Apolipoprotein A-V gene therapy for disease prevention/treatment: a critical analysis
Open accessAbstract
Apolipoprotein (apo) A-V is a novel member of the class of exchangeable apo's involved in triacylglycerol (TG) homeostasis. Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilitate lipoprotein lipase-mediated TG hydrolysis, another portion is recovered intracellularly, in association with cytosolic lipid droplets. Loss of apoA-V function is positively correlated with elevated plasma TG and increased risk of cardiovascular disease. Single nucleotide polymorphisms (SNP) in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid substitutions. Likewise, rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial infarction. Genetically engineered mouse models and human population studies suggest that, in certain instances, supplementation with wild type (WT) apoA-V may have therapeutic benefit. It is hypothesized that individuals that manifest elevated plasma TG owing to deleterious APOA5 SNPs or rare mutations would respond to WT apoA-V supplementation with improved plasma TG clearance. On the other hand, subjects with hypertriglyceridemia of independent origin (unrelated to apoA-V function) may not respond to apoA-V augmentation in this manner. Improvement in the ability to identify individuals predicted to benefit, advances in gene transfer technology and the strong connection between HTG and heart disease, point to apoA-V supplementation as a viable disease prevention / therapeutic strategy. Candidates would include individuals that manifest chronic TG elevation, have low plasma apoA-V due to an APOA5 mutation/polymorphism and not have deleterious mutations/polymorphisms in other genes known to influence plasma TG levels.
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Apo A-V promotes LPL activity through partially defined mechanisms and is a strong genetically validated target for ASCVD.
“In contrast, apo A-V, which promotes LPL activity through partially defined mechanisms, is a strong genetically validated target for ASCVD.95,96”
From Clinical review on triglycerides (2020) · cites this paper as [95]
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Cites
Nordestgaard, B. G., Benn, M., Schnohr, P., & Tybjærg-Hansen, A. (2007) · JAMA · doi:10.1001/jama.298.3.299 · Cited by 2,058 · see citing works
Triglycerides and Cardiovascular Disease: A Scientific Statement From the American Heart Association
Miller, M., Stone, N. J., Ballantyne, C., Bittner, V., Criqui, M. H., Ginsberg, H. N., Goldberg, A. C., Howard, W. J., Jacobson, M. S., Kris-Etherton, P. M., et al. (2011) · Circulation · doi:10.1161/cir.0b013e3182160726 · Cited by 1,871 · see citing works
Gene therapy restores vision in a canine model of childhood blindness
Acland, G. M., Aguirre, G. D., Ray, J., Zhang, Q., Aleman, T. S., Cideciyan, A. V., Pearce-Kelling, S. E., Anand, V., Zeng, Y., Maguire, A. M., et al. (2001) · Nature Genetics · doi:10.1038/ng0501-92 · Cited by 1,202 · see citing works
Relation of triglyceride metabolism and coronary artery disease. Studies in the postprandial state
Patsch, J. R., Miesenböck, G., Hopferwieser, T., Mühlberger, V, Knapp, E., Dunn, J. K., Gotto, A. M., & Patsch, W. (1992) · Arteriosclerosis and Thrombosis: A Journal of Vascular Biology · doi:10.1161/01.atv.12.11.1336 · Cited by 1,122 · see citing works
An Apolipoprotein Influencing Triglycerides in Humans and Mice Revealed by Comparative Sequencing
Pennacchio, L. A., Olivier, M., Hubacek, J. A., Cohen, J. C., Cox, D. R., Fruchart, J.-C., Krauss, R. M., & Rubin, E. M. (2001) · Science · doi:10.1126/science.1064852 · Cited by 921 · see citing works
Xiao, X., Li, J., & Samulski, R. J. (1996) · Journal of Virology · doi:10.1128/jvi.70.11.8098-8108.1996 · Cited by 913 · see citing works
Assmann, G., & Schulte, H. (1992) · The American Journal of Cardiology · doi:10.1016/0002-9149(92)90550-i · Cited by 872 · see citing works
Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction
Do, R., Stitziel, N. O., Won, H.-H., Jørgensen, A. B., Duga, S., Angelica Merlini, P., Kiezun, A., Farrall, M., Goel, A., Zuk, O., et al. (2015) · Nature · doi:10.1038/nature13917 · Cited by 650 · see citing works
Pedersen, T. R., OLSSON, A. G., Færgeman, O., KJEKSHUS, J. K., Wedel, H., Berg, K., Wilhelmsen, L., Haghfelt, T. H., Þorgeirsson, G., Pyörälà, K., et al. (1998) · Circulation · doi:10.1161/01.cir.97.15.1453 · Cited by 618 · see citing works
Herzog, R. W., Yang, E. Y., Couto, L. B., Hagstrom, J. N., Elwell, D., Fields, P. A., Burton, M., Bellinger, D. A., Read, M. S., Brinkhous, K. M., et al. (1999) · Nature Medicine · doi:10.1038/4743 · Cited by 554 · see citing works
Hypertriglyceridemia as a Result of Human apo <i>CII</i> Gene Expression in Transgenic Mice
Ito, Y., Azrolan, N., O'Connell, A., Walsh, A., & Breslow, J. L. (1990) · Science · doi:10.1126/science.2167514 · Cited by 539 · see citing works
Beigneux, A. P., Davies, B. S. J., Gin, P., Weinstein, M. M., Farber, E., Qiao, X., Peale, F. V., Jr., Bunting, S., Walzem, R. L., Wong, J. S., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.02.002 · Cited by 470 · see citing works
McCown, T. J., Xiao, X., Li, J., Breese, G. R., & Samulski, R. J. (1996) · Brain Research · doi:10.1016/0006-8993(95)01488-8 · Cited by 450 · see citing works
Aalto‐Setälä, K., Fisher, E. A. A., Chen, X., Chajek‐Shaul, T., Hayek, T., Zechner, R., Walsh, A., Ramakrishnan, R., Ginsberg, H. N., & Breslow, J. L. (1992) · Journal of Clinical Investigation · doi:10.1172/jci116066 · Cited by 450 · see citing works
Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia
Johansen, C. T., Wang, J., Lanktree, M. B., Cao, H., McIntyre, A. D., Ban, M. R., Martins, R. A., Kennedy, B. A., Hassell, R. G., Visser, M. E., et al. (2010) · Nature Genetics · doi:10.1038/ng.628 · Cited by 437 · see citing works
Ballantyne, C. M., Olsson, A. G., Cook, T. J., Mercuri, M. F., Pedersen, T. R., & Kjekshus, J. (2001) · Circulation · doi:10.1161/hc5001.100624 · Cited by 416 · see citing works
Snyder, R. O., Miao, C., Meuse, L., Tubb, J., Donahue, B. A., Lin, H.-F., Stafford, D. W., Patel, S., Thompson, A. R., Nichols, T., et al. (1999) · Nature Medicine · doi:10.1038/4751 · Cited by 409 · see citing works
Gaudet, D., Méthot, J., Déry, S., Brisson, D., Essiembre, C., Tremblay, G., Tremblay, K., de Wal, J., Twisk, J., van den Bulk, N., et al. (2013) · Gene Therapy · doi:10.1038/gt.2012.43 · Cited by 404 · see citing works
Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels
Pennacchio, L. A. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.24.3031 · Cited by 381 · see citing works
Thomas, C. E., Storm, T. A., Huang, Z., & Kay, M. A. (2004) · Journal of Virology · doi:10.1128/jvi.78.6.3110-3122.2004 · Cited by 358 · see citing works
Zilversmit, D. B. (1973) · Circulation Research · doi:10.1161/01.res.33.6.633 · Cited by 338 · see citing works
Serum Triglycerides and Risk of Coronary Heart Disease among Japanese Men and Women
Iso, H., Naito, Y., Sato, S., Kitamura, A., Okamura, T., Sankai, T., Shimamoto, T., Iida, M., & Komachi, Y. (2001) · American Journal of Epidemiology · doi:10.1093/aje/153.5.490 · Cited by 325 · see citing works
Regulated Delivery of Therapeutic Proteins After in Vivo Somatic Cell Gene Transfer
Ye, X., Rivera, V. M., Zoltick, P. W., Cerasoli, F., Schnell, M. A., Gao, G., Hughes, J. V., Gilman, M. Z., & Wilson, J. M. (1999) · Science · doi:10.1126/science.283.5398.88 · Cited by 308 · see citing works
Monahan, P. E., Samulski, R. J., Tazelaar, J., Xiao, X., Nichols, T. C., Bellinger, D., Read, M., & Walsh, C. (1998) · Gene Therapy · doi:10.1038/sj.gt.3300548 · Cited by 202 · see citing works
Marçais, C. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24471 · Cited by 169 · see citing works
Prevalence of Severe (500 to 2,000 mg/dl) Hypertriglyceridemia in United States Adults
Christian, J. B., Bourgeois, N., Snipes, R., & Lowe, K. A. (2011) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2010.11.008 · Cited by 155 · see citing works
Song, S., Embury, J. E., Laipis, P., Berns, K., Crawford, J., & Flotte, T. R. (2001) · Gene Therapy · doi:10.1038/sj.gt.3301422 · Cited by 152 · see citing works
Triglycerides as vascular risk factors: new epidemiologic insights.
Kannel, W. B., & Vasan, R. S. (2009) · Current Opinion in Cardiology · doi:10.1097/hco.0b013e32832c1284 · Cited by 149 · see citing works
Elevated Serum Triglyceride Levels and Long-Term Mortality in Patients With Coronary Heart Disease
Haim, M., Benderly, M., Brunner, D., Behar, S., Graff, E., Reicher-Reiss, H., & Goldbourt, U. (1999) · Circulation · doi:10.1161/01.cir.100.5.475 · Cited by 138 · see citing works
Apolipoprotein A-V-heparin Interactions
Lõokene, A., Beckstead, J. A., Nilsson, S., Olivecrona, G., & Ryan, R. O. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501589200 · Cited by 130 · see citing works
Determination of the Functionality of Common APOA5 Polymorphisms
Talmud, P. J., Palmen, J., Putt, W., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502144200 · Cited by 117 · see citing works
Aalto‐Setälä, K., Weinstock, P. H., Bisgaier, C. L., Wu, L., Smith, J. D., & Breslow, J. L. (1996) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)39123-9 · Cited by 114 · see citing works
Eiselein, L., Wilson, D. W., Lamé, M. W., & Rutledge, J. C. (2007) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00686.2006 · Cited by 105 · see citing works
APOA5 and triglyceride metabolism, lesson from human APOA5 deficiency
Calandra, S., Oliva, C. P., Tarugi, P., & Bertolini, S. (2006) · Current Opinion in Lipidology · doi:10.1097/01.mol.0000217892.00618.54 · Cited by 103 · see citing works
Apolipoprotein A-V Interaction with Members of the Low Density Lipoprotein Receptor Gene Family
Nilsson, S. K., Lõokene, A., Beckstead, J. A., Gliemann, J., Ryan, R. O., & Olivecrona, G. (2007) · Biochemistry · doi:10.1021/bi7000533 · Cited by 102 · see citing works
Mamo, J. C. L., Proctor, S. D., & Smith, D. (1998) · Atherosclerosis · doi:10.1016/s0021-9150(98)00220-2 · Cited by 98 · see citing works
Adeno-associated virus-mediated delivery of IL-4 prevents collagen-induced arthritis
Cottard, V., Mulleman, D., Bouillé, P., Mezzina, M., Boissier, M., & Bessis, N. (2000) · Gene Therapy · doi:10.1038/sj.gt.3301324 · Cited by 93 · see citing works
Give me A5 for lipoprotein hydrolysis!
Merkel, M. (2005) · Journal of Clinical Investigation · doi:10.1172/jci26712 · Cited by 92 · see citing works
Apolipoproteins E and AV mediate lipoprotein clearance by hepatic proteoglycans
Gonzales, J. C., Gordts, P. L. S. M., Foley, E. M., & Esko, J. D. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67398 · Cited by 79 · see citing works
Henneman, P., Schaap, F. G., Havekes, L. M., Rensen, P. C. N., Frants, R. R., van Tol, A., Hattori, H., Smelt, A. H. M., & van Dijk, K. W. (2006) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2006.05.030 · Cited by 76 · see citing works
MAHLEY, R. W., INNERARITY, T. L., RALL, S. C., & WEISGRABER, K. H. (1985) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1985.tb11860.x · Cited by 75 · see citing works
Pullinger, C. R., Aouizerat, B. E., Movsesyan, I., Durlach, V., Sijbrands, E. J. G., Nakajima, K., Poon, A., Dallinga‐Thie, G. M., Hattori, H., Green, L., et al. (2008) · Journal of Lipid Research · doi:10.1194/jlr.p800011-jlr200 · Cited by 68 · see citing works
Li, J., Wang, D., Qian, S., Chen, Z., Zhu, T., & Xiao, X. (2003) · Gene Therapy · doi:10.1038/sj.gt.3302078 · Cited by 63 · see citing works
Effects of apoA-V on HDL and VLDL metabolism in APOC3 transgenic mice
Qu, S., Perdomo, G., Su, D., D’Souza, F. M., Shachter, N. S., & Dong, H. H. (2007) · Journal of Lipid Research · doi:10.1194/jlr.m600498-jlr200 · Cited by 59 · see citing works
Alipogene tiparvovec: gene therapy for lipoprotein lipase deficiency
Wierzbicki, A. S., & Viljoen, A. (2012) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2013.738663 · Cited by 48 · see citing works
Shu, X., Nelbach, L., Weinstein, M. M., Burgess, B. L., Beckstead, J. A., Young, S. G., Ryan, R. O., & Forte, T. M. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.210815 · Cited by 47 · see citing works
A novel sequence variant in APOA5 gene found in patients with severe hypertriglyceridemia
Oliva, C. P., Pisciotta, L., Guardamagna, O., et al. (2006) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2006.04.010 · Cited by 43 · see citing works
Atheroprotective Effect of Human Apolipoprotein A5 in a Mouse Model of Mixed Dyslipidemia
Mansouri, R. M., Baugé, E., Gervois, P. P., Fruchart‐Najib, J., Fiévet, C., Staels, B., & Fruchart, J. (2008) · Circulation Research · doi:10.1161/circresaha.108.179861 · Cited by 40 · see citing works
Influence of apolipoprotein A-V on the metabolic fate of triacylglycerol
Sharma, V., Forte, T. M., & Ryan, R. O. (2012) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32835c8c1a · Cited by 39 · see citing works
Albers, K., Schlein, C., Wenner, K., Lohse, P., Bartelt, A., Heeren, J., Santer, R., & Merkel, M. (2014) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2013.12.009 · Cited by 30 · see citing works
Recombinant adeno-associated virus vectors for cystic fibrosis gene therapy.
Flotte, T. R. (2001) · PubMed · Cited by 24 · see citing works
Grosskopf, I., Shaish, A., Afek, A. B., Shemesh, S., Harats, D., & Kamari, Y. (2012) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2012.04.011 · Cited by 21 · see citing works
Sharma, V., Witkowski, A., Witkowska, H. E., Dykstra, A. B., Simonsen, J. B., Nelbach, L., Beckstead, J. A., Pullinger, C. R., Kane, J. P., Malloy, M. J., et al. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.304027 · Cited by 21 · see citing works
Gene Transfer of Apolipoprotein A-V Improves the Hypertriglyceridemic Phenotype of apoa5 (−/−) mice
Sharma, V., Beckstead, J. A., Simonsen, J. B., et al. (2013) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.112.301078 · Cited by 15 · see citing works
Hypercholesterolemia and dyslipidemia
Superko, H. R. (2000) · Current Treatment Options in Cardiovascular Medicine · doi:10.1007/s11936-000-0010-5 · Cited by 10 · see citing works
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- [33]Sharma V, Witkowski A, Witskowaski E Hyper-triglyceridemia associated with the c.553G>T APOA-V SNP results from aberrant hetero-disulfide bond formation[J] Arterioscler Thromb Vasc Biol 2014 34 10 2254 2260 25127531 PMC4178935
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- Authors
- Trudy, M., Vineeta, S., & Robert, O.
- Corresponding author
- Robert, O.
- Venue
- The Journal of Biomedical Research
- Publisher
- Journal of Biomedical Research
- Published
- 2016
- Volume
- 30
- Issue
- 2
- Pages
- 88
- ISSN
- 1674-8301 (ISSN-L)
- PMC
- PMC4820885
- OpenAlex
- W2209861769
- Cited by
- 18
- References
- 55
- Citations by year
- 2023: 1 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 4
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Journal of Biomedical Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R37HL064159)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Keywords
- apolipoprotein A-V, hypertriglyceridemia, lipoprotein lipase, cardiovascular risk, gene transfer
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