2. Academic Validation
  3. Angiopoietin-Like Protein 3 (ANGPTL3) Modulates Lipoprotein Metabolism and Dyslipidemia

Angiopoietin-Like Protein 3 (ANGPTL3) Modulates Lipoprotein Metabolism and Dyslipidemia

  • Int J Mol Sci. 2021 Jul 7;22(14):7310. doi: 10.3390/ijms22147310.
Pei-Yi Chen 1 2,  Wan-Yun Gao 3,  Je-Wen Liou 4,  Ching-Yen Lin 2,  Ming-Jiuan Wu 5,  Jui-Hung Yen 2 3
Affiliations

Affiliations

  • 1 Center of Medical Genetics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan.
  • 2 Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 970, Taiwan.
  • 3 Institute of Medical Sciences, Tzu Chi University, Hualien 970, Taiwan.
  • 4 Department of Biochemistry, School of Medicine, Tzu Chi University, Hualien 970, Taiwan.
  • 5 Department of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan.
PMID: 34298929 DOI: 10.3390/ijms22147310
Abstract

Dyslipidemia is characterized by increasing plasma levels of low-density lipoprotein-cholesterol (LDL-C), triglycerides (TGs) and TG-rich lipoproteins (TGRLs) and is a major risk factor for the development of atherosclerotic cardiovascular disorders (ASCVDs). It is important to understand the metabolic mechanisms underlying dyslipidemia to develop effective strategies against ASCVDs. Angiopoietin-like 3 (ANGPTL3), a member of the angiopoietin-like protein family exclusively synthesized in the liver, has been demonstrated to be a critical regulator of lipoprotein metabolism to inhibit lipoprotein Lipase (LPL) activity. Genetic, biochemical, and clinical studies in Animals and humans have shown that loss of function, inactivation, or downregulated expression of ANGPTL3 is associated with an obvious reduction in plasma levels of TGs, LDL-C, and high-density lipoprotein-cholesterol (HDL-C), atherosclerotic lesions, and the risk of cardiovascular events. Therefore, ANGPTL3 is considered an alternative target for lipid-lowering therapy. Emerging studies have focused on ANGPTL3 inhibition via Antisense Oligonucleotides (ASOs) and monoclonal antibody-based therapies, which have been carried out in mouse or monkey models and in human clinical studies for the management of dyslipidemia and ASCVDs. This review will summarize the current literature on the important role of ANGPTL3 in controlling lipoprotein metabolism and dyslipidemia, with an emphasis on anti-ANGPTL3 therapies as a potential strategy for the treatment of dyslipidemia and ASCVDs.

Keywords

ANGPTL3; ASCVDs; TG-rich lipoproteins; dyslipidemia; lipoprotein lipase.

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