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

Shah, Sadia; Vishwakarma, Vishal Kumar; Arava, Sudhir; Mridha, Asit Ranjan; Yadav, Raj Kumar; Seth, Sandeep; Bhatia, Jagriti; Hote, Milind Padmakar; Arya, Dharamvir Singh; Yadav, Harlokesh Narayan

doi:10.1016/j.jnutbio.2022.109246

Cited by 6 publications

(8 citation statements)

References 53 publications

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“…Increasing vitamin D levels can promote the expression of KCNK3 and the activity of TASK‐1 channels, which may be targets for the treatment of PH 39,41,42 . Although restoring vitamin D levels cannot reduce the pulmonary artery pressure, it can improve the prognosis and some pathological changes in PH 41,43 . Therefore, supplementing with vitamin D has clinical benefits for PH patients.…”

Section: Discussionmentioning

confidence: 99%

An inverse causal relationship between serum 25‐hydroxyvitamin D levels and pulmonary hypertension: A two‐sample Mendelian randomization study

Chao,

Wang,

Mei

et al. 2024

Pulm. circ.

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Observational studies have confirmed that 25‐hydroxyvitamin D (25(OH)D) is associated with pulmonary hypertension (PH), but the causal association between each other is unclear. Therefore, Mendelian randomization (MR) method was performed to validate the causal association between PH and serum 25(OH)D levels. The summary data for 25(OH)D and PH were from the National Human Genome Research Institute‐European Bioinformatics Institute. Catalog of human genome‐wide association studies and FinnGen biobank consortium. MR analysis was utilized to explore the potential causal association between PH and 25(OH)D. To evaluate this association, inverse variance weighting was considered as the primary method. Cochran's Q test, MR‐Egger intercept test, and “leave‐one‐out” sensitivity analyses were utilized to control the pleiotropy and heterogeneity in the study. Two‐sample MR analysis revealed an inverse causal relationship between 25(OH)D and PH (odds ratio: 0.376, 95% confidence interval: 0.162–0.876, p = 2.334 × 10−2). There was no significant heterogeneity and pleiotropy. The present study confirmed the inverse causal relationship between 25(OH)D and PH. This pathway may provide another treatment pathway in PH. Further studies to elucidate this pathway is indicated.

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Section: Discussionmentioning

confidence: 99%

An inverse causal relationship between serum 25‐hydroxyvitamin D levels and pulmonary hypertension: A two‐sample Mendelian randomization study

Chao,

Wang,

Mei

et al. 2024

Pulm. circ.

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“…We used the model of MCT-induced PH that was already established in our laboratory and well documented. 4 In the current study, we used MCT-induced PH in rats manifested by rise in right ventricular pressure, right ventricular hypertrophy, and increased expressions of TGF-b R1 and a-SMA. However, the eNOS expression was observed to be decreased with an oxidative stress marker.…”

Section: Discussionmentioning

confidence: 99%

“…We used the model of MCT-induced PH that was already established in our laboratory and well documented. 4…”

Section: Discussionmentioning

confidence: 99%

“…The right ventricle was dissected and measurement of the right ventricular tissue was performed by an already well-established procedure in our laboratory. 4 Briefly, the heart and lung tissues were isolated after performing a thoracotomy. Both the atria were removed and then left ventricle with interventricular septum was separated from right ventricle.…”

Section: Methodsmentioning

confidence: 99%

“…15,16 MCT was dissolved in 1 N HCl at pH 7.4 after this solution was mixed with distilled water and administered subcutaneous injection as a single dose of 50 mg/kg to animals. 4,17…”

Section: Induction Of Pahmentioning

confidence: 99%

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Effect of Benidipine Alone and in Combination With Bosentan and Sildenafil in Amelioration of Pulmonary Arterial Hypertension in Experimental Model in Rats

Kumari,

Vishwakarma,

Kumar

et al. 2024

Journal of Cardiovascular Pharmacology

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Pulmonary arterial hypertension (PAH) is a persistent condition affecting the pulmonary arteries' endothelium. Benidipine, a calcium channel blocker, possesses vasodilatory, anti-inflammatory activity, reduces oxidative stress, and inhibits the activity of TGF-β receptor 1 and α-SMA. The present study was designed to investigate the effect of benidipine alone and in combination with bosentan and sildenafil on monocrotaline (MCT)-induced pulmonary hypertension (PH) in a rat model. PAH was induced by single-dose administration of MCT in rats. Animals were randomized into different groups and treated with benidipine alone and in combination with bosentan or sildenafil. Various parameters such as hemodynamic parameters, Fulton's index, oxidative stress parameters, and inflammatory markers were performed. Additionally, histopathology of lung and right ventricular tissue, immunohistochemistry, expression of α-SMA, eNOS, TGF- β, and RT-PCR, and an in-vitro (using HUVECs) study were also carried out. Treatment of benidipine and its combination exhibited better prevention in the elevated right ventricular systolic pressure, right ventricular hypertrophy, rise in oxidative stress and increase in expression of α-SMA and TGF-β receptor 1 compared to MCT control group rats. In HUVEC’s cells, the expression of α-SMA was increased, whereas eNOS decreased after TGF-β exposure and was substantially reversed after pre-treatment with benidipine. We concluded that benidipine and its combination with bosentan and sildenafil exhibit beneficial effects in MCT-induced PAH through the α-SMA/TGF-β/eNOS signaling pathway.

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Unveiling the Link of Vitamin D and Diverse Cardiovascular Disorders: Current Status and Future Prospective

Kumar,

Chhabra,

Vishwakarma

et al. 2024

Advances in Biochemistry in Health and Disease

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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

Cited by 6 publications

References 53 publications

An inverse causal relationship between serum 25‐hydroxyvitamin D levels and pulmonary hypertension: A two‐sample Mendelian randomization study

An inverse causal relationship between serum 25‐hydroxyvitamin D levels and pulmonary hypertension: A two‐sample Mendelian randomization study

Effect of Benidipine Alone and in Combination With Bosentan and Sildenafil in Amelioration of Pulmonary Arterial Hypertension in Experimental Model in Rats

Unveiling the Link of Vitamin D and Diverse Cardiovascular Disorders: Current Status and Future Prospective

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