertriglyceridemia.

Rip J, van Dijk KW, Sierts JA, Kastelein JJ, Twisk J, Kuivenhoven JA. · Academic Medical Center, Department of Vascular Medicine, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. · Biochim Biophys Acta. · Pubmed #16990047 No free full text.

Abstract: Intramuscular (IM) application of adeno-associated virus serotype 1 (AAV1) for the delivery of human lipoprotein lipase (hLPL) was previously shown efficacious in mice with chylomicronemia. The current study addresses whether AAV1-LPL(S447X) can reduce elevated triglyceride (TG) levels in mice with attenuated clearance of TG-rich remnant particles. METHODS: Female mice, expressing human apoE2 but deficient for endogenous apoE (apoE2KI) received IM injections of AAV1-LPL(S447X) (n=6; 8 x 10(12) gc/kg; 4-sites) or PBS (n=5). Following lipid monitoring, the mice were challenged with intravenous Intralipid injections, and sacrificed 3 months after treatment. RESULTS: In the mice that received LPL gene therapy, a marked increase of post-heparin hLPL protein levels (averaging 517+/-277 ng/mL vs. 4+/-3 ng/mL in apoE2KI-untreated) induced 20% reductions of fasting plasma TG levels (p<0.05). This was accompanied by two-fold increased TG clearance rates after Intralipid administration at 6 weeks after treatment (p<0.05). Post-mortem analyses revealed increased levels of TG (2-fold, p<0.005) and cholesterol (1.7-fold, p<0.001) in the treated muscles. CONCLUSIONS: IM application of AAV1-LPL(S447X) is effective in reducing TG levels in a mouse model for type III dyslipidemia. Thus, hypertriglyceridemia caused by attenuated uptake of TG-rich lipoproteins can be alleviated by increasing lipolytic function of the skeletal muscle tissue.

Henneman P, Schaap FG, Havekes LM, Rensen PC, Frants RR, van Tol A, Hattori H, Smelt AH, van Dijk KW. · Department of Human Genetics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. · Atherosclerosis. · Pubmed #16777114 No free full text.

Abstract: OBJECTIVE: The recently discovered apoAV is hypothesized to affect triglyceride metabolism by stimulating the lipolysis of triglycerides in VLDL and chylomicrons. We set out to determine the association between increased serum TG levels, plasma apoAV levels, and polymorphism of the APOA5 gene, with specific emphasis on the APOA5 S19W variation. This mutation alters the endoplasmic reticulum signal peptide and is hypothesized to impair apoAV secretion into the circulation. METHODS AND RESULTS: Two haplotype-tagging APOA5 polymorphisms, APOA5 S19W and APOA5 -1131T>C and plasma apoAV levels were determined in a population of patients with severe hypertriglyceridemia (HTG). As compared to a random control population, the allele frequencies of the APOA5 S19W and -1131T>C rare variants were significantly increased in HTG patients. Furthermore, the HTG population exhibited markedly elevated plasma apoAV levels that were positively correlated with serum TG levels. Plasma apoAV levels were positively correlated with occurrence of the APOA5 S19W rare variant. CONCLUSIONS: The increased allele frequencies of the APOA5 S19W and -1131T>C rare variants in the HTG population are in agreement with previous reports. Our data show a positive correlation between apoAV and TG levels. Moreover the finding of a positive association between apoAV levels and the APOA5 S19W rare variant is in disagreement with the hypothesis that this variant is poorly secreted.

van der Hoogt CC, Berbée JF, Espirito Santo SM, Gerritsen G, Krom YD, van der Zee A, Havekes LM, van Dijk KW, Rensen PC. · The Netherlands Organization for Applied Scientific Research-Quality of Life, Gaubius Laboratory, P.O. Box 2215, 2301 CE Leiden, The Netherlands. · Biochim Biophys Acta. · Pubmed #16478678 No free full text.

Abstract: We have recently shown that the predominant hypertriglyceridemia in human apolipoprotein C1 (APOC1) transgenic mice is mainly explained by apoCI-mediated inhibition of the lipoprotein lipase (LPL)-dependent triglyceride (TG)-hydrolysis pathway. Since the very-low-density lipoprotein receptor (VLDLr) and apoCIII are potent modifiers of LPL activity, our current aim was to study whether the lipolysis-inhibiting action of apoCI would be dependent on the presence of the VLDLr and apoCIII in vivo. Hereto, we employed liver-specific expression of human apoCI by using a novel recombinant adenovirus (AdAPOC1). In wild-type mice, moderate apoCI expression leading to plasma human apoCI levels of 12-33 mg/dl dose-dependently and specifically increased plasma TG (up to 6.6-fold, P < 0.001), yielding the same hypertriglyceridemic phenotype as observed in human APOC1 transgenic mice. AdAPOC1 still increased plasma TG in vldlr(-/-) mice (4.1-fold, P < 0.001) and in apoc3(-/-) mice (6.8-fold, P < 0.001) that were also deficient for the low-density lipoprotein receptor (LDLr) and LDLr-related protein (LRP) or apoE, respectively. Thus, irrespective of receptor-mediated remnant clearance by the liver, liver-specific expression of human apoCI causes hypertriglyceridemia in the absence of the VLDLr and apoCIII. We conclude that apoCI is a powerful and direct inhibitor of LPL activity independent of the VLDLr and apoCIII.

Kypreos KE, van Dijk KW, Havekes LM, Zannis VI. · Molecular Genetics, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA. · J Biol Chem. · Pubmed #15576362 links to  free full text

Abstract: To identify the residues in the carboxyl-terminal region 260-299 of human apolipoprotein E (apoE) that contribute to hypertriglyceridemia, two sets of conserved, hydrophobic amino acids between residues 261 and 283 were mutated to alanines, and recombinant adenoviruses expressing these apoE mutants were generated. Adenovirus-mediated gene transfer of apoE4-mut1 (apoE4 (L261A, W264A, F265A, L268A, V269A)) in apoE-deficient mice (apoE(-/-)) corrected plasma cholesterol levels and did not cause hypertriglyceridemia. In contrast, gene transfer of apoE4-mut2 (apoE4 (W276A, L279A, V280A, V283A)) did not correct hypercholesterolemia and induced mild hypertriglyceridemia. ApoE-induced hyperlipidemia was corrected by co-infection with a recombinant adenovirus expressing human lipoprotein lipase. Both apoE4 mutants caused only a small increase in hepatic very low density lipoprotein-triglyceride secretion. Density gradient ultracentrifugation analysis of plasma and electron microscopy showed that wild-type apoE4 and apoE4-mut2 displaced apoA-I from the high density lipoprotein (HDL) region and promoted the formation of discoidal HDL, whereas the apoE4-mut1 did not displace apoA-I from HDL and promoted the formation of spherical HDL. The findings indicate that residues Leu-261, Trp-264, Phe-265, Leu-268, and Val-269 of apoE are responsible for hypertriglyceridemia and also interfere with the formation of HDL. Substitutions of these residues by alanine provide a recombinant apoE form with improved biological functions.

Kypreos KE, Li X, van Dijk KW, Havekes LM, Zannis VI. · Molecular Genetics, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118-2394, USA. · Biochemistry. · Pubmed #12924933 No free full text.

Abstract: Apolipoprotein E2, which has an R158 for C substitution, has reduced affinity for the LDL receptor and is associated with type III hyperlipoproteinemia in humans. Consistent with these observations, we have found that following adenovirus-mediated gene transfer, full-length apoE2 aggravates the hypercholesterolemia and induces hypertriglyceridemia in E-deficient mice and induces combined hyperlipidemia in C57BL/6 mice. Unexpectedly, the truncated apoE2-202 form that has an R158 for C substitution when expressed at levels similar to those of the full-length apoE2 normalized the cholesterol levels of E-deficient mice without induction of hypertriglyceridemia. The apoE2 truncation increased the affinity of POPC-apoE particles for the LDL receptor, and the full-length apoE2 had a dominant effect in VLDL triglyceride secretion. Hyperlipidemia in normal C57BL/6 mice was prevented by coinfection with equal doses of each, the apoE2 and the apoE2-202-expressing adenoviruses, indicating that truncated apoE forms have a dominant effect in remnant clearance. Hypertriglyceridemia was completely corrected by coinfection of mice with an adenovirus-expressing wild-type lipoprotein lipase, whereas an inactive lipoprotein lipase had a smaller effect. The findings suggest that the apoE2-induced dyslipidemia is not merely the result of substitution of R158 for C but results from increased secretion of a triglyceride-enriched VLDL that cannot undergo lipolysis, inhibition of LpL activity, and impaired clearance of chylomicron remnants. Infection of E(-)(/)(-)xLDLr(-)(/)(-) double-deficient mice with apoE2-202 did not affect the plasma cholesterol levels, and also did not induce hypertriglyceridemia. In contrast, apoE2 exacerbated the hypercholesterolemia and induced hypertriglyceridemia, suggesting that the LDL receptor is the predominant receptor in remnant clearance.

Gerritsen G, Kypreos KE, van der Zee A, Teusink B, Zannis VI, Havekes LM, van Dijk KW. · Department of Human Genetics, Leiden University Medical Center, The Netherlands. · J Lipid Res. · Pubmed #12576523 links to  free full text

Abstract: Familial dysbetalipoproteinemia associated with the apolipoprotein E2 (APOE2) genotype is a recessive disorder with low penetrance. We have investigated whether additional expression of full-length APOE3, APOE4, or a truncated variant of APOE4 (APOE4-202) can reduce APOE2- associated hyperlipidemia. This was achieved using adenovirus-mediated gene transfer to mice transgenic for human APOE2 and deficient for endogenous Apoe (APOE2.Apoe-/- mice). The hyperlipidemia of APOE2.Apoe-/- mice was readily aggravated by APOE3 and APOE4 overexpression. Only a very low dose of APOE4 adenovirus was capable of reducing the serum cholesterol and triglyceride (TG) levels. Expression of higher doses of APOE4 was associated with an increased VLDL-TG production rate and the accumulation of TG-rich VLDL in the circulation. In contrast, a high dose of adenovirus carrying APOE4-202 reduced both the cholesterol and TG levels in APOE2.Apoe-/- mice. Despite the absence of the C-terminal lipid-binding domain, APOE4-202 is apparently capable of binding to lipoproteins and mediating hepatic uptake. Moreover, overexpression of APOE4-202 in APOE2.Apoe-/- mice does not aggravate their hypertriglyceridemia. These results extend our previous analyses of APOE4-202 expression in Apoe-/- mice and demonstrate that apoE4-202 functions even in the presence of clearance-defective apoE2. Thus, apoE4-202 is a safe and efficient candidate for future therapeutic applications.

Kypreos KE, Morani P, van Dijk KW, Havekes LM, Zannis VI. · Whitaker Cardiovascular Institute, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118-2394, USA. · Biochemistry. · Pubmed #11352738 No free full text.

Abstract: Apolipoprotein E (apoE) promotes receptor-mediated catabolism of apoE-containing lipoprotein remnants. Impairments in remnant clearance are associated with type III hyperlipoproteinemia and premature atherosclerosis. In humans, apoE plasma levels correlate with plasma triglyceride levels, suggesting that excess apoE may also affect plasma triglyceride levels. We have used adenovirus-mediated gene transfer in mice to map the domains of apoE required for cholesterol and triglyceride clearance, in vivo. Adenovirus expressing apoE3 and apoE4 at doses of (1-2) x 10(9) pfu increased plasma cholesterol and triglyceride levels in normal C57BL6 mice and failed to normalize the high cholesterol levels of apoE-deficient mice due to induction of hypertriglyceridemia. In contrast, an adenovirus expressing the truncated apoE 1-185 form normalized the cholesterol levels of E(-)(/)(-) mice and did not cause hypertriglyceridemia. Northern blot analysis of hepatic RNA from mice expressing the full-length and the truncated apoE forms showed comparable steady-state apoE mRNA levels of the full-length apoE forms that cause hyperlipidemia and the truncated apoE forms that do not cause hyperlipidemia. The findings suggest that the amino-terminal residues 1-185 of apoE are sufficient for the clearance of apoE-containing lipoprotein remnants by the liver, whereas domains of the carboxy-terminal one-third of apoE are required for apoE-induced hyperlipidemia.

de Beer F, van Dijk KW, Jong MC, van Vark LC, van der Zee A, Hofker MH, Fallaux FJ, Hoeben RC, Smelt AH, Havekes LM. · TNO-Prevention and Health, Gaubius Laboratory, Leiden, the Netherlands. · Arterioscler Thromb Vasc Biol. · Pubmed #10894820 links to  free full text

Abstract: The apolipoprotein E2 (Lys146-->Gln) variant is associated with a dominant form of familial dysbetalipoproteinemia. Heterozygous carriers of this variant have elevated levels of plasma triglycerides, cholesterol, and apolipoprotein E (apoE). It was hypothesized that the high amounts of triglycerides in the very low density lipoprotein (VLDL) fraction are due to a disturbed lipolysis of VLDL. To test this hypothesis, apoE knockout mice were injected with an adenovirus containing the human APOE*2 (Lys146-->Gln) gene, Ad-E2(146), under the control of the cytomegalovirus promoter. ApoE knockout mice injected with an adenovirus vector encoding human apoE3 (Ad-E3) were used as controls. Five days after adenovirus injection, plasma cholesterol levels of mice injected with a high dose of Ad-E2(146) (2x10(9) plaque-forming units) were not changed compared with preinjection levels, whereas in the group who received a low dose of Ad-E2(146) (5x10(8) plaque-forming units) and in the groups injected with a low or a high dose of Ad-E3, plasma cholesterol levels were decreased 5-, 6-, and 12-fold, respectively. Plasma triglycerides were not affected in mice injected with Ad-E3. In contrast, a 7-fold increase in plasma triglycerides was observed in mice injected with the low dose of Ad-E2(146) compared with mice injected with Ad-E3. Injection with the high dose of Ad-E2(146) resulted in a dramatic increase of plasma triglycerides (50-fold compared with Ad-E3 injection). In vitro lipolysis experiments showed that the lipolysis rate of VLDLs containing normal amounts of apoE2 (Lys146-->Gln) was decreased by 54% compared with that of VLDLs containing comparable amounts of apoE3. The in vivo VLDL-triglyceride production rate of Ad-E2(146)-injected mice was not significantly different from that of Ad-E3-injected mice. These results demonstrate that expression of apoE2 (Lys146-->Gln) causes hypertriglyceridemia due to an apoE variant-specific inhibition of the hydrolysis of VLDL-triglycerides.

van Dijk KW, van Vlijmen BJ, de Winther MP, van 't Hof B, van der Zee A, van der Boom H, Havekes LM, Hofker MH. · Department of Human Genetics, Leiden University Medical Center, The Netherlands. · Arterioscler Thromb Vasc Biol. · Pubmed #10591674 links to  free full text

Abstract: To investigate the relative roles of the LDL receptor- and non-LDL receptor-mediated pathways in the clearance of apolipoprotein E (apoE) variants in vivo, we have generated apoE2(Arg(158)-Cys) (apoE2) and apoE3-Leiden transgenic mice deficient for the endogenous mouse Apoe and Ldl receptor genes (Apoe-/-.Ldlr-/- mice). Unexpectedly, on the Apoe-/-.Ldlr-/- background, expression of neither apoE2 nor apoE3-Leiden results in a decrease of the hyperlipidemia. In contrast, serum cholesterol levels are increased by the introduction of apoE2 and apoE3-Leiden in Apoe-/-.Ldlr-/- mice (to 39.1+/-7.1 and 37.6+/-7.6 mmol/L, respectively, from 25. 9+/-6.5 mmol/L). In addition, in these transgenic mice, the serum triglyceride levels are substantially increased (to 9.6+/-7.0 and 5. 8+/-2.8 mmol/L, respectively, from 0.7+/-0.5 mmol/L), which is associated with a decreased efficiency of in vitro LPL-mediated lipolysis of circulating VLDL. The VLDL-triglyceride secretion rate is not affected by the expression of apoE2 or apoE3-Leiden on the Apoe-/-.Ldlr-/- background. These results indicate that in the absence of the LDL receptor, clearance of triglyceride-rich apoE2 and apoE3-Leiden-containing lipoproteins via alternative hepatic receptors, such as the LDL receptor-related protein (LRP) is inefficient. Although apoE2 and apoE3-Leiden are disturbed in binding to the LDL receptor in vitro, expression of 1 or 2 mouse Ldlr alleles in an apoE2.Apoe-/- or apoE3-Leiden.Apoe-/- background results in a gene dose-dependent decrease of the hyperlipidemia. Furthermore, overexpression of the LDL receptor via adenovirus-mediated gene transfer rescues the hyperlipidemia associated with apoE2 and apoE3-Leiden expression. These data indicate that in apoE2 and apoE3-Leiden transgenic mice, the LDL receptor constitutes the predominant route for clearance of VLDL remnants, carrying even poorly binding apoE variants, and that this pathway is functional despite an apoE-mediated disturbance in VLDL triglyceride lipolysis.

Jong MC, van Dijk KW, Dahlmans VE, Van der Boom H, Kobayashi K, Oka K, Siest G, Chan L, Hofker MH, Havekes LM. · TNO-Prevention and Health, Gaubius Laboratory, 2301 CE Leiden, The Netherlands. · Biochem J. · Pubmed #10024503 links to  free full text

Abstract: We have shown previously that human apolipoprotein (apo)C1 transgenic mice exhibit hyperlipidaemia, due primarily to an impaired clearance of very-low-density lipoprotein (VLDL) particles from the circulation. In the absence of at least the low-density-lipoprotein receptor (LDLR), it was shown that APOC1 overexpression in transgenic mice inhibited the hepatic uptake of VLDL via the LDLR-related protein. In the present study, we have now examined the effect of apoC1 on the binding of lipoproteins to both the VLDL receptor (VLDLR) and the LDLR. The binding specificity of the VLDLR and LDLR for apoC1-enriched lipoprotein particles was examined in vivo through adenovirus-mediated gene transfer of the VLDLR and the LDLR [giving rise to adenovirus-containing (Ad)-VLDLR and Ad-LDLR respectively] in APOC1 transgenic mice, LDLR-deficient (LDLR-/-) mice and wild-type mice. Remarkably, Ad-VLDLR treatment did not reduce hyperlipidaemia in transgenic mice overexpressing human APOC1, irrespective of both the level of transgenic expression and the presence of the LDLR, whereas Ad-VLDLR treatment did reverse hyperlipidaemia in LDLR-/- and wild-type mice. On the other hand, Ad-LDLR treatment strongly decreased plasma lipid levels in these APOC1 transgenic mice. These results suggest that apoC1 inhibits the clearance of lipoprotein particles via the VLDLR, but not via the LDLR. This hypothesis is corroborated by in vitro binding studies. Chinese hamster ovary (CHO) cells expressing the VLDLR (CHO-VLDLR) or LDLR (CHO-LDLR) bound less APOC1 transgenic VLDL than wild-type VLDL. Intriguingly, however, enrichment with apoE enhanced dose-dependently the binding of wild-type VLDL to CHO-VLDLR cells (up to 5-fold), whereas apoE did not enhance the binding of APOC1 transgenic VLDL to these cells. In contrast, for binding to CHO-LDLR cells, both wild-type and APOC1 transgenic VLDL were stimulated upon enrichment with apoE. From these studies, we conclude that apoC1 specifically inhibits the apoE-mediated binding of triacylglycerol-rich lipoprotein particles to the VLDLR, whereas apoC1-enriched lipoproteins can still bind to the LDLR. The variability in specificity of these lipoprotein receptors for apoC1-containing lipoprotein particles provides further evidence for a regulatory role of apoC1 in the delivery of lipoprotein constituents to different tissues on which these receptors are located.

Henneman P, Schaap FG, Rensen PC, van Dijk KW, Smelt AH. · No affiliation provided · J Intern Med. · Pubmed #18088255 No free full text.

This publication has no abstract.