Differential effect of basal vitamin D status in monocrotaline induced pulmonary arterial hypertension in normal and vitamin D deficient rats : Possible involvement of eNOS/TGF-β/α-SMA signaling pathways
Copyright © 2022 Elsevier Inc. All rights reserved..
Vitamin D deficiency is common and linked to poor prognosis in pulmonary arterial hypertension (PAH). We investigated the differential effect of basal vitamin D levels in monocrotaline (MCT) induced PAH in normal and vitamin D deficient (VDD) rats. Rats were fed a VDD diet and exposed to filtered fluorescent light to deplete vitamin D. Normal rats were pretreated with vitamin D 100 IU/d and treated with vitamin D 100 and 200 IU/d, while VDD rats received vitamin D 100 IU/d. Vitamin D receptor (VDR) silencing was done in human umbilical vein endothelial cells (HUVECs) using VDR siRNA. Calcitriol (50 nM/mL) was added to human pulmonary artery smooth muscle cells (HPASMCs) and HUVECs before and after the exposure to TGF-β (10 ng/mL). Vitamin D 100 IU/d pretreatment in normal rats up-regulated the expression of eNOS and inhibited endothelial to mesenchymal transition significantly and maximally. Vitamin D 100 IU/d treatment in VDD rats was comparable to vitamin D 200 IU/d treated normal rats. These effects were significantly attenuated by L-NAME (20 mg/kg), a potent eNOS inhibitor. Exposure to TGF- β significantly reduced the expression of eNOS and increased the mesenchymal marker expression in normal and VDR-silenced HUVECs and HPASMCs, which were averted by treatment and maximally inhibited by pretreatment with calcitriol (50 nM). To conclude, this study provided novel evidence suggesting the beneficial role of higher basal vitamin D levels, which are inversely linked with PAH severity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:113 |
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| Enthalten in: |
The Journal of nutritional biochemistry - 113(2023) vom: 25. März, Seite 109246 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shah, Sadia [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.02.2023 Date Revised 08.03.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jnutbio.2022.109246 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM350082707 |
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| 100 | 1 | |a Shah, Sadia |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Differential effect of basal vitamin D status in monocrotaline induced pulmonary arterial hypertension in normal and vitamin D deficient rats |b Possible involvement of eNOS/TGF-β/α-SMA signaling pathways |
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| 500 | |a Date Revised 08.03.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 Elsevier Inc. All rights reserved. | ||
| 520 | |a Vitamin D deficiency is common and linked to poor prognosis in pulmonary arterial hypertension (PAH). We investigated the differential effect of basal vitamin D levels in monocrotaline (MCT) induced PAH in normal and vitamin D deficient (VDD) rats. Rats were fed a VDD diet and exposed to filtered fluorescent light to deplete vitamin D. Normal rats were pretreated with vitamin D 100 IU/d and treated with vitamin D 100 and 200 IU/d, while VDD rats received vitamin D 100 IU/d. Vitamin D receptor (VDR) silencing was done in human umbilical vein endothelial cells (HUVECs) using VDR siRNA. Calcitriol (50 nM/mL) was added to human pulmonary artery smooth muscle cells (HPASMCs) and HUVECs before and after the exposure to TGF-β (10 ng/mL). Vitamin D 100 IU/d pretreatment in normal rats up-regulated the expression of eNOS and inhibited endothelial to mesenchymal transition significantly and maximally. Vitamin D 100 IU/d treatment in VDD rats was comparable to vitamin D 200 IU/d treated normal rats. These effects were significantly attenuated by L-NAME (20 mg/kg), a potent eNOS inhibitor. Exposure to TGF- β significantly reduced the expression of eNOS and increased the mesenchymal marker expression in normal and VDR-silenced HUVECs and HPASMCs, which were averted by treatment and maximally inhibited by pretreatment with calcitriol (50 nM). To conclude, this study provided novel evidence suggesting the beneficial role of higher basal vitamin D levels, which are inversely linked with PAH severity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Endothelial to mesenchymal transition | |
| 650 | 4 | |a Pulmonary arterial hypertension | |
| 650 | 4 | |a Right ventricular systolic pressure | |
| 650 | 4 | |a Vitamin D deficiency | |
| 650 | 4 | |a Vitamin D supplement | |
| 650 | 7 | |a Monocrotaline |2 NLM | |
| 650 | 7 | |a 73077K8HYV |2 NLM | |
| 650 | 7 | |a Vitamin D |2 NLM | |
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| 650 | 7 | |a Vitamins |2 NLM | |
| 650 | 7 | |a Transforming Growth Factor beta |2 NLM | |
| 700 | 1 | |a Vishwakarma, Vishal Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Arava, Sudheer Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Mridha, Asit Ranjan |e verfasserin |4 aut | |
| 700 | 1 | |a Yadav, Raj Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Seth, Sandeep |e verfasserin |4 aut | |
| 700 | 1 | |a Bhatia, Jagriti |e verfasserin |4 aut | |
| 700 | 1 | |a Hote, Milind P |e verfasserin |4 aut | |
| 700 | 1 | |a Arya, Dharamvir Singh |e verfasserin |4 aut | |
| 700 | 1 | |a Yadav, Harlokesh Narayan |e verfasserin |4 aut | |
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