This study aimed to examine the effect of a mild elevation in serum cholesterol level in a porcine coronary overstretch restenosis model using a balloon angioplasty catheter or drug-eluting coronary stent. Pigs were divided into two groups and were fed a commercial normal diet (CND, n = 4) or a high-fat diet (HFD, n = 4) for 5 weeks. Coronary overstretch injury by balloon angioplasty or stent implantation was induced in the left anterior descending and left circumflex artery after 1 week of feeding. Histopathological analysis was performed at 4 weeks after coronary injury. During the experiment, the total cholesterol level in the HFD group increased by approximately 44.9% (from 65.9 ± 3.21 mg/dL at baseline to 95.5 ± 9.94 mg/dL at 5 weeks). The lumen area in the CND group was reduced in comparison with that in the HFD group after balloon angioplasty. After stent implantation, the injury score showed no significant difference. There were significant differences in the neointimal area (2.7 ± 0.33 mm2 in the CND group vs. 3.3 ± 0.34 mm2 in the HFD group, p<0.05), lumen area (2.6 ± 0.54 mm2 in the CND group vs. 2.0 ± 0.33 mm2 in the HFD group, p<0.05), and percent area stenosis (52.0 ± 7.96% in the CND group vs. 62.4 ± 5.15% in the HFD group, p<0.05). Body weight change was not different between the two groups. Increased serum cholesterol level activated vascular smooth muscle cell proliferation in the porcine coronary overstretch model.
목적 : 증식당뇨망막병증과 같은 망막질환은 시력상실에 이르게 하는 현대 눈 질환 중 가장 중요한 질환이다. 본 논문에서는 산화스트레스와 관련된 망막변성과 같은 혈관리모델링을 유발하는 혈관평활근세포(vascular smooth muscle cell, VSMC)의 활성화에 대한 4-hydroxynonenal(HNE)의 중요성에 대해 고찰하고자 한다.
방법 : 망막질환은 비정상적 혈관신생의 특징이 있으며 이는 세포증식과 세포자살의 증가와 관련되어 있다. 증식당뇨망막병증에 있어 혈관신생은 기존에 존재하고 있는 혈관으로부터 새로운 모세혈관들이 자라나는 복잡한 단계의 현상이다. 따라서 우리는 이와 같은 혈관리모델링을 유발하는데 있어 HNE의 VSMC의 활성화에 대한 역할을 조사하였다.
결과 : HNE는 VSMC에서 nitro oxide(NO)의 생성을 증가시켰다. HNE는 세포구조의 교란과 다양한 산화스 트레스 관련 퇴행과정을 일으킴으로써 혈관기능이상에 이르게 한다. 또한 HNE는 protein kanse B(Akt)의 인산화를 증가시켰다. HNE에 의한 산화스트레스는 Akt 인산화와 세포증식의 유발에 있어 중재자의 역할을 하는 것으로 사료된다.
결론 : HNE에 의한 산화스트레스는 망막동맥경화의 발병과 혈관신생과 같은 혈관의 교란에 중요한 역할을 하는 것으로 사료된다. HNE의 VSMC 활성화에 대한 역할은 산화스트레스 관련 망막변성에 있어 혈관리모델링의 촉진과 발달에 중요한 역할을 하는 것으로 사료된다.
Periodontal diseases have been associated with the development of cardiovascular diseases. Accumulating evidences have indicated that Porphyromonas gingivalis , a major periodontopathic pathogen, plays a critical role in the pathogenesis of atherosclerosis. In the present study, we demonstrated that P. gingivalis lipopolysaccharide (LPS) increases the mRNA and protein expression of matrix metalloproteinase-9 (MMP-9) in rat vascular smooth muscle cells. We showed that the MMP-9 expression induced by P. gingivalis LPS is mediated by the activation of signal transducer and activator of transcription 3 (STAT3) in vascular smooth muscle cells. Furthermore, the inhibition of STAT3 activity reduced P. gingivalis LPS-induced migration of vascular smooth muscle cells. Overall, our findings indicate that P. gingivalis LPS stimulates the migration of vascular smooth muscle cells via STAT3-mediated MMP-9 expression.
목적 : 본 연구는 완곡추적 안구운동과 경부신전근 진동자극법의 결합중재가 만성 뇌졸중 환자의 편측무시와 일상생활활동 수행에 미치는 영향을 확인하는 것이다.
연구방법 : 본 연구는 발병 후 6개월 이상 지난 3명의 뇌졸중 편측무시 환자를 대상으로 하였으며, 단일대상연구 방법 중 ABAC디자인으로 연구를 진행하였다. 연구는 기초선(A1) 1주, 중재기(B) 2주, 기초선(A2) 1주, 그리고 중재기(C) 2주로 총 6주간 진행되었으며, 중재기(B)에서는 완곡추적 안구운동(Smooth Pursuit Eye Movement; SPEM)의 단일중재를, 중재기(C)에서는 경부신전근 진동자극법(Neck Muscle Vibration; NMV)과 SPEM의 결합중재를 실시하였다. 평가는 매회기 선 나누기 검사와 벨 테스트(Bells test)를 실시하였으며, 한국판 캐서린 버지고 척도(Korean-Catherine Bergego Scale; K-CBS)와 한국판 일상생활활동 중심 작업기반 신경행동 평가(Korean version of ADL-focused Occupation-based Neurobehavioral Evaluation; K-A-ONE)를 기초선(A1)의 첫 회기와 각 중재기의 마지막 회기에 시행하였다.
결과 : 연구결과 SPEM과 NMV를 단일 또는 결합하여 적용하였을 때 편측무시의 지필검사(선 나누기 검사와 벨 테스트)와 관찰적 검사(K-CBS와 K-A-ONE)에서 편측무시가 개선됨을 확인하였고, 특히 결합중재시에 더 효과가 좋았던 것으로 나타났다. 그리고 편측무시가 개선됨에 따라 일상생활활동의 수행(K-A-ONE)에서도 향상을 보였는데, 편측무시 환자의 일상생활을 저해하는 신경행동 손상은 편측무시 뿐만 아니라 공간관계나 마비와 같은 손상 등이 영향을 미치는 것으로 나타나 다양한 신경행동 손상의 중재를 포함하는 포괄적인 재활프로그램을 계획해야함을 확인하였다.
결론 : 본 연구를 통해 SPEM과 NMV의 결합중재가 만성 뇌졸중 환자의 편측무시를 감소시키고 일상생활 활동 수행을 향상시키는데 효과적인 중재라는 것을 확인하였다.
Porphyromonas gingivalis, a foremost periodontal pathogen, has been known to cause periodontal diseases. Epidemiologic evidences have indicated the involvement of P. gingivalis in the development of cardiovascular diseases. In this study, we show that the P. gingivalis lipopolysaccharide increases the mRNA expression and protein secretion of interleukin-6 in vascular smooth muscle cells. We demonstrate that P. gingivalis LPS activates the extracellular signalregulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and Akt, which mediate the IL-6 expression in vascular smooth muscle cells. Also, P. gingivalis LPS stimulates the vascular smooth muscle cell migration, which is a critical step for the progression of atherosclerosis. Moreover, neutralization of the IL-6 function inhibits the migration of vascular smooth muscle cells induced by P. gingivalis LPS. Taken together, these results indicate that P. gingivalis LPS promotes the expression of IL-6, which in turn increases the migration of vascular smooth muscle cells.
Platelet derived growth factor (PDGF)-BB is one of the most potent vascular smooth muscle cell (VSMC) proliferative factors, and abnormal VSMC proliferation by PDGF-BB plays an important role in the development and progression of atherosclerosis. The aim of this study was to assess the effect of YP 12, a newly synthesized obovatol derivative, on the proliferation of PDGF-BB-stimulated rat aortic VSMCs. The anti-proliferative effects of YP 12 on rat aortic VSMCs were examined by direct cell counting and by using [3H] thymidine incorporation assays. It was found that YP 12 potently inhibited the growth of VSMCs. The pre-incubation of YP 12 (1-4 μM)significantly inhibited the proliferation and DNA synthesis of 25 ng/ml PDGF-BB-stimulated rat aortic VSMCs in a concentration-dependent manner. In accordance with these findings, YP 12 revealed blocking of the PDGF-BB-inducible progression through G0/G1 to S phase of the cell cycle in synchronized cells. Whereas, YP 12 did not show any cytotoxicity in rat aortic VSMCs in this experimental condition by WST-1 assay. These results also show that YP 12may have potential as an anti-proliferative agent for the treatment of restenosis and atherosclerosis.
Atherosclerosis, a disease of the large arteries, is the primary cause of heart disease and stroke. The abnormal proliferation of vascular smooth muscle cells (VSMCs) in arterial walls is an important pathogenetic factor of vascular disorders like atherosclerosis and restenosis after angioplasty. In the current study, the possible anti-proliferative effect of vitexin originated from Acer palmatum was investigated in rat aortic VSMCs. Vitexin was found to potently inhibit 5% fetal bovine serum (FBS)-induced growth of VSMCs. Pre-treatment with vitexin (5-50 μg/ml) in VSMCs for 24 h resulted in a significant decrease in cell number, i.e., the inhibition rates were 5.4±7.1, 52.5±8.4, and 78.9±5.2% with vitexin treatments of 5, 20, and 50 μg/ml, respectively. In addition, trteatment with vitexin resulted in significant and dose-dependent inhibition of 5% FBS-induced DNA synthesis. Vitexin did not show any cytotoxicity in rat aortic VSMCs under this experimental condition. These results indicate the potential for development of vitexin as an anti-proliferative agent for treatment of angioplasty restenosis and atherosclerosis.
Periodontal disease, a form of chronic inflammatory bacterial infectious disease, is known to be a risk factor for cardiovascular disease (CVD). Porphyromonas gingivalis has been implicated in periodontal disease and widely studied for its role in the pathogenesis of CVD. A previous study demonstrating that periodontopathic P. gingivalis is involved in CVD showed that invasion of endothelial cells by the bacterium is accompanied by an increase in cytokine production, which may result in vascular atherosclerotic changes. The present study was performed in order to further elucidate the role of P. gingivalis in the process of atherosclerosis and CVD. For this purpose, invasion of human aortic smooth muscle cells (HASMC) by P. gingivalis 381 and its isogenic mutants of KDP150 (fimA⁻), CW120 (ppk⁻) and KS7 (relA⁻) was assessed using a metronidazole protection assay. Wild type P. gingivalis invaded HASMCs with an efficiency of 0.12%. In contrast, KDP150 failed to demonstrate any invasive ability. CW120 and KS7 showed relatively higher invasion efficiencies, but results for these variants were still negligible when compared to the wild type invasiveness. These results suggest that fimbriae are required for invasion and that energy metabolism in association with regulatory genes involved in stress and stringent response may also be important for this process. ELISA assays revealed that the invasive P. gingivalis 381 increased production of the proinflammatory cytokine interleukin (IL)-1β and the chemotactic cytokines (chemokine) IL (interleukin)-8 and monocyte chemotactic (MCP) protein-1 during the 30-90 min incubation periods (P<0.05). Expression of RANTES (regulation upon activation, normal T cell expressed and secreted) and Toll-like receptor (TLR)-4, a pattern recognition receptor (PRR), was increased in HASMCs infected with P. gingivalis 381 by RT-PCR analysis. P. gingivalis infection did not alter interferon--inducible protein-10 expression in HASMCs. HASMC nonspecific necrosis and apoptotic cell death were measured by lactate dehydrogenase (LDH) and caspase activity assays, respectively. LDH release from HASMCs and HAMC caspase activity were significantly higher after a 90 min incubation with P. gingivalis 381. Taken together, P. gingivalis invasion of HASMCs induces inflammatory cytokine production, apoptotic cell death, and expression of TLR-4, a PRR which may react with the bacterial molecules and induce the expression of the chemokines IL-8, MCP-1 and RANTES. Overall, these results suggest that invasive P. gingivalis may participate in the pathogenesis of atherosclerosis, leading to CVD.
It is study was designed to characterize endotoxin-induced prostaglandin production in primary cultured rat vascular smooth muscle cells (VSMC). The time course for prostag)andim synthesis in lipopolysaccharide (LPS)-stimulated VSMC showed that the maximum production was reached in 12 hours. LPS induced prostaglandin H2 synthase (PGHS) activity in VSMC and the time course profile in the changes of PGHS activity paralleled that of total prostaglandin production. Differential treatment showed that 4 hours' exposure to LPS was enough for the maximum effect on the prostaglandin production and this effect was completely inhibited by the co-treatment of actinomycin D, a transcription inhibitor. These results suggest that LPS effect might be determined within 4 hours. Actinomycin D increased PGHS activity without affecting prostaglandin production if added 4 hours after LPS treatment. On the other hand, cycloheximide, a translation inhibitor, augmented LPS-induced prostaglandin production if treated during first four hours, but it inhibited LPS-induced PGHS activity regardless of treatment schedule. These results suggeat the existence of multiple regulating mechanisms in the LPS-induced prostaglandin synthesis.
The objective of this study is to investigate the direct effects of green tea catechins(GTC) on vascular smooth muscle tension and ^(46)Ca^(2+) uptake in rat aorta. The methods used in this study are isometric tension measurements using physiograph, Lanthanum method for ^(46)Cac^(2+) (2 uCi/ml) uptake measurement in rat aorta. GTC modified tension induced by 40 mM KCl or 1 uM norepinephrine in rat aorta. Low concentrations of GTC($lt;0.5 mg/m increased tension by 40 mM KCl or 1 tM norepinephrine, individually. However, high concentrations of GTC($gt; 0.5 mg/ml) inhibited tension by 40 mM KCl or 1 uM norepinephrine, individually. GTC increased ^(45)Ca uptake induced by 40 mM KCl in a dose-dependent manner. From these results, GTC has the dual actions in vascular smooth muscle in vitro. Low concentrations of GTC augments tension by K or norepinephrine. However, high concentrations of GTC inhibits tension by K or norpeinephrine. GTC may have Ca^(2+) channel activation action, which may result in unphysiological vasodilation by Ca^(2+) overload in vascular smooth muscle.
Cynanchum wilfordii Radix (CWR), Arctium lappa L (ALL), and Dioscorea opposite (DO) have been known to improve blood lipid profile, blood pressure, and inflammation. To find the optimal combination ratio of CWR, ALL, and DO in terms of vascular health improvement, we compared the effects of various combinations on gene expression of Vascular cell adhesion protein 1 (VCAM-1) in human aortic smooth muscle cells (HASMC). VCAM-1 mediates endothelial leukocyte adhesion and is upregulated in atherosclerosis. Cells was stimulated by TNF-α (10 ng/㎖, 2h) and treated with various combinations for 24 h. A combination (CADM5, CWR:ALL:DO = 2:1:1) showed the strongest suppression of VCAM-1 so that CADM5 was chosen for further experiments. We performed cell viability test with CADM5 (0, 3.125, 12.5, 25, 50, and 100 ㎍/㎖) and no cytotoxicity was found. We also investigated the effect of CADM5 on protein expression of VCAM-1, ICAM-1, Nrf-2, and HO-1 using western blotting. We found that CADM5 diminished the expression of VCAM-1 and increased the expression of Nrf-2 and HO-1. Therefore, we concluded that CADM5 (CWR:ALL:DO = 2:1:1) effectively improves vascular health by regulating the expression of VCAM-1.