Hypertriglyceridemia: molecular and genetic landscapes
Open accessAbstract
Lipid disorders represent one of the most worrisome cardiovascular risk factors. The focus on the impact of lipids on cardiac and vascular health usually concerns low-density lipoprotein cholesterol, while the role of triglycerides (TGs) is given poor attention. The literature provides data on the impact of higher plasma concentrations in TGs on the cardiovascular system and, therefore, on the outcomes and comorbidities of patients. The risk for coronary heart diseases varies from 57 to 76% in patients with hypertriglyceridemia. Specifically, the higher the plasma concentrations in TGs, the higher the incidence and prevalence of death, myocardial infarction, and stroke. Nevertheless, the metabolism of TGs and the exact physiopathologic mechanisms which try to explain the relationship between TGs and cardiovascular outcomes are not completely understood. The aims of this narrative review were as follows: to provide a comprehensive evaluation of the metabolism of triglycerides and a possible suggestion for understanding the targets for counteracting hypertriglyceridemia; to describe the inner physiopathological background for the relationship between vascular and cardiac damages derived from higher plasma concentrations in TGs; and to outline the need for promoting further insights in therapies for reducing TGs plasma levels.
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Regulatory proteins such as APOC3 and ANGPTL3 play central roles in modulating lipoprotein lipase activity, hepatic lipoprotein production, and remnant metabolism.
“Regulatory proteins such as APOC3 and ANGPTL3 play central roles in modulating lipoprotein lipase activity, hepatic lipoprotein production, and remnant metabolism, providing a strong biological rationale for target-specific therapeutic strategies (Scicchitano et al., 2024).”
From Efficacy and safety of small interfering RNA (siRNA) therapies for hypertriglyceridemia and mixed dyslipidemia: an updated systematic review and meta-analysis (2026) · cites this paper as Scicchitano et al., 2024
Section 3 identifies apoC-III as an inhibitor of lipoprotein lipase (LPL), and §4.1 says the ANGPTL3 pathway inhibits LPL; §3 also links LPL activity to chylomicron-remnant formation. But the paper does not attribute hepatic lipoprotein production or hepatic remnant uptake to APOC3 and ANGPTL3 as the claim suggests; §3 instead describes other factors in those processes. (LLM, conf=0.86)
Experimental — accuracy not yet measuredHypertriglyceridemia is a biologically heterogeneous condition arising from complex interactions between genetic predisposition and metabolic regulation.
“Hypertriglyceridemia is a biologically heterogeneous condition arising from complex interactions between genetic predisposition and metabolic regulation.”
From Efficacy and safety of small interfering RNA (siRNA) therapies for hypertriglyceridemia and mixed dyslipidemia: an updated systematic review and meta-analysis (2026) · cites this paper as Scicchitano et al., 2024
Both rare monogenic defects affecting key components of the lipoprotein lipase pathway and more common polygenic susceptibility contribute to impaired triglyceride-rich lipoprotein clearance and variable clinical phenotypes.
“As summarized by Scicchitano et al., both rare monogenic defects affecting key components of the lipoprotein lipase pathway and more common polygenic susceptibility contribute to impaired triglyceride-rich lipoprotein clearance and variable clinical phenotypes.”
From Efficacy and safety of small interfering RNA (siRNA) therapies for hypertriglyceridemia and mixed dyslipidemia: an updated systematic review and meta-analysis (2026) · cites this paper as Scicchitano et al., 2024
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Bermúdez, B., López, S., Varela, L. M., Ortega‐Gómez, A., Pacheco, Y. M., Moreda, W., Moreno‐Luna, R., Abia, R., & Muriana, F. J. G. (2011) · Journal of Nutrition · doi:10.3945/jn.111.149963 · Cited by 26 · see citing works
Biochemical characterization of human acyl coenzyme A: 2-monoacylglycerol acyltransferase-3 (MGAT3)
Brandt, C., McFie, P. J., & Stone, S. J. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.05.071 · Cited by 23 · see citing works
Bednarski, T. K., Duda, M. K., & Dobrzyń, P. (2022) · Cells · doi:10.3390/cells11193032 · Cited by 21 · see citing works
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Takaeko, Y., Maruhashi, T., Kajikawa, M., Kishimoto, S., Yamaji, T., Harada, T., Hashimoto, Y., Han, Y., Kihara, Y., Chayama, K., et al. (2021) · Journal of clinical lipidology · doi:10.1016/j.jacl.2021.04.004 · Cited by 19 · see citing works
Hypertriglyceridemia: Pathophysiology, Role of Genetics, Consequences, and Treatment
Chait, A., & Subramanian, S. (2000) · Europe PMC (PubMed Central) · Cited by 18 · see citing works
Banh, T., Nelson, D. W., Gao, Y., Huang, T.-N., Yen, M., & Yen, C. E. (2014) · Journal of Lipid Research · doi:10.1194/jlr.m055228 · Cited by 16 · see citing works
Pontremoli, R., Desideri, G., Arca, M., Temporelli, P., Perrone, V., Dovizio, M., Borghi, C., & Esposti, L. (2023) · European journal of internal medicine · doi:10.1016/j.ejim.2023.02.019 · Cited by 14 · see citing works
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Non-alcoholic fatty liver disease in patients with chylomicronemia syndromes
Villers-Lacasse, A. D., Paquette, M., Baass, A. W., & Bernard, S. (2023) · Journal of clinical lipidology · doi:10.1016/j.jacl.2023.05.096 · Cited by 9 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [49]Available online: https://www.ncbi.nlm.nih.gov/gene/27329 (accessed on 28 January 2023)
- [50]Available online: https://www.ncbi.nlm.nih.gov/gene/51129 (accessed on 28 January 2023)
Cited by
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ANGPTL3 and residual atherosclerotic risk: from lipid metabolism to therapeutic targeting
Weng, S., Ding, C., Lin, J., & Chai, D. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1706091 · Cited by 5 · see citing works
Gao, Y., Bai, Y., Mu, X., & Pang, X. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1736821 · Cited by 4 · see citing works
“As summarized by Scicchitano et al., both rare monogenic defects affecting key components of the lipoprotein lipase pathway and more common polygenic susceptibility contribute to impaired triglyceride-rich lipoprotein clearance and variable clinical phenotypes.”
Havelda, L., Szalai, E. Á., Obeidat, M., Dobszai, D., Veres, D. S., Kói, T., Sipter, E., Váncsa, S., Hegyi, P. J., Bucur, M., et al. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1710007 · Cited by 3 · see citing works
Shahparvari, M. R., & Nasrollahzadeh, J. (2024) · Journal of Human Nutrition and Dietetics · doi:10.1111/jhn.13369 · Cited by 3 · see citing works
Lai, Z., Liu, Z., Wang, X., Jiang, X., Yang, Y., Fan, X., Shi, Y., & Li, X. (2025) · Metabolism and Target Organ Damage · doi:10.20517/mtod.2025.20 · Cited by 3 · see citing works
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Self-citationTsai, H.-J., Yu, P.-S., Hung, W., Wu, P., Hung, W., Sl, H., Kuo, M., & Tsai, Y. (2026) · Postgraduate Medicine · doi:10.1080/00325481.2026.2641270 · Cited by 1 · see citing works
Gao, Z., Gao, Y., Fang, C., Chen, Z., Zhang, D., Hao, W., Jia, H., Hu, S., & Yu, B. (2026) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2025.1734117
Huang, Y., Gan, X., Liang, H., Tang, S., Chen, J., & Shi, Y. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1698418
Pavlova, O. N., Сергеевна, К. Е., & Shirolapov, I. V. (2025) · Экспериментальная и клиническая гастроэнтерология · doi:10.31146/1682-8658-ecg-235-3-270-277
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Hypertriglyceridemia: Causes, Consequences, Diagnosis, and Management
Qi, S., Chen, W., Chen, K., Yang, S., Wang, S., Ni, T., Xu, D., Mao, E., Chen, E., & Chen, Y. (2026) · MedComm · doi:10.1002/mco2.70956
- Authors
- Scicchitano, P., Amati, F., Ciccone, M. M., D’Ascenzi, F., Imbalzano, E., Liga, R., Paolillo, S., Pastore, M. C., Rinaldi, A., Mattioli, A. V., & Cameli, M.
- Affiliations
- Cardiology Department, Hospital “F Perinei” ASL BA, 70022 Altamura, Italy
- University of Bari Aldo Moro (IT)
- University of Siena (IT)
- University of Messina (IT)
- University of Pisa (IT)
- University of Naples Federico II (IT)
- IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
- University of Bologna (IT)
- Corresponding author
- Scicchitano, Pietro
- ORCID
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2024-06-08
- Volume
- 25
- Issue
- 12
- Pages
- 6364
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC11203941
- OpenAlex
- W4399511576
- Cited by
- 13
- References
- 92
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 1
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by)
- Use Siena air (University of Siena) (submittedVersion, cc-by)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- hypertriglyceridemia, triglycerides, triglyceride metabolism, cardiovascular risk, coronary artery disease, myocardial infarction, stroke, lipid metabolism disorders, genetic susceptibility, molecular mechanisms
- MeSH terms
- Animals, Cardiovascular Diseases, Humans, Risk Factors, Triglycerides, Hypertriglyceridemia, Lipid Metabolism
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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