Abstract
Objectives To observe the effect of avβ3 single-stranded (ss) DNA on proliferation and migration of vascular smooth muscle cells (VSMCs) and its potential mechanism. Background Percutaneous transluminal coronary angioplasty (PTCA) is currently the preferred method for the treatment of coronary heart disease. However, vascular restenosis still occurs after PTCA treatment, severely affecting the clinical efficacy of PTCA. Integrin avβ3, which is widely expressed on various cell surfaces, plays an important role in the proliferation and migration of VSMCs. Methods In this experiment, we used systematic evolution of ligands by exponential enrichment (SELEX) to screen out avβ3 ssDNA, which has high affinity and specificity to the avβ3 protein. MTT, Transwell, and cell scratch assays were carried out to examine the effect of avβ3 ssDNA on the proliferation and migration of VSMCs. Flow cytometry was performed to detect apoptosis and cell cycle progression. The effect of avβ3 ssDNA on the Ras-phosphatidylinositol-4,5-bisphosphate 3-kinase/mitogen-activated protein kinase (PI3K/MAPK) signaling pathway was evaluated by quantitative reverse transcription polymerase chain reaction and western blot. Results In the present study, we found that avβ3 ssDNA significantly decreased the expression of osteopontin, focal adhesion kinase, Ras, p-PI3K, and p-MAPK at both mRNA and protein levels (P < 0.05). Avβ3 ssDNA also inhibited VSMC proliferation and migration while promoting apoptosis (P < 0.05), as demonstrated by the upregulation of the proapoptotic proteins Bax and active caspase 3 (P < 0.05). Conclusions The findings suggest that avβ3 ssDNA inhibited the proliferation and migration of VSMCs by suppressing the activation of Ras-PI3K/MAPK signaling.
Highlights
Coronary heart disease is a high-risk condition among cardiovascular diseases and has one of the highest mortality rates worldwide
Percutaneous transluminal coronary angioplasty (PTCA) is one of the main methods for the clinical treatment of coronary heart disease, but vascular restenosis still occurs after treatment, severely limiting the e cacy of PTCA in clinical practice. e proliferation and migration of vascular smooth muscle cells (VSMCs) has been considered the major cause of post-PTCA restenosis [2, 3]. erefore, the development of ways to inhibit VSMC migration and proliferation has become an urgent problem in cardiovascular research
We further investigated the expression of OPN and FAK, which are related to VSMC proliferation and migration. e relative protein (Figure 4(c)) and mRNA (Figure 4(d)) expression of OPN and p-FAK/FAK in VSMCs treated with platelet-derived growth factor (PDGF) and avβ3 ssDNA were significantly lower than those in VSMC treated with PDGF only (P < 0.05)
Summary
Coronary heart disease is a high-risk condition among cardiovascular diseases and has one of the highest mortality rates worldwide. E proliferation and migration of vascular smooth muscle cells (VSMCs) has been considered the major cause of post-PTCA restenosis [2, 3]. It is closely related to embryonic development, angiogenesis, Cardiovascular erapeutics invasion and metastasis of tumor cells, and inflammation [4, 5]. Avβ is highly expressed in osteoclasts and is the most important integrin regulating osteoclast function, participating in osteoclast differentiation, migration, adhesion, and formation of closed regions [6]. Avβ is hardly expressed in mature vascular endothelial cells but is highly expressed in activated vascular endothelial cells. It mediates the proliferation, migration, and adhesion of vascular endothelial cells, transmits survival signals into cells, and inhibits apoptosis [7]
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