Arterial klotho expression and FGF23 effects on vascular calcification and function.
Recent studies support a role for FGF23 and its co-receptor Klotho in cardiovascular pathology, yet the underlying mechanisms remain largely elusive. Herein, we analyzed the expression of Klotho in mouse arteries and generated a novel mouse model harboring a vascular smooth muscle cell specific dele...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3618102?pdf=render |
| _version_ | 1818684019400769536 |
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| author | Karolina Lindberg Hannes Olauson Risul Amin Arvind Ponnusamy Regina Goetz Rebecca F Taylor Moosa Mohammadi Ann Canfield Karolina Kublickiene Tobias E Larsson |
| author_facet | Karolina Lindberg Hannes Olauson Risul Amin Arvind Ponnusamy Regina Goetz Rebecca F Taylor Moosa Mohammadi Ann Canfield Karolina Kublickiene Tobias E Larsson |
| author_sort | Karolina Lindberg |
| collection | DOAJ |
| description | Recent studies support a role for FGF23 and its co-receptor Klotho in cardiovascular pathology, yet the underlying mechanisms remain largely elusive. Herein, we analyzed the expression of Klotho in mouse arteries and generated a novel mouse model harboring a vascular smooth muscle cell specific deletion of Klotho (Sm22-KL(-/-) ). Arterial Klotho expression was detected at very low levels with quantitative real-time PCR; Klotho protein levels were undetectable by immunohistochemistry and Western blot. There was no difference in arterial Klotho between Sm22-KL(-/-) and wild-type mice, as well as no changes in serum markers of mineral metabolism. Intravenous delivery of FGF23 elicited a rise in renal (0.005; p<0.01) but not arterial Egr-1 expression, a marker of Klotho-dependent FGF23 signaling. Further, the impact of FGF23 on vascular calcification and endothelial response was evaluated in bovine vascular smooth muscle cells (bVSMC) and in a murine ex vivo model of endothelial function, respectively. FGF23 treatment (0.125-2 ng/mL) did not modify calcification in bVSMCs or dilatory, contractile and structural properties in mice arterial specimen ex vivo. Collectively, these results demonstrate that FGF23-Klotho signaling is absent in mouse arteries and that the vascular response was unaffected by FGF23 treatment. Thus, our data do not support Klotho-mediated FGF23 effects in the vasculature although confirmative studies in humans are warranted. |
| first_indexed | 2024-12-17T10:43:58Z |
| format | Article |
| id | doaj.art-2c3e4060d78a46f98c1066ca1813ecc6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T10:43:58Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2c3e4060d78a46f98c1066ca1813ecc62022-12-21T21:52:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0184e6065810.1371/journal.pone.0060658Arterial klotho expression and FGF23 effects on vascular calcification and function.Karolina LindbergHannes OlausonRisul AminArvind PonnusamyRegina GoetzRebecca F TaylorMoosa MohammadiAnn CanfieldKarolina KublickieneTobias E LarssonRecent studies support a role for FGF23 and its co-receptor Klotho in cardiovascular pathology, yet the underlying mechanisms remain largely elusive. Herein, we analyzed the expression of Klotho in mouse arteries and generated a novel mouse model harboring a vascular smooth muscle cell specific deletion of Klotho (Sm22-KL(-/-) ). Arterial Klotho expression was detected at very low levels with quantitative real-time PCR; Klotho protein levels were undetectable by immunohistochemistry and Western blot. There was no difference in arterial Klotho between Sm22-KL(-/-) and wild-type mice, as well as no changes in serum markers of mineral metabolism. Intravenous delivery of FGF23 elicited a rise in renal (0.005; p<0.01) but not arterial Egr-1 expression, a marker of Klotho-dependent FGF23 signaling. Further, the impact of FGF23 on vascular calcification and endothelial response was evaluated in bovine vascular smooth muscle cells (bVSMC) and in a murine ex vivo model of endothelial function, respectively. FGF23 treatment (0.125-2 ng/mL) did not modify calcification in bVSMCs or dilatory, contractile and structural properties in mice arterial specimen ex vivo. Collectively, these results demonstrate that FGF23-Klotho signaling is absent in mouse arteries and that the vascular response was unaffected by FGF23 treatment. Thus, our data do not support Klotho-mediated FGF23 effects in the vasculature although confirmative studies in humans are warranted.http://europepmc.org/articles/PMC3618102?pdf=render |
| spellingShingle | Karolina Lindberg Hannes Olauson Risul Amin Arvind Ponnusamy Regina Goetz Rebecca F Taylor Moosa Mohammadi Ann Canfield Karolina Kublickiene Tobias E Larsson Arterial klotho expression and FGF23 effects on vascular calcification and function. PLoS ONE |
| title | Arterial klotho expression and FGF23 effects on vascular calcification and function. |
| title_full | Arterial klotho expression and FGF23 effects on vascular calcification and function. |
| title_fullStr | Arterial klotho expression and FGF23 effects on vascular calcification and function. |
| title_full_unstemmed | Arterial klotho expression and FGF23 effects on vascular calcification and function. |
| title_short | Arterial klotho expression and FGF23 effects on vascular calcification and function. |
| title_sort | arterial klotho expression and fgf23 effects on vascular calcification and function |
| url | http://europepmc.org/articles/PMC3618102?pdf=render |
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