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Cx47 fine-tunes the handling of serum lipids but is dispensable for lymphatic vascular function.
- Source :
-
PloS one [PLoS One] 2017 Jul 21; Vol. 12 (7), pp. e0181476. Date of Electronic Publication: 2017 Jul 21 (Print Publication: 2017). - Publication Year :
- 2017
-
Abstract
- Mutations in the gap junction protein connexin47 (Cx47) are associated with lymphedema. However, the role of Cx47 in lymphatic pathophysiology is unknown. We demonstrate that Cx47 is expressed in lymphatic endothelial cells by whole-mount immunostaining and qPCR. To determine if Cx47 plays a role in lymphatic vessel function we analysed Cx47-/- mice. Cx47-deficiency did not affect lymphatic contractility (contractile amplitude or frequency) or lymphatic morphology (vessel diameter or number of valves). Interstitial fluid drainage or dendritic cell migration through lymphatic vessels was also not affected by Cx47-deficiency. Cx47 is dispensable for long-chain fatty acid absorption from the gut but rather promotes serum lipid handling as prolonged elevated triglyceride levels were observed in Cx47-deficient mice after oral lipid tolerance tests. When crossed with Apolipoprotein E-deficient (Apoe-/-) mice, LDL-cholesterol was decreased in young Cx47-/-Apoe-/- adults as compared to Apoe-/- mice, which was inverted later in life. Finally, advanced atherosclerotic plaques in thoracic-abdominal aortas of 15 months-old mice tended to be larger in Cx47-/-Apoe-/- mice. These plaques contained fewer macrophages but similar amounts of T lymphocytes, collagen and lipids than plaques of Apoe-/- mice. In conclusion, Cx47 is expressed in lymphatic endothelium and seems modestly implicated in multiple aspects of lymphatic pathophysiology.
- Subjects :
- Aging metabolism
Aging pathology
Animals
Apolipoproteins E genetics
Apolipoproteins E metabolism
Atherosclerosis pathology
Cell Movement physiology
Collagen metabolism
Connexins genetics
Dendritic Cells metabolism
Dendritic Cells pathology
Diet, High-Fat
Disease Models, Animal
Endothelial Cells pathology
Fatty Acids metabolism
Lymphatic Vessels pathology
Macrophages metabolism
Macrophages pathology
Mice, Inbred C57BL
Mice, Knockout
T-Lymphocytes metabolism
T-Lymphocytes pathology
Atherosclerosis metabolism
Cholesterol, LDL blood
Connexins metabolism
Endothelial Cells metabolism
Lymphatic Vessels metabolism
Triglycerides blood
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 12
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 28732089
- Full Text :
- https://doi.org/10.1371/journal.pone.0181476