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Balloon Injury (balloon + injury)
Selected AbstractsAqueous extract of rhubarb stabilizes vulnerable atherosclerotic plaques due to depression of inflammation and lipid accumulationPHYTOTHERAPY RESEARCH, Issue 7 2008Yunfang Liu Abstract The study evaluated the effect of the traditional Chinese medicine rhubarb on the stability of atherosclerotic plaque. Atherosclerotic lesions were induced in rabbits through balloon injury with a high-cholesterol diet and then were divided into a control group, a rhubarb group and a simvastatin group. At week 24 recombinant-p53 adenoviruses were locally delivered to the atherosclerotic plaques. At week 26 plaque rupture was triggered by the intra-arterial Chinese Russell's viper venom and histamine. Serological, ultrasonographic, pathologic, immunohistochemical and gene expression studies were performed. The results showed that the incidence of plaque rupture in the rhubarb group and the simvastatin group was significantly lower than that in the control group (42.86% and 35.71% versus 80.00%, both p < 0.05). Serum TC, LDL-C (p < 0.05,0.01), IMT (both p < 0.01), PA (both p < 0.01), PB (%) (both p < 0.01) and the mRNA and protein expressions of TLR2, TLR4 and NF- ,B (p < 0.05, 0.01, respectively) in the rhubarb group and the simvastatin group were significantly lower than those in the control group. In contrast, AIIc% (both p < 0.05) in the two treatment groups were significantly higher than those in the control group. These results suggest that rhubarb has antiatherosclerotic and plaque-stabilizing properties due to antiinflammation and lipid-lowering effects. Copyright © 2008 John Wiley & Sons, Ltd. [source] Local matrix metalloproteinase 2 gene knockdown in balloon-injured rabbit carotid arteries using nonviral-small interfering RNA transfectionTHE JOURNAL OF GENE MEDICINE, Issue 1 2009Hanna Hlawaty Abstract Background Small interfering RNA (siRNA) delivery is a promising approach for the treatment of cardiovascular diseases. Matrix metalloproteinase (MMP) 2 over-expression in the arterial wall has been implicated in restenosis after percutaneous coronary intervention, as well as in spontaneous atherosclerotic plaque rupture. We hypothesized that in vivo local delivery of siRNA targeted at MMP2 (MMP2-siRNA) in the balloon-injured carotid artery of hypercholesterolemic rabbits may lead to inhibition of MMP2 expression. Methods Two weeks after balloon injury, 5 µmol/l of Tamra-tagged MMP2-siRNA, scramble siRNA or saline was locally injected in the carotid artery and incubated for 1 h. Results Fluorescent microscopy studies showed the circumferential uptake of siRNA in the superficial layers of neointimal cells. MMP2 mRNA levels, measured by the real-time reverse transcriptase-polymerase chain reaction, was decreased by 79 ± 25% in MMP2-siRNA- versus scramble siRNA-transfected arteries (p < 0.05). MMP2 activity, measured by gelatin zymography performed on the conditioned media of MMP2-siRNA versus scramble siRNA transfected arteries, decreased by 53 ± 29%, 50 ± 24% and 46 ± 14% at 24, 48 and 72 h, respectively (p < 0.005 for all). No effect was observed on MMP9, pro-MMP9 and TIMP-2 levels. Conclusions The results obtained in the present study suggest that significant inhibition of gene expression can be achieved with local delivery of siRNA in the arterial wall in vivo. Copyright © 2008 John Wiley & Sons, Ltd. [source] Reduction of vascular smooth muscle cell proliferation by immunomodulationBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 4 2001Y. C. Chan Background: Immunological factors may play an important role in mediating the progression of atherosclerosis and myointimal hyperplasia, with heat shock proteins being implicated as possible autoantigens. The authors have shown previously that immunomodulation can reduce vascular smooth muscle cell (vSMC) proliferation following balloon injury to rat carotid arteries. The aim of the present study was to examine the effects of immunomodulatory agents on the proliferation of rat aortic vSMCs remote from the area of balloon injury. The agents used were SRL172 (heat-killed Mycobacterium vaccae) and heat shock protein 65 kDa (HSP65) in Freund's incomplete adjuvant. Both these agents are known to influence T-cell responses. Methods: Male Sprague,Dawley rats were used. All immunizations were given subcutaneously. Four groups were studied (ten animals in each group): group 1 animals were immunized with normal saline, group 2 received SRL172, group 3 SRL172 and HSP65,Freund's, and group 4 HSP65,Freund's. Three immunizations were performed as well as carotid balloon injury. Three animals died, leaving 37 for analysis. Some 5 weeks later the animals were killed and the aorta was harvested. Standard explant techniques were applied to grow aortic vSMCs until confluency, passaged three times, quiesced, and fetal calf serum (FCS) of varying concentrations (0·4,10 per cent) was then added, incubated for another 48 h and cell counts carried out. Results: The proliferation rate of aortic vSMCs in the control group was significantly greater than that in the other study groups (Fig.). While all the treatment groups had significantly less proliferation compared with the control group (*P < 0·05, ,P < 0·01, Mann,Whitney U test), no statistically significant differences existed between any of the study groups. Conclusion: Immunomodulation may result in a reduction of vSMC proliferation. Although the precise mechanisms involved are unclear, these results are in concordance with previous findings that T-cell immunomodulation decreases the development of myointimal hyperplasia after injury, and suggest that a fundamental phenotypic shift has been produced by these immunizations. [source] EARLY ACTIVATION OF INTERNAL MEDIAL SMOOTH MUSCLE CELLS IN THE RABBIT AORTA AFTER MECHANICAL INJURY: RELATIONSHIP WITH INTIMAL THICKENING AND PHARMACOLOGICAL APPLICATIONSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2006Huguette Louis SUMMARY 1Smooth muscle cells (SMC) participate in both inflammatory and dedifferentiation processes during atherosclerosis, as well as during mechanical injury following angioplasty. In the latter, we studied medial SMC differentiation and inflammation processes implicated early after de-endothelialization in relation to mechanical stresses. We hypothesized that activation of a subpopulation of SMC within the media plays a crucial role in the early phase of neointimal formation. 2For this purpose, we used a rabbit model of balloon injury to study activation and differentiation of medial SMC in the early time after denudation and just before neointima thickening. Inflammation was evaluated by the expression of vascular cell adhesion molecule (VCAM)-1, integrin a4b1 and nuclear factor (NF)-kB. Myosin isoforms and 2P1A2 antigen, a membrane protein expressed by rabbit dedifferentiated SMC, were used as markers of differentiation. 3On day 2 after de-endothelialization, VCAM-1, a4b1 and NF-kB were coexpressed by a well-defined subpopulation of SMC of the internal part of the media, in the vicinity of the blood stream. At the same time, the majority of SMC throughout the media expressed non-muscle myosin heavy chain-B (nm-MHC-B) and 2P1A2 antigen. On day 7, when intimal thickening appeared, SMC of the media were no longer activated, whereas some intimal SMC expressed the activation markers. Thus, after de-endothelialization, early dedifferentiation occurs in most of the medial SMC, whereas activation concerned only a subpopulation of SMC located in the internal media. Using the T-type voltage-operated calcium channel blocker mibefradil (0.1,1 mmol/L) in SMC culture, we showed that this agent exhibited an antiproliferative effect in a dose-dependant manner only on undifferentiated cells. 4In conclusion, the results suggest that the activated SMC represent cells that are potentially able to migrate and participate in the intimal thickening process. Thus, the medial SMC inflammatory process, without any contribution of inflammatory cells, may represent a major mechanism underlying the development of intimal thickening following mechanical stress. In humans, inhibition of T-type calcium channels may be a tool to prevent the early proliferation step leading to neointimal formation. [source] | ||||||||||