National Clinical Research Center for Geriatrics and Department of Nephrology, West China Hospital, Sichuan University, Chengdu, China.
Department of Nephrology, West China Hospital, Sichuan University, Chengdu, China.
Nephrology (Carlton). 2020 Mar;25(3):264-272. doi: 10.1111/nep.13677. Epub 2019 Nov 24.
Vascular calcification (VC) is a common complication in chronic kidney disease (CKD) and has been shown to be associated with increased cardiovascular events and mortality. This study was to explore the role of Wnt-signaling pathway in CKD VC, and the association between VC and blood pressure variability (BPV) which is a risk factor of cardiovascular events.
Adult male Sprague-Dawley rats were divided into adenine-induced CKD group (n = 5), 5/6 nephrectomy CKD group (n = 5), sham group (n = 5) and control group (n = 5). Low-calcium-high-phosphate diets were introduced to induce vascular calcification. Both daytime (hour-to-hour during the day) and mid-term (day-to-day for 9 days) blood pressure (BP) were collected and analyzed for BPV metrics. At sacrifice, kidney, heart and aorta samples were taken for histological analyses. Calcium deposition in aorta was identified with Alizarin Red stain and graded. Immunohistochemistry stain and western blot were performed for Wnt3a, Wnt5a, β-catenin, sclerostin, osteopontin, and α-SMA.
Compared with control rats, CKD rats suffered from markedly severer VC (Grade 2.6 ± 0.2 and 1.8 ± 0.8 vs 0.0 ± 0.0 and 0.2 ± 0.4, P = .0010). VC was positively correlated with vascular Wnt3a and β-catenin expression (P = .0032 and .0000), but not significantly associated with Wnta5a or sclerostin. Besides, CKD rats showed increased BPV (P < .001), which was also positively correlated with VC.
We confirmed that CKD rats had enhanced Wnt-signaling in vascular tissue and severer aorta calcification together with increased BPV. Wnt pathway may be a potential target in future VC and BPV management in CKD.
血管钙化（VC）是慢性肾脏病（CKD）的常见并发症，已被证明与心血管事件和死亡率的增加有关。本研究旨在探讨 Wnt 信号通路在 CKD 血管钙化中的作用，以及血管钙化与血压变异性（BPV）的关系，BPV 是心血管事件的一个危险因素。
成年雄性 Sprague-Dawley 大鼠分为腺嘌呤诱导的 CKD 组（n = 5）、5/6 肾切除术 CKD 组（n = 5）、假手术组（n = 5）和对照组（n = 5）。给予低钙高磷饮食诱导血管钙化。采集并分析日间（白天每小时）和中期（9 天内每天）血压（BP）以评估 BPV 指标。处死时，取肾脏、心脏和主动脉样本进行组织学分析。用茜素红染色鉴定主动脉钙沉积并分级。进行 Wnt3a、Wnt5a、β-连环蛋白、骨硬化蛋白、骨桥蛋白和α-SMA 的免疫组化染色和 Western blot。
与对照组大鼠相比，CKD 大鼠的 VC 明显更严重（2.6±0.2 级和 1.8±0.8 级 vs 0.0±0.0 级和 0.2±0.4 级，P =.0010）。VC 与血管 Wnt3a 和 β-连环蛋白表达呈正相关（P =.0032 和.0000），但与 Wnta5a 或骨硬化蛋白无明显相关性。此外，CKD 大鼠的 BPV 增加（P < .001），且与 VC 呈正相关。
我们证实 CKD 大鼠的血管组织中 Wnt 信号增强，主动脉钙化更严重，BPV 增加。Wnt 通路可能是未来 CKD 血管钙化和 BPV 管理的潜在靶点。
