Therapeutic impact of dietary vitamin D supplementation for preventing right ventricular remodeling and improving survival in pulmonary hypertension

Abstract

BackgroundPulmonary hypertension (PH), caused by elevated pulmonary vascular resistance, leads to right heart failure and ultimately death. Vitamin D deficiency can predispose individuals to hypertension and left ventricular dysfunction; however, it remains unknown how serum vitamin D level is related to PH and right ventricular (RV) dysfunction.MethodsSerum 25-hydroxyvitamin D [25(OH)D] levels were assessed in PH patients for an association with disease severity. To examine whether vitamin D supplementation could prevent the development of pulmonary vascular remodeling and RV dysfunction in PH, a rat model of PH was fed either normal chow or a high vitamin D diet.ResultsThe majority (95.1%) of PH patients had 25(OH)D levels in the insufficiency range, which is associated with increased mean pulmonary artery pressure, increased pulmonary vascular resistance, and decreased cardiac output in PH patients. Vitamin D supplementation significantly increased serum 25(OH)D levels and improved survival in PH rats. Interestingly, while the supplemented rats retained the typical increases in medial thickness of the muscular pulmonary arteries and RV systolic pressure, RV cardiomyocyte hypertrophy and B-type natriuretic peptide expression was significantly attenuated.ConclusionsVitamin D deficiency is frequently seen in patients diagnosed with PH and low serum levels of 25(OH)D are associated with severity of PH and RV dysfunction. Vitamin D supplementation in PH rats improved survival via ameliorating pathological RV hypertrophy. These findings suggest an insufficient intake of vitamin D might potentially accelerate RV dysfunction, leading to a crucial clinical impact of vitamin D supplementation in PH.

Total, Bioavailable, and Free Vitamin D Levels and Their Prognostic Value in Pulmonary Arterial Hypertension

“…Preliminary epidemiological studies suggested that vitD deficiency is more prevalent in PAH than in the general population. In fact, in our PAH cohort (n = 67), severe vitD deficiency was very common (median 7.17 ng/mL), in concordance with previous reports in small series (n = 22, 19, and 12) [23,24,26]. Values were very similar for idiopathic (class 1.1) and heritable PAH (class 1.2), and the sample of the drug-induced PAH (class 1.3) was too small to draw any conclusion.…”

“…Tanaka et al (23) also reported that total 25(OH)vitD levels negatively correlated with mPAP assessed by right-heart catheterization, with a significant positive correlation with cardiac output. According to the ESC/ERS guidelines for the diagnosis and treatment of PH and the World Health Organization [4], there are several factors that provide prognostic information and may be used to guide therapeutic decisions.…”

“…Some preliminary evidence suggests that vitD deficiency is common in PAH [23][24][25][26]. Herein, we aimed to examine the total, bioavailable, and free 25(OH)vitD levels and their relationship with relevant clinical variables in PAH.…”

Impact of Nutrition on Pulmonary Arterial Hypertension

“…To clarify whether vitamin D levels could be involved in PAH progression, Tanaka et al treated PAH rats with a diet containing 10;000 UI/kg of cholecalciferol [59]. Notably, in this study, they found that vitamin D supplementation in PAH rats improved survival and attenuated some typical features in PAH such as right ventricle remodeling, assessed by Fulton index (ratio of right ventricle weight to left ventricle plus septum weight), and medial thickness of muscular pulmonary arteries.…”

“…Notably, in this study, they found that vitamin D supplementation in PAH rats improved survival and attenuated some typical features in PAH such as right ventricle remodeling, assessed by Fulton index (ratio of right ventricle weight to left ventricle plus septum weight), and medial thickness of muscular pulmonary arteries. Despite these benefits of vitamin D, cholecalciferol treatment did not decrease pulmonary artery pressure [59]. Moreover, in an in vitro setup, calcitriol treatment inhibited the hypoxia-induced proliferation and migration in rat pulmonary artery endothelial cells (PAEC) via miR-204/TGFβ/Smad signaling pathway.…”