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Angiopoietin-Like 3
- Source :
- JACC: Basic to Translational Science, Vol 4, Iss 6, Pp 755-762 (2019), JACC: Basic to Translational Science
- Publication Year :
- 2019
- Publisher :
- Elsevier, 2019.
-
Abstract
- Highlights • Individuals with ANGPTL3 loss-of-function mutations have reduced cholesterol levels, triglyceride levels, and risk of coronary heart disease, making ANGPTL3 a potential therapeutic target. • An antisense oligonucleotide inhibitor of ANGPTL3 and a monoclonal antibody against ANGPTL3 have been advanced into clinical trials, with encouraging results to date. • A distinct approach to targeting ANGPTL3 would be therapeutic gene editing in patients to induce permanent loss of function mutations mimicking those in individuals with naturally occurring cardioprotective mutations.<br />Summary Hyperlipidemia is a major causal risk factor for atherosclerosis and coronary heart disease (CHD). Angiopoietin-like 3 (ANGPTL3) has emerged as a promising molecular target to reduce CHD risk due to its regulation of all 3 major lipid traits: low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. Here, the authors review the discovery of ANGPTL3, the role of ANGPTL3 in lipoprotein metabolism, and the genetic association between naturally occurring ANGPTL3 loss-of-function mutations and CHD. In light of the favorable consequences of ANGPTL3 deficiency, various therapeutic strategies to target ANGPTL3 are currently in development, including a monoclonal antibody, an antisense oligonucleotide, and gene editing.<br />Central Illustration
- Subjects :
- 0301 basic medicine
lcsh:Diseases of the circulatory (Cardiovascular) system
medicine.drug_class
ANGPTL3, angiopoietin-like 3
ASO, antisense oligonucleotide
030204 cardiovascular system & hematology
Monoclonal antibody
Bioinformatics
CHD, coronary heart disease
STATE-OF-THE-ART REVIEW
Coronary artery disease
Angiopoietin
lipids
HDL-C, high-density lipoprotein cholesterol
03 medical and health sciences
0302 clinical medicine
Genome editing
ANGPTL3
Hyperlipidemia
medicine
genetics
cardiovascular diseases
Risk factor
hoFH, homozygous familial hypercholesterolemia
Genetic association
business.industry
medicine.disease
030104 developmental biology
lcsh:RC666-701
LDL-C, low-density lipoprotein cholesterol
lipids (amino acids, peptides, and proteins)
Cardiology and Cardiovascular Medicine
business
PCSK9, proprotein convertase subtilisin/kexin type 9
coronary artery disease
Subjects
Details
- Language :
- English
- Volume :
- 4
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- JACC: Basic to Translational Science
- Accession number :
- edsair.doi.dedup.....aca55ef485ae3a925933098583333f67