沙库巴曲缬沙坦通过 Notch 信号通路和 ERK1/2 通路抑制血管平滑肌细胞增殖。

Sacubitril/valsartan inhibits the proliferation of vascular smooth muscle cells through notch signaling and ERK1/2 pathway.

机构信息

Department of Cardiology, The Affiliated Hospital of Qingdao University, Road No. 59 Haier, Qingdao, 266000, China.

出版信息

BMC Cardiovasc Disord. 2024 Feb 14;24(1):106. doi: 10.1186/s12872-024-03764-8.

DOI:10.1186/s12872-024-03764-8

PMID:38355423

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10865611/

Abstract

AIMS

To explore the role and mechanism of Notch signaling and ERK1/2 pathway in the inhibitory effect of sacubitril/valsartan on the proliferation of vascular smooth muscle cells (VSMCs).

MAIN METHODS

Human aortic vascular smooth muscle cells (HA-VSMCs) were cultured in vitro. The proliferating VSMCs were divided into three groups as control group, Ang II group and Ang II + sacubitril/valsartan group. Cell proliferation and migration were detected by CCK8 and scratch test respectively. The mRNA and protein expression of PCNA, MMP-9, Notch1 and Jagged-1 were detected by qRT-PCR and Western blot respectively. The p-ERK1/2 expression was detected by Western blot.

KEY FINDINGS

Compared with the control group, proliferation and migration of VSMCs and the expression of PCNA, MMP-9, Notch1, Jagged-1 and p-ERK1/2 was increased in Ang II group. Sacubitril/valsartan significantly reduced the proliferation and migration. Additionally, pretreatment with sacubitril/valsartan reduced the PCNA, MMP-9, Notch1, Jagged-1 and p-ERK1/2 expression.

摘要

目的

探讨 Notch 信号通路和 ERK1/2 通路在沙库巴曲缬沙坦抑制血管平滑肌细胞（VSMCs）增殖中的作用及机制。

主要方法

体外培养人主动脉血管平滑肌细胞（HA-VSMCs）。将增殖的 VSMCs 分为对照组、Ang II 组和 Ang II+沙库巴曲缬沙坦组。分别采用 CCK8 法和划痕实验检测细胞增殖和迁移情况。采用 qRT-PCR 和 Western blot 检测 PCNA、MMP-9、Notch1 和 Jagged-1 的 mRNA 和蛋白表达。采用 Western blot 检测 p-ERK1/2 的表达。

主要发现

与对照组相比，Ang II 组 VSMCs 的增殖和迁移能力增加，PCNA、MMP-9、Notch1、Jagged-1 和 p-ERK1/2 的表达增加。沙库巴曲缬沙坦可显著降低 VSMCs 的增殖和迁移能力。此外，沙库巴曲缬沙坦预处理可降低 PCNA、MMP-9、Notch1、Jagged-1 和 p-ERK1/2 的表达。