• BMB Reports
• /
• v.55 no.5
• /
• pp.244-249
• /
• 2022

Characterized by abnormal proliferation and migration of vascular smooth muscle cells (VSMCs), neointima hyperplasia is a hallmark of vascular restenosis after percutaneous vascular interventions. Vaccinia-related kinase 1 (VRK1) is a stress adaption-associated ser/thr protein kinase that can induce the proliferation of various types of cells. However, the role of VRK1 in the proliferation and migration of VSMCs and neointima hyperplasia after vascular injury remains unknown. We observed increased expression of VRK1 in VSMCs subjected to platelet-derived growth factor (PDGF)-BB by western blotting. Silencing VRK1 by shVrk1 reduced the number of Ki-67-positive VSMCs and attenuated the migration of VSMCs. Mechanistically, we found that relative expression levels of β-catenin and effectors of mTOR complex 1 (mTORC1) such as phospho (p)-mammalian target of rapamycin (mTOR), p-S6, and p-4EBP1 were decreased after silencing VRK1. Restoration of β-catenin expression by SKL2001 and re-activation of mTORC1 by Tuberous sclerosis 1 siRNA (siTsc1) both abolished shVrk1-mediated inhibitory effect on VSMC proliferation and migration. siTsc1 also rescued the reduced expression of β-catenin caused by VRK1 inhibition. Furthermore, mTORC1 re-activation failed to recover the attenuated proliferation and migration of VSMC resulting from shVrk1 after silencing β-catenin. We also found that the vascular expression of VRK1 was increased after injury. VRK1 inactivation in vivo inhibited vascular injury-induced neointima hyperplasia in a β-catenin-dependent manner. These results demonstrate that inhibition of VRK1 can suppress the proliferation and migration of VSMC and neointima hyperplasia after vascular injury via mTORC1/β-catenin pathway.

• Natural Product Sciences
• /
• v.26 no.1
• /
• pp.71-78
• /
• 2020

The plant Dendropanax morbifera Léveille is effective folk medicines for the treatment of several conditions, such as infectious diseases, skin diseases, and other illnesses. Although the inhibitory effects of D. morbifera on the proliferation and migration of vascular smooth muscle cells (VSMCs) have been shown in our previous study, its effects in vivo remain to be elucidated. In this study, we aimed to investigate the protective effects of the extracts from D. morbifera (EDM) on neointimal hyperplasia of rat carotid artery and explore the underlying mechanisms. We observed that the ratio of intima to media thickness (I/M) was significantly decreased in the EDM-treated groups by ~80% compared to that of the control. The expression of Ki-67 and proliferating cell nuclear antigen was decreased by ~70% in the EDM-treated groups compared to that of the control. In addition, matrix metalloproteinase (MMP)2 and MMP9 significantly reduced in the neointimal layer of the EDM-treated groups. Moreover, the decreased levels of contractile phenotypic markers of VSMCs, such as α-smooth muscle actin, myocardin, and smooth muscle-myosin heavy chain, were successfully restored by EDM treatment. Furthermore, the levels of synthetic phenotypic markers, cellular retinal binding protein 1 and connexin 43 were also restored to normal levels. These results suggest that EDM inhibits vascular neointimal hyperplasia induced by balloon injury in rats via phenotypic modulation of VSMCs. Therefore, EDM may be a potential drug candidate for the prevention of restenosis.

• Journal of Chest Surgery
• /
• v.41 no.5
• /
• pp.563-567
• /
• 2008

Background: The histomorphological properties of the left anterior desecending artery (LAD), the left internal thoracic arteries (LITA), the radial arteries (RA) and the intercostal arteries (ICA) were studied for their use as a conduit for coronary artery bypass grafting (CABG), and we compared them with each other. Material and Method: All the vessels were harvested from nineteen cadavers (17 males and 2 females). The mid-portion of the LAD, the mid-portion of the LITA, the distal RA and the mid-portion of the 5th ICA were obtained. All of them were stained with hematoxylin-eosin and with Van Gieson's elastin stain. The morphological characteristics were examined and the thicknesses of the intima and media (I/M ratio: the intima to media ratio) were compared using one-way ANOVA tests. Result: The mean age of the cadavers was $61.5{\pm}9.6$ years. The LITA and ICA were elastic arteries, and the LAD and RA were muscular arteries. The I/M ratio showed statistically significant differences: $0.07{\pm}0.03$ in the LITA, $0.16{\pm}0.11$ in the ICA, $0.45{\pm}0.29$ in the RA and $0.93{\pm}0.52$ in the LAD, respectively. Conclusion: This study showed that the degrees of intimal hyperplasia of the CA and the various conduits for CABG were different significantly. The ICA was found to have relatively favorable characteristics as a coronary by pass conduit, but its suitability for clinical use is a challenging issue.