HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Escolà-Gil, J. C. Articles by Blanco-Vaca, F. Search for Related Content PubMed PubMed Citation Articles by Escolà-Gil, J. C. Articles by Blanco-Vaca, F. Social Bookmarking                      What's this?

The Journal of Lipid Research, Vol. 39, 457-462, February 1998
Copyright © 1998 by Lipid Research, Inc.

Rapid Communication

Human apolipoprotein A-II is a pro-atherogenic molecule when it is expressed in transgenic mice at a level similar to that in humans: evidence of a potentially relevant species-specific interaction with diet

Correspondence to: Francisco Blanco-Vaca.

	ABSTRACT

TOP ABSTRACT INTRODUCTION METHODS RESULTS AND DISCUSSION REFERENCES

We report on the effect of human apolipoprotein (apo) A-II transgene expression on atherosclerosis susceptibility in two transgenic lines (25.3 and 11.1) whose plasma human apoA-II concentrations (~23 and 96 mg/dl, respectively) span the normal range in humans. After 9 months of an atherogenic diet, 25.3 and 11.1 transgenic mice developed aortic atherosclerotic lesions that were ~1.7- and 7-fold, respectively, more extensive than those of nontransgenic control mice. However, there was no difference in the area of atherosclerosis of transgenic and control mice when fed a regular chow diet. This contrasts with the findings in murine apoA-II transgenic mice and provides evidence of a species-specific characteristic that could be of relevance with respect to the high fat intake diets common in most industrialized countries. A possible mechanism of the pro-atherogenic action of human apoA-II could be the inhibition of reverse cholesterol transport and, in support of this, we observed an impairment of apoA-I-HDL particle interconversion in the plasma of 11.1 transgenic mice caused, at least in part, by a marked decrease in the endogenous lecithin:cholesterol acyltransferase activity.—Escolà-Gil, J. C., À. Marzal-Casacuberta, J. Julve-Gil, B. Y. Ishida, J. Ordóñez-Llanos, L. Chan, F. González-Sastre, and F. Blanco-Vaca. Human apolipoprotein A-II is a pro-atherogenic molecule when it is expressed in transgenic mice at a level similar to that in humans: evidence of a potentially relevant species-specific interaction with diet. J. Lipid Res. 1998. 39: 457–462.

Supplementary key words: high density lipoproteins, atherosclerosis, apolipoprotein A-I, lecithin:cholesterol acyltransferase

	INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS AND DISCUSSION REFERENCES

High density lipoprotein cholesterol (HDLc) is inversely related to the risk of atherosclerosis in humans (1). However, not all individuals with HDLc deficiency have the expected cardiovascular risk and the mechanisms by which HDL modulates atherosclerosis susceptibility are poorly defined (1). HDL particles are classified (2) according to the content of their major apolipoproteins (apos), apoA-I and apoA-II. Different classes of HDL may have differential protective effects against atherosclerosis, but clinical studies addressing this issue have yielded conflicting results (1) (2). Genetic modification of experimental animals is a powerful way to dissect the contribution of specific gene products to disease (3). Results from such experiments leave little doubt concerning the anti-atherogenic role of human apoA-I (3) (4) (5). However, the role of human apoA-II in atherosclerosis remains poorly defined and controversial. Schultz et al. (4) showed that human apoA-II coexpression with human apoA-I in transgenic mice abrogated the anti-atherogenic effects of apoA-I, whereas initial reports from two laboratories suggest that isolated expression of human apoA-II in mice confers a protective effect against atherosclerosis (5) (6). The observation that murine apoA-II transgenic mice are more prone to atherosclerosis than their littermate controls (7) (8) suggests that there are species differences in apoA-II action on atherogenesis. This seems feasible considering the structural and functional differences that exist between human and mouse apoA-II (4) (5) (7) (8) (9) (10) (11). An unusual characteristic of the stimulatory effect of murine apoA-II on atherosclerosis is that it is much more pronounced when animals are fed a regular chow diet than when fed a high fat, high cholesterol diet (7) (8). In this report we demonstrate that human apoA-II is, indeed, a pro-atherogenic molecule when it is expressed in mice at a level similar to that in humans (30–35 mg/dl), but only when the animals are fed a high fat, high cholesterol diet. Hence, even though the pro-atherogenic properties of apoA-II are a general characteristic of this molecule, there is a potentially relevant species-specific interaction between human apoA-II expression and diet.

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS AND DISCUSSION REFERENCES

Animals
Human apoA-II transgenic mice were developed by microinjection of a 3-kilobase base pair fragment of human genomic DNA into fertilized eggs of C57BL/6 mice (9). Of the three lines obtained, named 25.3, 21.5, and 11.1, we selected the 25.3 and 11.1 for study as their plasma human apoA-II concentrations span that of humans (9). Control and transgenic mice between 2 and 4 months of age were assigned to either an atherogenic diet or to a regular chow diet. After 9 months on the atherogenic diet, the mice that survived were killed. Because of the resistance to atherosclerosis of C57BL/6 mice when maintained on a regular chow diet (Purina mice diet 5001), this diet was extended up to 16 months. The high fat, high cholesterol (atherogenic) diet used (TD 88051 Harlan Teklad, Madison, WI) has the following composition: 75% mouse chow 5015, 7.5% cocoa butter, 1.25% cholesterol, 0.5% sodium cholate.

Quantification of atherosclerosis
Mice subjected to 9 months of an atherogenic diet were anesthetized and exsanguinated at 11–13 months of age. The hearts were removed, embedded in OCT compound (Tissue-Tek), and sectioned as previously described (12). Oil red O staining of lesion areas present in the proximal aorta were measured in each mouse in eight 10-µm sections interspaced by 40 µm measured with a calibrated eyepiece. The first section was taken 40 µm distal to the point placed between the end of the aortic sinus and the beginning of the aorta. In the case of fibroproliferative lesions, the area quantified included all lesions (from the lumen to the normal vessel wall) and not just the fatty portion. The quantification of atherosclerosis was performed blinded with respect to the origin of the specimens. Also, qualitative analyses were performed in all sections of the proximal aorta as previously published (13).

Determination of lipids, lipoproteins, apolipoproteins, and enzymes
Methodologies for measuring lipid, lipoprotein, and apolipoprotein concentrations as well as endogenous lecithin:cholesterol acyltransferase (LCAT) activity were as described (9) (14). Unlike human, mouse pre-heparin plasma contains high levels of hepatic lipase (HL) with a low affinity for heparin (15). The pre-heparin plasma HDL-triglyceride hydrolysis mediated by HL was measured as free [³H]oleate generated after incubation of a mixture of a pooled isolated [³H] triolein-HDL and the individual pre-heparin plasmas (15). The origin of the pool of radioactive HDL used in the mixtures was the same as that of the pre-heparin plasma (control mice, 25.3 or 11.1) analyzed. The radioactive:non-radioactive HDL ratio in the final mixture was usually about 1:3. Results are expressed as relative to total (radioactive plus non-radioactive) HDL-triglyceride. Electrophoretic mobility of mouse apoA-I in plasma was determined by Western blotting using specific polyclonal antibodies (9).

	RESULTS AND DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS AND DISCUSSION REFERENCES

The results of the studies in transgenic mice expressing plasma levels of human apoA-II similar to those in humans could be relevant to human pathophysiology because apoA-II production rate, rather than its catabolism, is the major factor determining the concentration of apoA-II and the distribution of apoA-I between HDL particles that do, or do not, contain the apoA-II component (16). Moreover, there is evidence that the rate of synthesis of apoA-II in humans may be, largely, under genetic control (17).

After an atherogenic diet, our human apoA-II (25.3 and 11.1) transgenic mice developed more extensive aortic atherosclerosis than control mice ( Figure 1a and 1b). The areas of proximal aortic atherosclerosis in the 25.3 and the 11.1 males were, respectively, 1.8-fold and 7.7-fold that of the control male mice (Figure 1a). The same comparison in females indicated an increase of the atherosclerosis area of 1.7-fold in 25.3 mice and 6.2-fold in 11.1 mice (Figure 1b). Hence, there is a clear apoA-II dose-dependent increase in atherosclerosis susceptibility in the transgenic mice. As with other studies in mice, the area of atherosclerosis was greater in females relative to males (7) (13). Representative examples of the lesions observed are presented in Figure 1 (panels c to h). The high mortality rate of mice in the course of the atherogenic diet is noteworthy (Figure 1a and Figure 1b). Although the precise cause of death in these animals is not known, the mortality rate of each group seems closely related to the area of aortic atherosclerosis (Figure 1i). The death of several of these mice was noticed quickly enough to allow the analyses of the aortas. Large and advanced atherosclerotic lesions were observed in these cases. Furthermore, a major accumulation of lipids was sometimes observed in the coronary arteries and, as such, myocardial infarction could well be the cause of mortality in these mice. A high mortality rate has been reported previously in mice fed an atherogenic diet who had occlusions of the coronary arteries (18).

View larger version (707K): [in this window] [in a new window]   Figure 1. Atherosclerosis in the proximal aorta of human apoA-II transgenic and control mice after 9 months of an atherogenic diet. a: Area of atherosclerosis (expressed per section) in males. b: Area of atherosclerosis in females. In a and b, results are expressed as mean ± SEM; *P < 0.05, **P < 0.001 compared to control mice (Mann-Whitney U test). The number of mice analyzed and the number of mice dead before the end of the 9-month period is also shown. c to j : Representative photomicrographs of proximal aortic sections of C57BL/6 mice. All sections were stained with Oil red O and counterstained with hematoxylin; all panels have the same magnification, scale bar = 100 µm. c: Flat early fatty streak type I lesions in aortic valve attachments of a male control. d: Type I lesion of a 25.3 transgenic male. e : Raised lesions in aortic valve attachments extending to the free aortic wall in a 11.1 transgenic male. f: Multilayered foam cell deposits in a type II lesion of a control female. g: Fibroproliferative type II lesion of a 25.3 transgenic female. h: Severe fibroproliferative lesion with a large calcification (arrow) (confirmed by von Kossa method) in the free aortic wall of a 11.1 transgenic female. i: Association between the mortality rate before the end of the 9-month period of atherogenic diet and the area of aortic atherosclerosis found in the mice that survived this period and, therefore, could be analyzed.

For more detailed comparison, the atherosclerotic lesions were classified in two types (type I are lesions confined to the aortic valves and type II lesions are those that extend to the free aortic wall) and further sub-grouped as flat, raised, and advanced (13). This analysis also demonstrated that transgenic mice developed more advanced atherosclerotic lesions than control mice (data not shown).

In contrast to the atherogenic diet-fed animals, there was no significant difference in the area of atherosclerotic lesion of either transgenic line compared to control mice when they were fed a regular chow diet. These areas, in µm²/section and expressed as mean ± SE, were: 283 ± 111 in control males (n = 5), 625 ± 196 in 25.3 male transgenic mice (n = 2), and 487 ± 233 in 11.1 male transgenic mice (n = 4). Area lesions of control females (n = 4), 25.3 transgenic females (n = 4), and 11.1 transgenic females (n = 4) were, respectively, 1110 ± 460, 209 ± 57, and 643 ± 460. The variable influence of human apoA-II transgenesis on atherosclerosis in both types of diet was not due to different human apoA-II plasma levels. None of these 23 mice died before the end of the diet period; suggesting, again, that mice mortality was directly related to atherosclerosis.

The (VLDL-cholesterol + LDL-cholesterol) ÷ HDLc ratio was lower in male transgenic mice than in controls fed an atherogenic diet; the ratio being higher in female transgenics than in controls of the same sex ( Table 1). However, the relative increase in the atherosclerotic lesion area of transgenic mice of either gender is similar in relation to their control littermates. It is noteworthy that the HDLc is either higher (in male 25.3 mice), or at least not different, in transgenic compared to control animals, indicating that the absolute HDLc did not play a significant role in determining atherogenicity in these animals. Therefore, at least part of the pro-atherogenic effect of the human apoA-II expression may be due to the different protein composition of HDL in transgenic mice (Table 1). If HDL with apoA-I is more anti-atherogenic than HDL with apoA-I and apoA-II, a higher proportion of the latter particles would be expected to be less protective (3) (4) (7) (8).

There are biologically plausible mechanisms to explain why the expression of human apoA-II in mice is pro-atherogenic. These mice, especially those of 11.1 line, may have an impaired reverse cholesterol transport. This transgenic line has a reduced LCAT endogenous activity and, conversely, an increased reactivity to HL (Table 1). LCAT and HL have opposite actions in the remodeling of HDL particles: LCAT induces formation of HDL from preß HDL, whereas HL action forms preßHDL from HDL (19). The possibility that 11.1 transgenic mice plasma had a sharp reduction in apoA-I-containing HDL was confirmed by Western blot analysis ( Figure 2). In contrast, mouse and human apoA-II could be detected in HDL of 11.1 mice concomitantly with a substantial lipid component as judged by Sudan Black B staining (data not shown). It is possible that LCAT was trapped within the HDL containing the human apoA-II because this apolipoprotein is a poor cofactor for the enzyme (9). The transfer of cholesterol from preßHDL to HDL was shown by Castro et al. (20) to be slower in human apoA-I/apoA-II than in apoA-I transgenic mice; correlating with a more efficient cholesterol efflux in the latter. However, the report dealt with transgenic mice fed a regular chow diet; a situation in which atherosclerosis does not develop. Formation of preßHDL migrating apoA-I in 11.1 transgenic mice plasma could also be increased as a result of its displacement from HDL by human apoA-II (9).

View larger version (71K): [in this window] [in a new window]   Figure 2. Western blot of plasmas obtained from mice after 9 months of an atherogenic diet, probed with polyclonal antibodies to mouse apoA-I. Lanes 1 and 2: 11.1 transgenic male and female mice; lanes 3 and 4: control male and female mice; lanes 5 and 6: 25.3 transgenic male and female mice.

Previously, murine apoA-II transgenic mice (especially when maintained on regular chow diet) were shown to have increased atherosclerosis susceptibility but in the context of increased concentrations of HDLc and HDL particle size elevation, which is the opposite to their human apoA-II transgenic counterparts (4) (5) (7) (8) (9) (10) (11). Taken together, these results strongly support the concept that the pro-atherogenic properties of apoA-II are a general characteristic of this molecule and are not directly related to the HDLc concentration. The mechanisms by which apoA-II expression may cause increased susceptibility to atherosclerosis also include the decrease of the HDL inhibition of LDL oxidative modification (8) and the induction of insulin resistance (21) (22).

In summary, transgenic mice expressing human apoA-II have a dose-related increase of atherosclerotic lesions but only when fed an atherogenic diet. This provides evidence of a species-specific interaction between the expression of human ApoA-II and an atherogenic diet which could be of considerable potential relevance as the high fat diets are a common occurrence in developed countries. If the findings of this study are confirmed, clarification of the mechanisms implicated will require detailed characterization of the effects of human apoA-II expression on reverse cholesterol transport, on protection of LDL modification, and on insulin sensitivity.

rapid communication

	ACKNOWLEDGMENTS

This study was supported by grants from Fondo de Investigaciones Sanitarias 94/1304 and Fundació d'Investigació Cardiovascular-Marató de TV3 (to F.B-V.), Promoción General del Conocimiento PB93/1269 and Comissionat per a Universitats i Recerca 1995-SGR-265 (to F.G-S.), and HL16512 from the National Institutes of Health (to L. C.). During this study J. C. E-G was a predoctoral fellow of the Ministerio de Educación y Cultura. À. M-C. was supported by the Comissionat per a Universitats i Recerca. Editorial assistance was by Dr. Peter R. Turner of t-SciMed (Reus, Spain).

Manuscript received September 22, 1997; and in revised form November 20, 1997.

Abbreviations: apo, apolipoprotein; HDL, high density lipoproteins; HDLc, high density lipoprotein cholesterol; HL, hepatic lipase; LCAT, lecithin:cholesterol acyltransferase; LDL, low density lipoproteins; VLDL, very low density lipoproteins

	REFERENCES

TOP ABSTRACT INTRODUCTION METHODS RESULTS AND DISCUSSION REFERENCES

1. Assmann, G., A. von Eckardstein, and H. Funke. 1993. High density lipoproteins, reverse transport of cholesterol, and coronary artery disease. Insights from mutations. Circulation. 87: III28–III34.

2. Fruchart, J. C., G. Ailhaud, and J. M. Bard. 1993. Heterogeneity of high density lipoprotein particles. Circulation. 87: III22–III27.

3. Breslow, J. L. 1996. Mouse models of atherosclerosis. Science. 272:685-688[Abstract].

4. Schultz, J. R., Verstuyft, J. G., Gong, E. L., Nichols, A. V., Rubin, E. M. 1993. Protein composition determines the anti-atherogenic properties of HDL in transgenic mice. Nature. 365:762-764[Medline].

5. Schultz, J. R., Rubin, E. M. 1994. The properties of HDL in genetically engineered mice. Curr. Opin. Lipidol. 5:126-137[Medline].

6. Hennuyer, N., Tailleux, A., Caillaud, J. M., Fruchart, J. C., Denèfle, P., Duverger, N., Fievet, C. 1997. Protective effect of human apoA-II overexpression on atherogenesis in transgenic mice. Atherosclerosis. 130:S35. (abstract).

7. Warden, C. H., Hedrick, C. C., Qiao, J-H., Castellani, L. W., Lusis, A. J. 1993. Atherosclerosis in transgenic mice overexpressing apolipoprotein A-II. Science. 261:469-471[Abstract/Free Full Text].

8. Castellani, L. W., Navab, M., Van Lenten, B. J., Hedrick, C. C., Hama, S. Y., Goto, A. M., Fogelman, A. M., Lusis, A. J. 1997. Overexpression of apolipoprotein A-II in transgenic mice converts high density lipoproteins to proinflamatory particles. J. Clin. Invest. 100:464-474[Medline].

9. Marzal-Casacuberta, À., Blanco-Vaca, F., Ishida, B. Y., Julve-Gil, J., Shen, J., Calvet-Márquez, S., González-Sastre, F., Chan, L. 1996. Functional lecithin:cholesterol acyltransferase deficiency and high density lipoprotein deficiency in transgenic mice overexpressing human apolipoprotein A-II. J. Biol. Chem. 271:6720-6728[Abstract/Free Full Text].

10. Gong, E. L., Stoltzfus, L. J., Brion, C. M., Murugesh, D., Rubin, E. M. 1996. Contrasting in vivo effects of murine and human apolipoprotein A-II. J. Biol. Chem. 271:5984-5987[Abstract/Free Full Text].

11. Hedrick, C. C., Castellani, L. W., Warden, C. H., Puppione, D. L., Lusis, A. J. 1993. Influence of mouse apolipoprotein A-II on plasma lipoproteins in transgenic mice. J. Biol. Chem. 268:20676-20682[Abstract/Free Full Text].

12. Paigen, B., Morrow, P. A., Holmes, D., Mitchell, D., Williams, R. A. 1987. Quantitative assessment of atherosclerotic lesions in mice. Atherosclerosis. 68:231-240[Medline].

13. Qiao, J-H., Xie, P-Z., Fishbein, M. C., Kreuzer, J., Drake, T. A., Demer, L. L., Lusis, A. J. 1994. Pathology of atheromatous lesions in inbred and genetically engineered mice. Arterioscler. Thromb. Vasc. Biol. 14:1480-1497[Abstract/Free Full Text].

14. Blanco-Vaca, F., Qu, S-J., Fiol, C., Fan, H-Z., Pao, Q., Marzal-Casacuberta, À., Albers, J. J., Hurtado, I., Gracia, V., Pintó, X., Martí, T., Pownall, H. J. 1997. Molecular basis of fish-eye disease in a patient from Spain. Characterization of a novel mutation in the LCAT gene and lipid analysis of the cornea. Arterioscler. Thromb. Vasc. Biol. 17:1382-1391[Abstract/Free Full Text].

15. Peterson, J., Bengtsson-Olivecrona, G., Olivecrona, T. 1986. Mouse preheparin plasma contains high levels of hepatic lipase with low affinity for heparin. Biochim. Biophys. Acta. 878:65-70[Medline].

16. Ikewaki, K., Zech, L. A., Kindt, M., Brewer, H. B., Jr., Rader, D. J. 1995. Apolipoprotein A-II production rate is a major factor regulating the distribution of apolipoprotein A-I among HDL subclasses LpA-I and LpA-I:A-II in normolipidemic humans. Arterioscler. Thromb. Vasc. Biol. 15:306-312[Abstract/Free Full Text].

17. Bu, X., Warden, C. H., Xia, Y. R., De Meester, C., Puppione, D. L., Teruya, S., Lokensgard, B., Daneshmand, S., Brown, J., Gray, R. J., Rotter, J. I., Lusis, A. J. 1994. Linkage analysis of the genetic determinants of high density lipoprotein concentrations and composition: evidence for involvement of the apolipoprotein A-II and cholesteryl ester transfer protein loci. Hum. Genet. 93:639-650[Medline].

18. Paigen, B., Ishida, B. Y., Verstuyft, J., Winters, R. B., Albee, D. 1990. Atherosclerosis susceptibility differences among progenitors of recombinant inbred strains of mice. Arteriosclerosis. 10:316-323[Abstract/Free Full Text].

19. Barrans, A., Collet, X., Barbaras, R., Jaspard, R., Manent, J., Vieu, C., Chap, H., Perret, B. 1994. Hepatic lipase induces the formation of pre-ß₁ high density lipoprotein (HDL) from triacylglycerol-rich HDL₂. J. Biol. Chem. 269:11572-11577[Abstract/Free Full Text].

20. Castro, G., Nihoul, L. P., Dengremont, C., de Geitère, C., Delfly, B., Tailleux, A., Fievet, C., Duverger, N., Denèfle, P., Fruchart, J. C., Rubin, E. M. 1997. Cholesterol efflux, lecithin:cholesterol acyltransferase activity, and pre-ß particle formation by serum from human apolipoprotein A-I and apolipoprotein A-I/A-II transgenic mice consistent with the latter being less effective for reverse cholesterol transport. Biochemistry. 36:2243-2249[Medline].

21. Warden, C. H., Daluiski, A., Bu, X., Purcell-Huynh, D. A., De Meester, C., Shieh, B-H., Puppione, D. L., Gray, R. M., Reaven, G. M., Chen, Y-D., Rotter, J. I., Lusis, A. J. 1993. Evidence for linkage of the apolipoprotein A-II locus to plasma apolipoprotein A-II and free fatty acid levels in mice. Proc. Natl. Acad. Sci. USA. 90:10886-10890[Abstract/Free Full Text].

22. Weng, W., Breslow, J. L. 1996. Dramatically decreased high density lipoprotein cholesterol, increased remnant clearance, and insulin hypersensitivity in apoA-II knockout mice suggest a complex role for apolipoprotein A-II in atherosclerosis susceptibility. Proc. Natl. Acad. Sci. USA. 93:14788-14794[Abstract/Free Full Text].

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				L. W. Castellani, C. N. Nguyen, S. Charugundla, M. M. Weinstein, C. X. Doan, W. S. Blaner, N. Wongsiriroj, and A. J. Lusis Apolipoprotein AII Is a Regulator of Very Low Density Lipoprotein Metabolism and Insulin Resistance J. Biol. Chem., April 25, 2008; 283(17): 11633 - 11644. [Abstract] [Full Text] [PDF]

				R. S. Birjmohun, G. M. Dallinga-Thie, J. A. Kuivenhoven, E. S.G. Stroes, J. D. Otvos, N. J. Wareham, R. Luben, J. J.P. Kastelein, K.-T. Khaw, and S. M. Boekholdt Apolipoprotein A-II Is Inversely Associated With Risk of Future Coronary Artery Disease Circulation, October 30, 2007; 116(18): 2029 - 2035. [Abstract] [Full Text] [PDF]

				D. Corella, D. K. Arnett, M. Y. Tsai, E. K. Kabagambe, J. M. Peacock, J. E. Hixson, R. J. Straka, M. Province, C.-Q. Lai, L. D. Parnell, et al. The -256T>C Polymorphism in the Apolipoprotein A-II Gene Promoter Is Associated with Body Mass Index and Food Intake in the Genetics of Lipid Lowering Drugs and Diet Network Study Clin. Chem., June 1, 2007; 53(6): 1144 - 1152. [Abstract] [Full Text] [PDF]

				R. A. G. D. Silva, L. A. Schneeweis, S. C. Krishnan, X. Zhang, P. H. Axelsen, and W. S. Davidson The Structure of Apolipoprotein A-II in Discoidal High Density Lipoproteins J. Biol. Chem., March 30, 2007; 282(13): 9713 - 9721. [Abstract] [Full Text] [PDF]

				S. E. Nissen, S. J. Nicholls, K. Wolski, D. C. Howey, E. McErlean, M.-D. Wang, E. V. Gomez, and J. M. Russo Effects of a Potent and Selective PPAR-{alpha} Agonist in Patients With Atherogenic Dyslipidemia or Hypercholesterolemia: Two Randomized Controlled Trials JAMA, March 28, 2007; 297(12): 1362 - 1373. [Abstract] [Full Text] [PDF]

				N. Rotllan, V. Ribas, L. Calpe-Berdiel, J. M. Martin-Campos, F. Blanco-Vaca, and J. C. Escola-Gil Overexpression of Human Apolipoprotein A-II in Transgenic Mice Does Not Impair Macrophage-Specific Reverse Cholesterol Transport In Vivo Arterioscler. Thromb. Vasc. Biol., September 1, 2005; 25(9): e128 - e132. [Abstract] [Full Text] [PDF]

				L. W. Castellani, P. Gargalovic, M. Febbraio, S. Charugundla, M.-L. Jien, and A. J. Lusis Mechanisms mediating insulin resistance in transgenic mice overexpressing mouse apolipoprotein A-II J. Lipid Res., December 1, 2004; 45(12): 2377 - 2387. [Abstract] [Full Text] [PDF]

				V. Ribas, J. L. Sanchez-Quesada, R. Anton, M. Camacho, J. Julve, J. C. Escola-Gil, L. Vila, J. Ordonez-Llanos, and F. Blanco-Vaca Human Apolipoprotein A-II Enrichment Displaces Paraoxonase From HDL and Impairs Its Antioxidant Properties: A New Mechanism Linking HDL Protein Composition and Antiatherogenic Potential Circ. Res., October 15, 2004; 95(8): 789 - 797. [Abstract] [Full Text] [PDF]

				M. C. de Beer, L. W. Castellani, L. Cai, A. J. Stromberg, F. C. de Beer, and D. R. van der Westhuyzen ApoA-II modulates the association of HDL with class B scavenger receptors SR-BI and CD36 J. Lipid Res., April 1, 2004; 45(4): 706 - 715. [Abstract] [Full Text] [PDF]

				D. Sauvaget, V. Chauffeton, S. Dugue-Pujol, A.-D. Kalopissis, I. Guillet-Deniau, F. Foufelle, J. Chambaz, A. Leturque, P. Cardot, and A. Ribeiro In Vitro Transcriptional Induction of the Human Apolipoprotein A-II Gene by Glucose Diabetes, March 1, 2004; 53(3): 672 - 678. [Abstract] [Full Text] [PDF]

				H. Allayee, L. W. Castellani, R. M. Cantor, T. W.A. de Bruin, and A. J. Lusis Biochemical and Genetic Association of Plasma Apolipoprotein A-II Levels With Familial Combined Hyperlipidemia Circ. Res., June 13, 2003; 92(11): 1262 - 1267. [Abstract] [Full Text] [PDF]

				J. Julve, J. C. Escola-Gil, V. Ribas, F. Gonzalez-Sastre, J. Ordonez-Llanos, J. L. Sanchez-Quesada, and F. Blanco-Vaca Mechanisms of HDL deficiency in mice overexpressing human apoA-II J. Lipid Res., October 1, 2002; 43(10): 1734 - 1742. [Abstract] [Full Text] [PDF]

				E. Boisfer, D. Stengel, D. Pastier, P. M. Laplaud, N. Dousset, E. Ninio, and A.-D. Kalopissis Antioxidant properties of HDL in transgenic mice overexpressing human apolipoprotein A-II J. Lipid Res., May 1, 2002; 43(5): 732 - 741. [Abstract] [Full Text] [PDF]

				N. Fournier, A. Cogny, V. Atger, D. Pastier, D. Goudouneche, A. Nicoletti, N. Moatti, J. Chambaz, J.-L. Paul, and A.-D. Kalopissis Opposite Effects of Plasma From Human Apolipoprotein A-II Transgenic Mice on Cholesterol Efflux From J774 Macrophages and Fu5AH Hepatoma Cells Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 638 - 643. [Abstract] [Full Text] [PDF]

				L. W. Castellani and A. J. Lusis ApoA-II Versus ApoA-I: Two for One Is Not Always a Good Deal Arterioscler. Thromb. Vasc. Biol., December 1, 2001; 21(12): 1870 - 1872. [Full Text] [PDF]

				F. Blanco-Vaca, J. C. Escola-Gil, J. M. Martin-Campos, and J. Julve Role of apoA-II in lipid metabolism and atherosclerosis: advances in the study of an enigmatic protein J. Lipid Res., November 1, 2001; 42(11): 1727 - 1739. [Abstract] [Full Text] [PDF]

				C. C. Hedrick, L. W. Castellani, H. Wong, and A. J. Lusis In vivo interactions of apoA-II, apoA-I, and hepatic lipase contributing to HDL structure and antiatherogenic functions J. Lipid Res., April 1, 2001; 42(4): 563 - 570. [Abstract] [Full Text]

				J. C. Escolà-Gil, J. Julve, A. Marzal-Casacuberta, J. Ordóñez-Llanos, F. González-Sastre, and F. Blanco-Vaca ApoA-II expression in CETP transgenic mice increases VLDL production and impairs VLDL clearance J. Lipid Res., February 1, 2001; 42(2): 241 - 248. [Abstract] [Full Text]

				A. von Eckardstein, J.-R. Nofer, and G. Assmann High Density Lipoproteins and Arteriosclerosis : Role of Cholesterol Efflux and Reverse Cholesterol Transport Arterioscler. Thromb. Vasc. Biol., January 1, 2001; 21(1): 13 - 27. [Abstract] [Full Text] [PDF]

				A. Tailleux, M. Bouly, G. Luc, G. Castro, J.-M. Caillaud, N. Hennuyer, P. Poulain, J.-C. Fruchart, N. Duverger, and C. Fievet Decreased Susceptibility to Diet-Induced Atherosclerosis in Human Apolipoprotein A-II Transgenic Mice Arterioscler. Thromb. Vasc. Biol., November 1, 2000; 20(11): 2453 - 2458. [Abstract] [Full Text] [PDF]

				J. C. Escolà-Gil, J. Julve, A. Marzal-Casacuberta, J. Ordóñez-Llanos, F. González-Sastre, and F. Blanco-Vaca Expression of human apolipoprotein A-II in apolipoprotein E-deficient mice induces features of familial combined hyperlipidemia J. Lipid Res., August 1, 2000; 41(8): 1328 - 1338. [Abstract] [Full Text]

				J. C. Escola-Gil, O. Jorba, J. Julve-Gil, F. Gonzalez-Sastre, J. Ordonez-Llanos, and F. Blanco-Vaca Pitfalls of Direct HDL-Cholesterol Measurements in Mouse Models of Hyperlipidemia and Atherosclerosis Clin. Chem., September 1, 1999; 45(9): 1567 - 1569. [Full Text] [PDF]

				E. Boisfer, G. Lambert, V. Atger, N. Q. Tran, D. Pastier, C. Benetollo, J.-F. Trottier, I. Beaucamps, M. Antonucci, M. Laplaud, et al. Overexpression of Human Apolipoprotein A-II in Mice Induces Hypertriglyceridemia Due to Defective Very Low Density Lipoprotein Hydrolysis J. Biol. Chem., April 23, 1999; 274(17): 11564 - 11572. [Abstract] [Full Text] [PDF]

				N. Fournier, A. Cogny, V. Atger, D. Pastier, D. Goudouneche, A. Nicoletti, N. Moatti, J. Chambaz, J.-L. Paul, and A.-D. Kalopissis Opposite Effects of Plasma From Human Apolipoprotein A-II Transgenic Mice on Cholesterol Efflux From J774 Macrophages and Fu5AH Hepatoma Cells Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 638 - 643. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Escolà-Gil, J. C. Articles by Blanco-Vaca, F. Search for Related Content PubMed PubMed Citation Articles by Escolà-Gil, J. C. Articles by Blanco-Vaca, F. Social Bookmarking                      What's this?

<