• BMB Reports
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• 제55권5호
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• pp.244-249
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• 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
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• 제26권1호
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• pp.71-78
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• 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
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• 제41권5호
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• pp.563-567
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• 2008

배경: 본 연구에서는 관상동맥 및 이식 가능한 도관들을 조직형태학적으로 비교하여 각 도관의 특성을 알아보고자 하였다. 대상 및 방법: 모든 표본은 해부학 실습용 사체 19구에서 얻었다 채취부위는 좌측 내흉동맥의 중앙부, 5번째 좌측 늑간동맥의 중앙부, 좌전하행지동맥의 중앙부, 좌측 요골동맥의 말단부였다. 표본은 Hematoxylin-Eosin (H&E) 염색과 Van Gieson's elastin 염색을 하여 광학현미경으로 관찰하였고, 동맥 각 층의 두께는 $Metamorpho^{(R)}$를 이용하여 측정하였으며, 동맥별로 내막(I)과 중간막(M)의 비율(I/M ratio)을 비교하였다. 통계는 SPSS 12.0을 사용하였으며, 각 동맥간의 통계적 유의성은 일원배치 분산분석을 이용하였다. 결과: 남자가 17예, 여자는 2예였으며, 평균 나이는 $61.5{\pm}9.6$세였다. 내흉동맥과 늑간동맥은 탄력형 동맥의 소견을 보였으며, 좌전하행지동맥과 요골동맥은 근육형 동맥의 소견을 보였다. 내막과 중간막의 비는 내흉동맥 $0.07{\pm}0.03$, 늑간동맥 $0.16{\pm}0.11$, 요골동맥 $0.45{\pm}0.29$, 좌전하행지동맥 $0.93{\pm}0.52$ 순으로 관찰되었다. 각 동맥간 내막증식 정도는 F=30.67, p=0.00으로 통계적 유의성이 있었다. 결론: 내흉동맥, 늑간동맥, 요골동맥, 좌전하행지동맥 순으로 내피의 과증식이 적었고, 근육형 동맥보다 탄력형 동맥에서 내피의 과증식이 적은 것을 확인할 수 있었다. 내흉동맥과 조직학적으로 유사한 늑간동맥을 이식 도관으로 사용할 수 있을 것으로 생각되며, 늑간동맥의 사용 방법에 대해서는 좀 더 연구가 필요하겠다.