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.

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.