Substance P ameliorates TNF‐α‐mediated impairment of human aortic vascular cells in vitro

• Published in: Clinical and experimental pharmacology & physiology 2021-09, Vol.48 (9), p.1288-1297
• Main Authors: Kim, Do Young, Piao, Jiyuan, Park, Jeong Seop, Lee, Dahyeon, Hong, Hyun Sook
• Format: Article
• Language: English
• Subjects: AKT protein; Aorta; Aorta - cytology; Aorta - drug effects; Aorta - metabolism; Aorta - pathology; aortic endothelial cell; aortic smooth muscle cells; Bioavailability; Cardiovascular diseases; Cell adhesion; Cell Adhesion - drug effects; Cell injury; Cells, Cultured; Chemokine CCL2 - metabolism; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelium; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Extracellular matrix; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Humans; Immune system; Impairment; Inflammation; Injury prevention; Metabolism; Monocyte chemoattractant protein; Monocytes; Muscles; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Nitric oxide; Nitric Oxide - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Smooth muscle; Substance P; Substance P - metabolism; Substance P - pharmacology; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumors; Vascular diseases
• ISSN: 0305-1870; 1440-1681; 1440-1681
• DOI: 10.1111/1440-1681.13533

Vascular diseases are caused by endothelial dysfunction due to inflammation. On endothelial injury, the expression of extracellular matrix (ECM) is enhanced and nitric oxide (NO) bioavailability becomes deficient. This condition affects endothelial metabolism and leads to vascular destruction. The aim of this investigation was to determine whether substance P (SP) is able to protect the endothelium against inflammatory stress. To this end, aortic endothelial cells were pre‐treated with SP, followed by tumour necrosis factor α (TNF‐α), and cellular responses were evaluated using a combination of cell biology and quantification assays, as well as western blot analyses. Our results show that TNF‐α enhanced ECM expression and reduced NO production within 4 hours, promoting immune cell adhesion to the endothelium and monocyte chemoattractant protein‐1 (MCP‐1) secretion from aortic smooth muscle cells. However, SP treatment ameliorated TNF‐α‐induced endothelial impairment by maintaining low ECM levels. Our data suggest that this protective effect is mediated by Akt activation and NO‐enriched conditions. The inhibition of aortic endothelial cell injury by SP also reduced MCP‐1 production in aortic smooth muscle cells. Together, our data indicate that SP can protect aortic endothelial and smooth muscle cells from inflammatory injury, which suggests that SP may prevent cardiovascular disease.