Left ventricular hypertrophy and metabolic resetting in the Notch3-deficient adult mouse heart
Abstract The heart depends on a functional vasculature for oxygenation and transport of nutrients, and it is of interest to learn how primary impairment of the vasculature can indirectly affect cardiac function and heart morphology. Notch3 -deficiency causes vascular smooth muscle cell (VSMC) loss i...
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Published in | Scientific reports Vol. 13; no. 1; pp. 15022 - 14 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group
12.09.2023
Nature Publishing Group UK Nature Portfolio |
Subjects | |
Online Access | Get full text |
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Summary: | Abstract
The heart depends on a functional vasculature for oxygenation and transport of nutrients, and it is of interest to learn how primary impairment of the vasculature can indirectly affect cardiac function and heart morphology.
Notch3
-deficiency causes vascular smooth muscle cell (VSMC) loss in the vasculature but the consequences for the heart remain largely elusive. Here, we demonstrate that
Notch3
-/-
mice have enlarged hearts with left ventricular hypertrophy and mild fibrosis. Cardiomyocytes were hypertrophic but not hyperproliferative, and the expression of several cardiomyocyte markers, including
Tnt2
,
Myh6
,
Myh7
and
Actn2,
was altered. Furthermore, expression of genes regulating the metabolic status of the heart was affected: both
Pdk4
and Cd36 were downregulated, indicating a metabolic switch from fatty acid oxidation to glucose consumption.
Notch3
-/-
mice furthermore showed lower liver lipid content.
Notch3
was expressed in heart VSMC and pericytes but not in cardiomyocytes, suggesting that a perturbation of Notch signalling in VSMC and pericytes indirectly impairs the cardiomyocytes. In keeping with this,
Pdgfb
ret/ret
mice, characterized by reduced numbers of VSMC and pericytes, showed left ventricular and cardiomyocyte hypertrophy. In conclusion, we demonstrate that reduced Notch3 or PDGFB signalling in vascular mural cells leads to cardiomyocyte dysfunction. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2045-2322 2045-2322 |
DOI: | 10.1038/s41598-023-42010-7 |