Tanaka Hiroaki, Kataoka Masaharu, Isobe Sarasa, Yamamoto Tsunehisa, Shirakawa Kohsuke, Endo Jin, Satoh Toru, Hakamata Yoji, Kobayashi Eiji, Sano Motoaki, Fukuda Keiichi
Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
Actelion Pharmaceuticals Japan Ltd., Tokyo, Japan.
PLoS One. 2017 Jul 7;12(7):e0180615. doi: 10.1371/journal.pone.0180615. eCollection 2017.
Pulmonary 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.
Serum 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.
The 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.
Vitamin 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.
由肺血管阻力升高引起的肺动脉高压(PH)会导致右心衰竭并最终导致死亡。维生素D缺乏会使个体易患高血压和左心室功能障碍;然而,血清维生素D水平与PH及右心室(RV)功能障碍之间的关系仍不清楚。
评估PH患者的血清25-羟维生素D [25(OH)D]水平与疾病严重程度的相关性。为了研究补充维生素D是否可以预防PH患者肺血管重塑和RV功能障碍的发展,给PH大鼠模型喂食普通饲料或高维生素D饮食。
大多数(95.1%)PH患者的25(OH)D水平处于不足范围,这与PH患者平均肺动脉压升高、肺血管阻力增加和心输出量降低有关。补充维生素D可显著提高PH大鼠的血清25(OH)D水平并改善其存活率。有趣的是,虽然补充维生素D的大鼠肌肉型肺动脉中层厚度和RV收缩压仍有典型升高,但RV心肌细胞肥大和B型利钠肽表达显著减弱。
在诊断为PH的患者中经常发现维生素D缺乏,血清25(OH)D水平低与PH和RV功能障碍的严重程度有关。在PH大鼠中补充维生素D可通过改善病理性RV肥大来提高存活率。这些发现表明维生素D摄入不足可能会加速RV功能障碍,从而导致补充维生素D对PH具有关键的临床影响。