Phoenixin-14 alleviates inflammatory smooth muscle cell-induced endothelial cell dysfunction in vitro

Cong Ling; Yang Yang; Xiling Hu; Meiqin Cai; Hui Wang; Chuan Chen

doi:10.1016/j.cyto.2022.155973

Phoenixin-14 alleviates inflammatory smooth muscle cell-induced endothelial cell dysfunction in vitro

Cytokine. 2022 Sep:157:155973. doi: 10.1016/j.cyto.2022.155973. Epub 2022 Jul 27.

Authors

Cong Ling¹, Yang Yang², Xiling Hu³, Meiqin Cai¹, Hui Wang⁴, Chuan Chen⁵

Affiliations

¹ Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
² Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
³ Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
⁴ Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China. Electronic address: doctorwanghui@126.com.
⁵ Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China. Electronic address: chenchuangd@hotmail.com.

PMID: 35907364
DOI: 10.1016/j.cyto.2022.155973

Abstract

Background: Intracranial aneurysm (IA) is cerebrovascular disorder which refers to local vessel wall damage to intracranial arteries, forming abnormal bulge. Both endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are closely associated with IA formation and rupture. Inflammatory SMCs (iSMCs) were reported to induce EC dysfunction and result in IA progression. Phoenixin-14 (PNX-14) is a recently discovered brain peptide with pleiotropic roles, which participates in reproduction, cardio protection, lipid deposition and blood glucose metabolism. PNX-14 was previously reported to protect brain endothelial cells against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cell injury. Therefore, our study was designed to investigate the influence of PNX-14 on iSMCs-induced endothelial dysfunction.

Methods: Inflammation in SMCs was induced by cyclic mechanical stretch. Human umbilical vein endothelial cells (HUVECs) were exposed to SMC- or iSMC-conditioned medium and then treated with 100 nM PNX-14 for 24 h. The levels of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) in cell supernatants were analyzed by ELISA. Cell viability, apoptosis, angiogenesis and migration were subjected to CCK-8 assay, flow cytometry analysis, tube formation assay and Transwell migration assay. The protein levels of proinflammatory cytokines and apoptosis markers (Bcl-2 and Bax) were evaluated by western blotting.

Results: Cyclic mechanical stretch upregulated IL-1β, IL-6 and TNF-α levels in SMCs. Treatment with SMC- or iSMC-conditioned medium HUVECs inhibited cell viability, angiogenesis and migration and induced apoptosis in HUVECs. iSMC-conditioned medium has more significant effects on cell functions. However, the influence of SMC- or iSMC-conditioned medium treatment on HUVEC biological functions were reversed by PNX-14 treatment. PNX-14 exerts no significant influence on the biological functions of HUVECs treated with SMC medium.

Conclusion: PNX-14 alleviates iSMCs-induced endothelial cell dysfunction in vitro.

Keywords: Endothelial dysfunction; Inflammation; Intracranial aneurysm; Phoenixin-14; Smooth muscle cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Culture Media, Conditioned / metabolism
Culture Media, Conditioned / pharmacology
Cytokines / metabolism
Human Umbilical Vein Endothelial Cells
Humans
Interleukin-6 / metabolism
Intracranial Aneurysm*
Myocytes, Smooth Muscle / metabolism
Peptides
Tumor Necrosis Factor-alpha* / metabolism

Substances

Culture Media, Conditioned
Cytokines
Interleukin-6
Peptides
Tumor Necrosis Factor-alpha