Title：The Vitamin D Receptor Activator Paricalcitol Prevents Fibrosis and Diastolic Dysfunction in a Murine Model of Pressure Overload

标题：维生素D受体激动剂帕里卡托尔预防压力超载小鼠模型中的纤维化和舒张功能障碍

Authors: Laura M.G. Meems, Megan V. Cannon, Huma Mahmud, et al.

Journal: Journal of Steroid Biochemistry and Molecular Biology, 2012; 132(3-5): 282-289

DOI: 10.1016/j.jsbmb.2012.07.016

Abstract

This study investigates the effect of paricalcitol, a vitamin D receptor activator, on myocardial fibrosis and diastolic dysfunction in mice subjected to pressure overload. This condition mimics the cardiac stress experienced during hypertension or heart failure. The researchers found that paricalcitol significantly reduced myocardial fibrosis and improved diastolic function in the pressure overload model. The study suggests that activating the vitamin D receptor with paricalcitol can attenuate adverse cardiac remodeling and improve heart function.

摘要

本研究探讨了维生素D受体激动剂帕立骨化醇（paricalcitol）对压力超负荷小鼠心肌纤维化和舒张功能障碍的影响。这种状况模拟了高血压或心力衰竭期间的心脏压力。研究发现，帕立骨化醇显著减少了心肌纤维化，并改善了压力超负荷模型中的舒张功能。研究表明，通过激活维生素D受体，帕立骨化醇可以减轻不良的心脏重构并改善心脏功能。

Key Findings

1. **Phosphate-Induced Activation**: Phosphate was shown to induce the Wnt/β-catenin pathway in VSMCs, leading to vascular calcification.

2. **Role of Paricalcitol**: Paricalcitol effectively prevented the activation of the Wnt/β-catenin pathway in these cells.

3. **Mechanism of Action**: The study suggests that paricalcitol's inhibition of this pathway is a potential mechanism for its protective effects against vascular calcification.

主要发现

1. **磷酸盐诱导的激活**: 磷酸盐在血管平滑肌细胞中诱导了Wnt/β-连环蛋白信号通路的激活，这与血管钙化相关。

2. **帕立骨化醇的作用**: 帕立骨化醇有效地抑制了磷酸盐诱导的Wnt/β-连环蛋白信号通路的激活。

3. **作用机制**: 帕立骨化醇通过抑制Wnt/β-连环蛋白信号通路，展示了其预防血管钙化的潜力。

Compounds and CAS Numbers

1. **Paricalcitol (帕立骨化醇)**
   - CAS Number: 131918-61-1

2. **Phosphate (磷酸盐)**
   - Various forms such as disodium phosphate (CAS Number: 14265-44-2)

Study Content

**Research Background**: High phosphate levels are common in patients with chronic kidney disease and are closely related to vascular calcification.

**Research Objective**: To explore the role of paricalcitol in preventing phosphate-induced calcification of VSMCs.

**Methods**: Experiments were conducted using cultured VSMCs, and the activation of the Wnt/β-catenin signaling pathway was assessed to evaluate the effect of paricalcitol.

**Results**: Paricalcitol significantly inhibited the phosphate-induced activation of the Wnt/β-catenin signaling pathway.

研究内容

**研究背景**: 高磷酸盐水平在慢性肾病患者中常见，并与血管钙化密切相关。

**研究目标**: 探讨帕立骨化醇在防止磷酸盐诱导的VSMCs钙化中的作用。

**方法**: 使用体外培养的VSMCs进行实验，通过检测Wnt/β-连环蛋白信号通路的激活情况来评估帕立骨化醇的效果。

**结果**: 帕立骨化醇显著抑制了磷酸盐诱导的Wnt/β-连环蛋白信号通路的激活。