Laboratory of Pathophysiology, University of Antwerp, Wilrijk, Belgium.
Laboratory of Physiopharmacology, University of Antwerp, Wilrijk, Belgium.
Nephrol Dial Transplant. 2023 May 4;38(5):1127-1138. doi: 10.1093/ndt/gfac301.
Cardiovascular disease remains the leading cause of death in chronic kidney disease (CKD) patients, especially in those undergoing dialysis and kidney transplant surgery. CKD patients are at high risk of developing arterial media calcifications (AMC) and arterial stiffness. We hypothesized that investigation of disease progression at an early stage could provide novel insights in understanding AMC etiology.
An adenine diet was administered to male Wistar rats to induce AMC. Rats were sacrificed after 2, 4 and 8 weeks. AMC was measured by assessment of aortic calcium and visualized using histology. Arterial stiffness was measured in vivo by ultrasound and ex vivo by applying cyclic stretch of physiological magnitude on isolated arterial segments, allowing us to generate the corresponding pressure-diameter loops. Further, ex vivo arterial reactivity was assessed in organ baths at 2 and 4 weeks to investigate early alterations in biomechanics/cellular functionality.
CKD rats showed a time-dependent increase in aortic calcium which was confirmed on histology. Accordingly, ex vivo arterial stiffness progressively worsened. Pressure-diameter loops showed a gradual loss of arterial compliance in CKD rats. Additionally, viscoelastic properties of isolated arterial segments were altered in CKD rats. Furthermore, after 2 and 4 weeks of adenine treatment, a progressive loss in basal, nitric oxide (NO) levels was observed, which was linked to an increased vessel tonus and translates into an increasing viscous modulus.
Our observations indicate that AMC-related vascular alterations develop early after CKD induction prior to media calcifications being present. Preventive action, related to restoration of NO bioavailability, might combat AMC development.
心血管疾病仍然是慢性肾脏病（CKD）患者死亡的主要原因，尤其是在接受透析和肾移植手术的患者中。CKD 患者发生动脉中层钙化（AMC）和动脉僵硬的风险较高。我们假设在早期阶段研究疾病进展可以为理解 AMC 的病因提供新的见解。
给予雄性 Wistar 大鼠腺嘌呤饮食以诱导 AMC。大鼠在 2、4 和 8 周后被处死。通过评估主动脉钙来测量 AMC，并通过组织学可视化。通过超声在体内测量动脉僵硬，通过对分离的动脉段施加生理幅度的循环拉伸在体外测量，使我们能够生成相应的压力-直径环。此外，在 2 和 4 周时在器官浴中评估离体动脉反应性，以研究生物力学/细胞功能的早期变化。
CKD 大鼠的主动脉钙呈时间依赖性增加，组织学证实了这一点。相应地，体外动脉僵硬逐渐恶化。压力-直径环显示 CKD 大鼠的动脉顺应性逐渐丧失。此外，在 CKD 大鼠中，分离的动脉段的粘弹性特性发生改变。此外，在腺嘌呤治疗 2 和 4 周后，观察到基础一氧化氮（NO）水平逐渐降低，这与血管张力增加有关，并转化为粘性模量增加。
我们的观察结果表明，在 AMC 相关血管改变发生在中层钙化之前，在 CKD 诱导后早期就已经发生。与恢复 NO 生物利用度相关的预防措施可能会对抗 AMC 的发展。
