Department of Blood Purification, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Gongti South Road, Chaoyang District, Beijing, 100020, China.
BMC Nephrol. 2020 Dec 4;21(1):527. doi: 10.1186/s12882-020-02183-z.
Hydrogen sulfide (HS) has been shown to inhibit the atherosclerosis development and progression. It is produced by cystathionine γ-lyase (CSE) in the cardiovascular system. In our previous study, it has been shown that CSE/HS system plays a significant role in the changes of uremic accelerated atherosclerosis (UAAS), but the mechanism is not known clearly.
In this study, we explored the antagonism of CSE/HS system in UAAS and identified its possible signaling molecules in ApoE mice with 5/6 nephrectomy and fed with atherogenic diet. Mice were divided into sham operation group (sham group), UAAS group, sodium hydrosulfide group (UAAS+NaHS group) and propargylglycine group (UAAS+PPG group). Serum creatinine, urea nitrogen, lipid levels and lesion size of atherosclerotic plaque in the aortic roots were analyzed. Meanwhile, the expression of CSE, TGF-β and phosphorylation of Smad3 were detected.
Compared with sham group, the aortic root of ApoE mice in the UAAS group developed early atherosclerosis, the levels of total cholesterol, triglyceride, low-density lipoprotein-cholesterol, serum creatinine and urea nitrogen were also higher than that in the sham group. NaHS administration can inhibit the development of atherosclerosis, but PPG administration can accelerate the atherosclerosis development. Meanwhile, the protein expression levels of CSE and TGF-β and phosphorylation of Smad3 significantly decreased in the UAAS mice. Treatment of UAAS mice with NaHS inhibited TGF-β protein expression and Smad3 phosphorylation decrease, but PPG treatment had the opposite effect.
The CSE/HS system is of great importance for treating atherosclerosis in patients with chronic kidney disease, and it may protect the vascular from atherosclerosis through the TGF-β/Smad pathway.
硫化氢（HS）已被证明可抑制动脉粥样硬化的发展和进展。它是由心血管系统中的胱硫醚 γ-裂解酶（CSE）产生的。在我们之前的研究中，已经表明 CSE/HS 系统在尿毒症加速动脉粥样硬化（UAAS）的变化中起着重要作用，但机制尚不清楚。
在这项研究中，我们探讨了 CSE/HS 系统在 UAAS 中的拮抗作用，并在接受 5/6 肾切除术和致动脉粥样硬化饮食喂养的 ApoE 小鼠中鉴定了其可能的信号分子。将小鼠分为假手术组（sham 组）、UAAS 组、硫氢化钠组（UAAS+NaHS 组）和炔丙基甘氨酸组（UAAS+PPG 组）。分析血清肌酐、尿素氮、血脂水平和主动脉根部粥样硬化斑块的病变大小。同时，检测 CSE、TGF-β 和 Smad3 磷酸化的表达。
与 sham 组相比，UAAS 组的 ApoE 小鼠主动脉根部发生早期动脉粥样硬化，总胆固醇、甘油三酯、低密度脂蛋白胆固醇、血清肌酐和尿素氮水平也高于 sham 组。NaHS 给药可抑制动脉粥样硬化的发展，但 PPG 给药可加速动脉粥样硬化的发展。同时，UAAS 小鼠的 CSE 和 TGF-β 蛋白表达及 Smad3 磷酸化水平显著降低。UAAS 小鼠给予 NaHS 可抑制 TGF-β 蛋白表达和 Smad3 磷酸化减少，但 PPG 处理则相反。
CSE/HS 系统对治疗慢性肾脏病患者的动脉粥样硬化具有重要意义，它可能通过 TGF-β/Smad 途径保护血管免受动脉粥样硬化的侵害。
