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Abstract：
This study aims to investigate the impact of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) on vascular calcification in rats. The rationale behind studying ENPP1\'s role in vascular calcification lies in its potential to modulate calcification processes. Understanding this relationship can offer insights into novel therapeutic avenues for addressing vascular calcification-related disorders. In this experiment, vascular smooth muscle cell (VSMC) calcification was induced using β-glycerophosphoric acid. Subsequently, recombinant AAV9-carrying ENPP1 was introduced into VSMCs to achieve both in vitro and in vivo overexpression of ENPP1. The findings indicate that ENPP1 overexpression significantly reduces calcium and phosphorus content in the aorta (P < 0.05). Alizarin red and von Kossa staining reveal notable reductions in calcium salt deposits in VSMCs and aorta, respectively. Notably, the expression levels of BMP-2, PINP, OC, and BALP were substantially decreased in VSMCs (P < 0.05), underscoring ENPP1\'s role in impeding osteoblast-like transdifferentiation of VSMCs. Additionally, ENPP1 overexpression led to a significant increase in pyrophosphate (PPi) levels compared to control rats (P < 0.05). In conclusion, this study suggests that ENPP1 contributes to alleviating vascular calcification by elevating PPi levels and inhibiting the phenotypic transformation of VSMCs. These findings shed light on the potential therapeutic role of ENPP1 in mitigating vascular calcification-related complications.
摘要：
本研究旨在探讨外核苷酸焦磷酸酶/磷酸二酯酶1(ENPP1)对大鼠血管钙化的影响。研究ENPP1在血管钙化中的作用的基本原理在于其调节钙化过程的潜力。了解这种关系可以为解决血管钙化相关疾病的新治疗途径提供见解。在这个实验中,β-甘油磷酸诱导血管平滑肌细胞(VSMC)钙化。随后，将携带ENPP1的重组AAV9导入VSMC以实现ENPP1的体外和体内过表达。结果表明，ENPP1过表达显著降低了主动脉中钙和磷的含量（P<0.05）。茜素红和vonKossa染色显示VSMC和主动脉中钙盐沉积显着减少，分别。值得注意的是,BMP-2，PINP的表达水平，OC,VSMC和BALP显著下降(P<0.05)，强调ENPP1在阻碍VSMCs成骨细胞样转分化中的作用。此外,与对照大鼠相比,ENPP1过表达导致焦磷酸盐(PPi)水平显著增加(P<0.05)。总之,本研究提示ENPP1通过升高PPi水平和抑制VSMC的表型转化,有助于缓解血管钙化.这些发现揭示了ENPP1在减轻血管钙化相关并发症方面的潜在治疗作用。
