Abstract
Background Melatonin has been demonstrated to protect against calcification in cyclosporine nephrotoxicity. The wingless-type MMTV integration site family member 1 (Wnt1)/β-catenin pathway is associated with cardiovascular calcification. This study aimed to explore whether melatonin could attenuate VSMC calcification through regulating the Wnt1/β-catenin signaling pathway. Methods The effects of melatonin on vascular calcification were investigated in vascular smooth muscle cells (VSMCs). Calcium deposits were visualized by Alizarin Red Staining. Calcium content and alkaline phosphatase (ALP) activity were used to evaluate osteogenic differentiation. Western blots were used to measure the expression of runt-related transcription factor 2 (Runx2), α-smooth muscle actin (α-SMA), and cleaved caspase-3. Results Melatonin markedly ameliorated calcium deposition and ALP activity. Runx2 and cleaved caspase-3 were found to be reduced and α-SMA was found to be increased by melatonin, together with a decrease in apoptosis. Immunofluorescence assay revealed a lower Runx2 protein level in the melatonin group. Melatonin treatment significantly decreased the expression of Wnt1 and β-catenin. Treatment with lithium chloride or transglutaminase 2 abrogated the protective effects of melatonin. Conclusion Melatonin can attenuate β-GP-induced VSMC calcification through the suppression of Wnt1/β-catenin system.
Highlights
Vascular calcification (VC) is prevalent in coronary artery disease, and the extent of VC predicts cardiovascular risk [1].e causes of calcification in atherosclerosis include dysregulated matrix metabolism, epitaxial mineral deposition, inflammation, oxidative stress, and apoptosis [2]
VC mainly occurs in vascular smooth muscle cells (VSMCs) [3]. e wingless-type MMTV integration site family member 1 (Wnt1) protein plays important roles in the proliferation, differentiation, and death in many cells, and the Wnt1/ β-catenin pathway is associated with cardiovascular calcification [4]
Luzindole abrogated the protective effects of melatonin on VSMC calcification (P < 0.05). e mRNA expression of α-smooth muscle actin (α-SMA) was reduced in β-GP group as compared to the control group. e β-GPinduced reduction was mitigated by melatonin, but this effect was blocked by luzindole treatment
Summary
Vascular calcification (VC) is prevalent in coronary artery disease, and the extent of VC predicts cardiovascular risk [1].e causes of calcification in atherosclerosis include dysregulated matrix metabolism, epitaxial mineral deposition, inflammation, oxidative stress, and apoptosis [2]. E wingless-type MMTV integration site family member 1 (Wnt1) protein plays important roles in the proliferation, differentiation, and death in many cells, and the Wnt1/ β-catenin pathway is associated with cardiovascular calcification [4]. Several studies have shown that melatonin protects against VSMC inflammation and apoptosis [6, 7]. E aim of our study was to examine whether melatonin could attenuate VSMC calcification through regulating the Wnt1/β-catenin signaling pathway. E wingless-type MMTV integration site family member 1 (Wnt1)/β-catenin pathway is associated with cardiovascular calcification. Is study aimed to explore whether melatonin could attenuate VSMC calcification through regulating the Wnt1/β-catenin signaling pathway. E effects of melatonin on vascular calcification were investigated in vascular smooth muscle cells (VSMCs). Melatonin can attenuate β-GP-induced VSMC calcification through the suppression of Wnt1/β-catenin system
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