AUTHOR=Liu Xing , Huang Zhuoshan , Zhang Yuanyuan , Shui Xing , Liu Fanmao , Wu Zhen , Xu Shiyue 

TITLE=Lacidipine Ameliorates the Endothelial Senescence and Inflammatory Injury Through CXCR7/P38/C/EBP-β Signaling Pathway

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 8 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.692540

DOI=10.3389/fcvm.2021.692540

ISSN=2297-055X

ABSTRACT=Background: Lacidipine, a third-generation calcium channel blocker, exerts beneficial effects on the endothelium of hypertensive patients in addition to blood pressure lowering. However, the detailed mechanism underlying Lacidipine-related endothelial protection is still elusive.
Methods: Sixteen spontaneous hypertensive rats (SHRs) were randomly divided into two groups: Lacidipine-treated SHR group and saline-treated control group. Tail systolic blood pressure was monitored for four consecutive weeks. Endothelial Cells (ECs) were pretreated with Lacidipine prior to being stimulated with H2O2, Bleomycin or LPS in vitro. Then, Cell activity, migration and senescence was measured by Cell Counting Kit-8 assay, transwell assay and β-galactosidase staining, respectively. The fluorescent probe DCFH-DA was used to assess the intracellular reactive oxidative species (ROS). Related protein expression was detected by western blotting and immunofluorescence.
Results: Our data showed that Lacidipine treatment lowered the blood pressure of SHR rats accompanied by the elevation of CXCR7 expression and suppression of P38 and C/EBP-β compared with control group. In vitro experiments further demonstrated that Lacidipine increased the cell viability and function of ECs under oxidative stress, cell senescence and inflammatory activation via CXCR7/P38/ signaling pathway.
Conclusions: Our results suggested that Lacidipine plays a protective role in endothelial cell senescence, oxidative and inflammatory injury through the regulation of CXCR7/P38/ C/EBP-β signaling pathway.