Department of Nephrology, Heping Hospital Affiliated to Changzhi Medical College, No.110, Yanan Road South, Changzhi, Shanxi, China.
Department of Foreign Language Teaching, Changzhi Medical College, No.161, Jiefang East Street, Changzhi, Shanxi, China.
BMC Cardiovasc Disord. 2023 Sep 11;23(1):446. doi: 10.1186/s12872-023-03485-4.
Endothelial progenitor cells (EPCs) transplantation is one of the effective therapies for neointima associated with endothelial injury. Diabetes impairs the function of EPCs and cumbers neointima prevention of EPC transplantation with an ambiguous mechanism. Sodium Tanshinone IIA Sulfonate (STS) is an endothelium-protective drug but whether STS protects EPCs in diabetes is still unknown.
EPCs were treated with High Glucose (HG), STS, and Nucleotide-binding Domain-(NOD) like Receptor 3 (NLRP3), caspase-1, the Receptor of Advanced Glycation End products (AGEs) (RAGE) inhibitors, Thioredoxin-Interacting Protein (TXNIP) siRNA, and EPC proliferation, differentiation functions, and senescence were detected. The treated EPCs were transplanted into db/db mice with the wire-injured Common Carotid Artery (CCA), and the CD31 expression and neointima were detected in the CCA inner wall.
We found that STS inhibited HG-induced expression of NLRP3, the production of active caspase-1 (p20) and mature IL-1β, the expression of catalase (CAT) cleavage, γ-H2AX, and p21 in EPCs. STS restored the expression of Ki67, CD31 and von Willebrand Factor (vWF) in EPCs; AGEs were found in the HG-treated EPCs supernatant, and RAGE blocking inhibited the expression of TXNIP and the production of p20, which was mimicked by STS. STS recovered the expression of CD31 in the wire-injured CCA inner wall and the prevention of neointima in diabetic mice with EPCs transplantation.
STS inhibits the aggravated neointima hyperplasia by protecting the proliferation and differentiation functions of EPC and inhibiting EPC senescence in diabetic mice. The mechanism is related to the preservation of CAT activity by inhibiting the RAGE-TXNIP-NLRP3 inflammasome pathway.
内皮祖细胞（EPCs）移植是治疗内皮损伤相关新生内膜的有效方法之一。糖尿病会损害 EPC 的功能，并且其机制尚不清楚，这给 EPC 移植预防新生内膜形成带来了困难。丹参酮ⅡA 磺酸钠（STS）是一种具有保护血管内皮作用的药物，但 STS 是否能保护糖尿病患者的 EPC 尚不清楚。
用高糖（HG）、STS、核苷酸结合域样受体 3（NLRP3）、半胱氨酸天冬氨酸蛋白酶-1（caspase-1）、晚期糖基化终产物（AGEs）受体（RAGE）抑制剂、硫氧还蛋白相互作用蛋白（TXNIP）siRNA 处理 EPCs，检测 EPC 的增殖、分化功能和衰老情况。将处理后的 EPC 移植到 wire-injured 颈总动脉（CCA）的 db/db 小鼠体内，检测 CCA 内皮层的 CD31 表达和新生内膜。
我们发现 STS 抑制了 HG 诱导的 EPCs 中 NLRP3 的表达、活性 caspase-1（p20）和成熟的 IL-1β的产生、过氧化氢酶（CAT）的裂解、γ-H2AX 和 p21 的表达。STS 恢复了 EPCs 中 Ki67、CD31 和血管性血友病因子（vWF）的表达；在 HG 处理的 EPCs 上清液中发现了 AGEs，RAGE 阻断抑制了 TXNIP 的表达和 p20 的产生，STS 则模拟了这一过程。STS 恢复了 wire-injured CCA 内皮层的 CD31 表达和糖尿病小鼠 EPC 移植对新生内膜的预防作用。
STS 通过保护糖尿病小鼠 EPC 的增殖和分化功能并抑制 EPC 衰老，抑制了 EPC 移植后新生内膜的加重性过度增生。其机制与抑制 RAGE-TXNIP-NLRP3 炎性小体途径来保持 CAT 活性有关。
