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Neurotensin accelerates atherosclerosis and increases circulating levels of short-chain and saturated triglycerides.
- Source :
-
Atherosclerosis [Atherosclerosis] 2024 May; Vol. 392, pp. 117479. Date of Electronic Publication: 2024 Feb 15. - Publication Year :
- 2024
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Abstract
- Background and Aims: Obesity and type 2 diabetes are significant risk factors for atherosclerotic cardiovascular disease (CVD) worldwide, but the underlying pathophysiological links are poorly understood. Neurotensin (NT), a 13-amino-acid hormone peptide, facilitates intestinal fat absorption and contributes to obesity in mice fed a high-fat diet. Elevated levels of pro-NT (a stable NT precursor produced in equimolar amounts relative to NT) are associated with obesity, type 2 diabetes, and CVD in humans. Whether NT is a causative factor in CVD is unknown.<br />Methods: Nt <superscript>+/+</superscript> and Nt <superscript>-/-</superscript> mice were either injected with adeno-associated virus encoding PCSK9 mutants or crossed with Ldlr <superscript>-/-</superscript> mice and fed a Western diet. Atherosclerotic plaques were analyzed by en face analysis, Oil Red O and CD68 staining. In humans, we evaluated the association between baseline pro-NT and growth of carotid bulb thickness after 16.4 years. Lipidomic profiles were analyzed.<br />Results: Atherosclerotic plaque formation is attenuated in Nt-deficient mice through mechanisms that are independent of reductions in circulating cholesterol and triglycerides but associated with remodeling of the plasma triglyceride pool. An increasing plasma concentration of pro-NT predicts atherosclerotic events in coronary and cerebral arteries independent of all major traditional risk factors, indicating a strong link between NT and atherosclerosis. This plasma lipid profile analysis confirms the association of pro-NT with remodeling of the plasma triglyceride pool in atherosclerotic events.<br />Conclusions: Our findings are the first to directly link NT to increased atherosclerosis and indicate the potential role for NT in preventive and therapeutic strategies for CVD.<br /> (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Female
Humans
Male
Mice
Disease Models, Animal
Fatty Acids metabolism
Fatty Acids blood
Mice, Inbred C57BL
Mice, Knockout
Protein Precursors
Receptors, LDL genetics
Receptors, LDL deficiency
Risk Factors
Atherosclerosis blood
Neurotensin blood
Neurotensin genetics
Neurotensin metabolism
Plaque, Atherosclerotic
Triglycerides blood
Triglycerides metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-1484
- Volume :
- 392
- Database :
- MEDLINE
- Journal :
- Atherosclerosis
- Publication Type :
- Academic Journal
- Accession number :
- 38423808
- Full Text :
- https://doi.org/10.1016/j.atherosclerosis.2024.117479