Dickkopf‑1/cysteine‑rich angiogenic inducer 61 axis mediates palmitic acid‑induced inflammation and apoptosis of vascular endothelial cells

• Published in: Molecular medicine reports Vol. 23; no. 2
• Main Authors: Gan, Yi-Rong, Wei, Ling, Wang, Yan-Zhen, Kou, Zong-Ke, Liang, Tian-Xiang, Ding, Guan-Waner, Ding, Yan-Hong, Xie, Ding-Xiong
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications 01.02.2021; Spandidos Publications UK Ltd; D.A. Spandidos
• Subjects: Angiogenesis; Antibodies; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Arteriosclerosis; Atherosclerosis; Biotechnology; Cardiovascular disease; Cardiovascular diseases; Cysteine; Cysteine-Rich Protein 61 - genetics; Cysteine-Rich Protein 61 - metabolism; Cytokines; Development and progression; Dkk1 protein; Endothelial cells; Experiments; Gene expression; Genetic aspects; Health aspects; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Inflammation - chemically induced; Inflammation - genetics; Inflammation - metabolism; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Mortality; mRNA; Nitric oxide; Palmitic acid; Palmitic Acid - adverse effects; Palmitic Acid - pharmacology; Physiological aspects; Plasmids; Protein expression; Proteins; Signal transduction; Signal Transduction - drug effects; Signal Transduction - genetics; Software; Vascular endothelium; Wnt protein; Wnt proteins; β-Catenin; China
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2020.11761

Cardiovascular diseases (CVDs) are a major cause of mortality around the world, and the presence of atherosclerosis is the most common characteristic in patients with CVDs. Cysteine‑rich angiogenic inducer 61 (CCN1) has been reported to serve an important role in the pathogenesis of atherosclerotic lesions. The aim of the present study was to investigate whether CCN1 could regulate the inflammation and apoptosis of endothelial cells induced by palmitic acid (PA). Dickkopf‑1 (DKK1) is an important antagonist of the Wnt signaling pathway, which can specifically inhibit the classic Wnt signaling pathway. Firstly, the mRNA and protein expression levels of CCN1 were detected. Additionally, endothelial nitric oxide (NO) synthase (eNOS), DKK1, β‑catenin, and inflammation‑ and apoptosis‑associated proteins were measured. Detection of NO was performed using a commercial kit. The expression levels of inflammatory cytokines were assessed to explore the effect of CCN1 on PA‑induced inflammation. TUNEL assay was used to detect the apoptosis of endothelial cells. The results revealed that PA upregulated the expression levels of CCN1, inflammatory cytokines and pro‑apoptotic proteins in endothelial cells. PA decreased the production of NO, and the levels of phosphorylated‑eNOS, whereas knockdown of CCN1 partially abrogated these effects triggered by PA. Furthermore, the Wnt/β‑catenin signaling pathway was activated in PA‑induced endothelial cells; however, the levels of DKK1 were downregulated. Overexpression of DKK1 could reduce CCN1 expression via inactivation of the Wnt/β‑catenin signaling pathway. In conclusion, knockdown of CCN1 attenuated PA‑induced inflammation and apoptosis of endothelial cells via inactivating the Wnt/β‑catenin signaling pathway.