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Distinct lipidomic profiles in models of physiological and pathological cardiac remodeling, and potential therapeutic strategies.
- Source :
-
Biochimica et biophysica acta. Molecular and cell biology of lipids [Biochim Biophys Acta Mol Cell Biol Lipids] 2018 Mar; Vol. 1863 (3), pp. 219-234. Date of Electronic Publication: 2017 Dec 06. - Publication Year :
- 2018
-
Abstract
- Cardiac myocyte membranes contain lipids which remodel dramatically in response to heart growth and remodeling. Lipid species have both structural and functional roles. Physiological and pathological cardiac remodeling have very distinct phenotypes, and the identification of molecular differences represent avenues for therapeutic interventions. Whether the abundance of specific lipid classes is different in physiological and pathological models was largely unknown. The aim of this study was to determine whether distinct lipids are regulated in settings of physiological and pathological remodeling, and if so, whether modulation of differentially regulated lipids could modulate heart size and function. Lipidomic profiling was performed on cardiac-specific transgenic mice with 1) physiological cardiac hypertrophy due to increased Insulin-like Growth Factor 1 (IGF1) receptor or Phosphoinositide 3-Kinase (PI3K) signaling, 2) small hearts due to depressed PI3K signaling (dnPI3K), and 3) failing hearts due to dilated cardiomyopathy (DCM). In hearts of dnPI3K and DCM mice, several phospholipids (plasmalogens) were decreased and sphingolipids increased compared to mice with physiological hypertrophy. To assess whether restoration of plasmalogens could restore heart size or cardiac function, dnPI3K and DCM mice were administered batyl alcohol (BA; precursor to plasmalogen biosynthesis) in the diet for 16weeks. BA supplementation increased a major plasmalogen species (p18:0) in the heart but had no effect on heart size or function. This may be due to the concurrent reduction in other plasmalogen species (p16:0 and p18:1) with BA. Here we show that lipid species are differentially regulated in settings of physiological and pathological remodeling. Restoration of lipid species in the failing heart warrants further examination.<br /> (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Cardiomegaly drug therapy
Cardiomegaly genetics
Cardiomegaly pathology
Mice
Mice, Transgenic
Myocardium pathology
Plasmalogens genetics
Ventricular Remodeling genetics
Cardiomegaly metabolism
Glyceryl Ethers pharmacology
Lipid Metabolism drug effects
Myocardium metabolism
Plasmalogens metabolism
Ventricular Remodeling drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1388-1981
- Volume :
- 1863
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta. Molecular and cell biology of lipids
- Publication Type :
- Academic Journal
- Accession number :
- 29217479
- Full Text :
- https://doi.org/10.1016/j.bbalip.2017.12.003