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Enhanced angiogenesis mediated by vascular endothelial growth factor plasmid-loaded thermoresponsive amphiphilic hydrogel in rat myocardial infarction model
Abstracts / Cardiovascular Revascularization Medicine 10 (2009) 195–212 allows to discriminate lipid-rich from elastin-rich plaques, and (c) OCT calcification detection complements the FLIM biochemical characterization. We are currently building a multimodality OCT/FLIM imaging system that will allow us to thoroughly investigate the advantages of this approach for detecting VP.
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structure of hydrogel. Indeed, a system for controlled release of therapeutic gene may extend the duration of gene expression, especially in the clinical environment where longer gene expression is desirable after single injection. Here, thermoresponsive and biodegradable polymeric hydrogel has been synthesized and investigated for local gene transfer in heart. Methods and Results: Initially, luciferase gene was delivered into mouse heart to test the duration and intensity of gene expression. Gene expression intensity assessed by optical imaging is closely correlated to actual expressed protein concentration measured by luciferase assay. Polymeric hydrogel-based gene transfer was shown to mediate enhanced gene expression up to fourfold, compared to naked plasmid, and have two expression profiles with peaks at 2 days and around 25 days after local injection. Histologic analyses have revealed that high gene expression is initially dominated by myocardium, whereas lower and longer expression is mainly governed by fibrotic and/or inflammatory cells infiltrated into injury site during injection. Enhanced vascular endothelial growth factor (VEGF) expression in infarct region mediated by amphiphilic hydrogel promoted increased capillary density and larger vessel formation, thus enabling efficient angiogenesis. Conclusion: Our study revealed enhanced angiogenesis mediated by VEGF plasmid-loaded thermoresponsive amphiphilic hydrogel in rat myocardial infarction model. doi:10.1016/j.carrev.2009.04.054
Inhibition of toll-like receptor 2 by curcumin reduces the ischemia-reperfusion injury Yong Sook Kim, Jin Sook Kwon, Moon Hwa Hong, Ae Sin Jo, Sun Mi Shin, Myung Ho Jeong, Youngkeun Ahn Chonnam National University Hospital, Gwangju, Republic of Korea
Fig. Histopathology, OCT and FLIM images of the two arteries. doi:10.1016/j.carrev.2009.04.053
Gene Therapy Enhanced angiogenesis mediated by vascular endothelial growth factor plasmid-loaded thermoresponsive amphiphilic hydrogel in rat myocardial infarction model Jin Sook Kwon a, In Kyu Park a, Jung Jun Min a, Myung Ho Jeong a, Won Jong Kim b, Seongbong Jo c, Suzie H Pun d, Jeong Gwan Cho a, Jong Chun Park a, Jung Chaee Kang a, Youngkeun Ahn a a Chonnam National University Hospital, Gwangju, Republic of Korea b Pohang University of Science and Technology, Gwangju, Republic of Korea c University of Mississippi, Mississippi, MS d University of Washington, Seattle, WA Background: Thermoresponsive hydrogel-mediated local gene transfer can be preferentially applied to muscle, since release of DNA into the surrounding tissue can be controlled by three-dimensional network
Background: Toll-like receptors (TLRs) are key mediators of the innate immune system and activated by extracellular stresses such as free radicals, cytokines, or infection. Curcumin, a polyphenolic compound derived from dietary spice turmeric, was reported to be anti-inflammatory and anti-oxidative. We assessed whether curcumin protected cardiac cells via TLR2 inhibition. Methods: Cardiac ischemia-reperfusion injury (IR) was induced in Sprague–Dawley rats. TLR2 was examined by reverse transcriptasepolymerase chain reaction and Western blot. Cardiomyocytes (CMs) were isolated from neonatal rats and stimulated with tumor necrosis factor (TNF)-α (50 ng/ml) and TLR2 agonist peptidoglycan (PGN; 10 μg/ml) in the presence or absence of curcumin (10 μM). To study the effect of curcumin in IR model, the control group received PBS, and curcumin group received 300 mg/kg of curcumin for 1 week before IR injury. After 2 weeks, cardiac fibrosis was assessed by Masson's Trichrome staining, and TLR2 expression level was evaluated by Western blot. Results: In IR rat, TLR2 increased both in infarct and peri-infarct myocardium in 2 weeks, while TLR4 mRNA remained unchanged. TLR2 expression increased in CMs by TNF-α, while TLR4 remained unchanged. In addition, monocyte chemoattractant protein-1, interleukin-6, and plasminogen activator protein-1 were induced by both TNF-α and PGN in CMs, whereas pretreatment of curcumin with CMs blunted their induction significantly. TLR2 mRNA and protein level in infarct myocardium were significantly reduced in curcumin group in compared with control group. Cardiac fibrosis and infiltrated CD68(+) cells were reduced in curcumin group. Conclusion: We suggest that TLR-2 might be an important mediator in response to myocardial ischemic stimulation, and TNF-α might act as a ligand to TLR2 in CMs. The inhibition of TLR2 by curcumin could be proposed as a therapeutic tool. doi:10.1016/j.carrev.2009.04.055
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structure of hydrogel. Indeed, a system for controlled release of therapeutic gene may extend the duration of gene expression, especially in the clinical environment where longer gene expression is desirable after single injection. Here, thermoresponsive and biodegradable polymeric hydrogel has been synthesized and investigated for local gene transfer in heart. Methods and Results: Initially, luciferase gene was delivered into mouse heart to test the duration and intensity of gene expression. Gene expression intensity assessed by optical imaging is closely correlated to actual expressed protein concentration measured by luciferase assay. Polymeric hydrogel-based gene transfer was shown to mediate enhanced gene expression up to fourfold, compared to naked plasmid, and have two expression profiles with peaks at 2 days and around 25 days after local injection. Histologic analyses have revealed that high gene expression is initially dominated by myocardium, whereas lower and longer expression is mainly governed by fibrotic and/or inflammatory cells infiltrated into injury site during injection. Enhanced vascular endothelial growth factor (VEGF) expression in infarct region mediated by amphiphilic hydrogel promoted increased capillary density and larger vessel formation, thus enabling efficient angiogenesis. Conclusion: Our study revealed enhanced angiogenesis mediated by VEGF plasmid-loaded thermoresponsive amphiphilic hydrogel in rat myocardial infarction model. doi:10.1016/j.carrev.2009.04.054
Inhibition of toll-like receptor 2 by curcumin reduces the ischemia-reperfusion injury Yong Sook Kim, Jin Sook Kwon, Moon Hwa Hong, Ae Sin Jo, Sun Mi Shin, Myung Ho Jeong, Youngkeun Ahn Chonnam National University Hospital, Gwangju, Republic of Korea
Fig. Histopathology, OCT and FLIM images of the two arteries. doi:10.1016/j.carrev.2009.04.053
Gene Therapy Enhanced angiogenesis mediated by vascular endothelial growth factor plasmid-loaded thermoresponsive amphiphilic hydrogel in rat myocardial infarction model Jin Sook Kwon a, In Kyu Park a, Jung Jun Min a, Myung Ho Jeong a, Won Jong Kim b, Seongbong Jo c, Suzie H Pun d, Jeong Gwan Cho a, Jong Chun Park a, Jung Chaee Kang a, Youngkeun Ahn a a Chonnam National University Hospital, Gwangju, Republic of Korea b Pohang University of Science and Technology, Gwangju, Republic of Korea c University of Mississippi, Mississippi, MS d University of Washington, Seattle, WA Background: Thermoresponsive hydrogel-mediated local gene transfer can be preferentially applied to muscle, since release of DNA into the surrounding tissue can be controlled by three-dimensional network
Background: Toll-like receptors (TLRs) are key mediators of the innate immune system and activated by extracellular stresses such as free radicals, cytokines, or infection. Curcumin, a polyphenolic compound derived from dietary spice turmeric, was reported to be anti-inflammatory and anti-oxidative. We assessed whether curcumin protected cardiac cells via TLR2 inhibition. Methods: Cardiac ischemia-reperfusion injury (IR) was induced in Sprague–Dawley rats. TLR2 was examined by reverse transcriptasepolymerase chain reaction and Western blot. Cardiomyocytes (CMs) were isolated from neonatal rats and stimulated with tumor necrosis factor (TNF)-α (50 ng/ml) and TLR2 agonist peptidoglycan (PGN; 10 μg/ml) in the presence or absence of curcumin (10 μM). To study the effect of curcumin in IR model, the control group received PBS, and curcumin group received 300 mg/kg of curcumin for 1 week before IR injury. After 2 weeks, cardiac fibrosis was assessed by Masson's Trichrome staining, and TLR2 expression level was evaluated by Western blot. Results: In IR rat, TLR2 increased both in infarct and peri-infarct myocardium in 2 weeks, while TLR4 mRNA remained unchanged. TLR2 expression increased in CMs by TNF-α, while TLR4 remained unchanged. In addition, monocyte chemoattractant protein-1, interleukin-6, and plasminogen activator protein-1 were induced by both TNF-α and PGN in CMs, whereas pretreatment of curcumin with CMs blunted their induction significantly. TLR2 mRNA and protein level in infarct myocardium were significantly reduced in curcumin group in compared with control group. Cardiac fibrosis and infiltrated CD68(+) cells were reduced in curcumin group. Conclusion: We suggest that TLR-2 might be an important mediator in response to myocardial ischemic stimulation, and TNF-α might act as a ligand to TLR2 in CMs. The inhibition of TLR2 by curcumin could be proposed as a therapeutic tool. doi:10.1016/j.carrev.2009.04.055