Xu Hong, Xu Rui, Yan Kaixin, Bu Juan
Gerontology Center, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China -
Gerontology Center, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China.
Minerva Cardiol Angiol. 2025 Jun;73(3):267-273. doi: 10.23736/S2724-5683.24.06604-3. Epub 2024 Oct 1.
To investigate the protective effect of carvedilol against atherosclerosis by inhibiting the NLRP3 inflammasome.
In-vitro experiments, human umbilical vein endothelial cells (HUVEC) were divided into the control group, ox-LDL group, carvedilol 5 μM group, carvedilol 10 μM group, and carvedilol 20 μM group. The optimal concentration of carvedilol was determined using the CCK-8 method to assess cell proliferation levels and oil red O staining to observe intracellular lipid droplet formation. Subsequently, the cells were further divided into the control group, ox-LDL group, carvedilol 5 μM (optimal concentration) group, and MCC950 (inhibitor of NLRP3 Inflammasome) group. The expression levels of intracellular proteins NLRP3, pro-Caspase-1, Caspase1, pro-IL-1β, IL-1β, p65, GSDMD, and N-GSDMD were detected by ELISA, or Western Blotting.
Compared to the control group, the ox-LDL group exhibited a significant reduction in cell proliferation level (P<0.05), accompanied by an increase in lipid droplet formation upon induction. In contrast, pretreatment with carvedilol at concentrations of 5 μM, 10 μM, and 20 μM effectively promoted cell proliferation (P<0.05) and inhibited intracellular lipid droplet formation. Notably, the most pronounced effect was observed with carvedilol pretreatment at a concentration of 5μM. Furthermore, compared to the control group, HUVEC cells in the ox-LDL group demonstrated substantial upregulation of NLRP3, pro-Caspase-1, Caspase1, pro-IL-1β, IL-1β, p65 GSDMD and N-GSDMD; however, these markers were downregulated following treatment with carvedilol and MCC950 administration-particularly evident in the carvedilol group.
Carvedilol effectively inhibits the progression of atherosclerosis by targeting the NLRP3 inflammasome, thereby providing valuable mechanistic insights into its beneficial effects on atherosclerotic cardiovascular disease.
探讨卡维地洛通过抑制NLRP3炎性小体对动脉粥样硬化的保护作用。
在体外实验中，人脐静脉内皮细胞（HUVEC）分为对照组、氧化型低密度脂蛋白（ox-LDL）组、5 μM卡维地洛组、10 μM卡维地洛组和20 μM卡维地洛组。采用CCK-8法测定细胞增殖水平，用油红O染色观察细胞内脂质滴形成，以确定卡维地洛的最佳浓度。随后，细胞进一步分为对照组、ox-LDL组、5 μM（最佳浓度）卡维地洛组和MCC950（NLRP3炎性小体抑制剂）组。通过酶联免疫吸附测定（ELISA）或蛋白质免疫印迹法（Western Blotting）检测细胞内蛋白质NLRP3、前半胱天冬酶-1（pro-Caspase-1）、半胱天冬酶-1（Caspase1）、前白细胞介素-1β（pro-IL-1β）、白细胞介素-1β（IL-1β）、p65、Gasdermin D（GSDMD）和N端片段化Gasdermin D（N-GSDMD）的表达水平。
与对照组相比，ox-LDL组细胞增殖水平显著降低（P<0.05），诱导后脂质滴形成增加。相反，用5 μM、10 μM和20 μM浓度的卡维地洛预处理可有效促进细胞增殖（P<0.05）并抑制细胞内脂质滴形成。值得注意的是，5 μM浓度的卡维地洛预处理效果最为显著。此外，与对照组相比，ox-LDL组的HUVEC细胞中NLRP3、pro-Caspase-1、Caspase1、pro-IL-1β、IL-1β、p65、GSDMD和N-GSDMD显著上调；然而，用卡维地洛和MCC950处理后，这些标志物下调，在卡维地洛组中尤为明显。
卡维地洛通过靶向NLRP3炎性小体有效抑制动脉粥样硬化的进展，从而为其对动脉粥样硬化性心血管疾病的有益作用提供了有价值的机制见解。
