Attenuation of early atherosclerotic lesions by immunotolerance with β2 glycoprotein I and the immunomodulatory effectors interleukin 2 and 10 in a murine.

Slides:

Advertisements

Similar presentations

Prevention of atherosclerosis by the mTOR inhibitor everolimus in LDLR−/− mice despite severe hypercholesterolemia Marc A. Mueller, Frank Beutner, Daniel.

Advertisements

Local lentiviral short hairpin RNA silencing of CCR2 inhibits vein graft thickening in hypercholesterolemic apolipoprotein E3-Leiden mice Daniël Eefting,

Diet-induced obesity drives negative mouse vein graft wall remodeling

Mesenchymal stem cells attenuate angiotensin II-induced aortic aneurysm growth in apolipoprotein E-deficient mice Ryotaro Hashizume, MD, Aika Yamawaki-Ogata,

Jeanwan Kang, MD, Hassan Albadawi, MD, Patrick J. Casey, MD, Thomas A

Castration of male mice prevents the progression of established angiotensin II-induced abdominal aortic aneurysms Xuan Zhang, PhD, Sean Thatcher, PhD,

In vivo electroporation of constitutively expressed HIF-1α plasmid DNA improves neovascularization in a mouse model of limb ischemia Geoffrey O. Ouma,

Elevation of hemopexin-like fragment of matrix metalloproteinase-2 tissue levels inhibits ischemic wound healing and angiogenesis April E. Nedeau, MD,

Pharmacologic blockade and genetic deletion of androgen receptor attenuates aortic aneurysm formation John P. Davis, MD, Morgan Salmon, PhD, Nicolas.

Hyperglycemia limits experimental aortic aneurysm progression

Rapid dilation of the abdominal aorta during infusion of angiotensin II detected by noninvasive high-frequency ultrasonography Chiara Barisione, BSc,

Fucoidan interferes with Porphyromonas gingivalis-induced aneurysm enlargement by decreasing neutrophil activation Jean-Marc Alsac, MD, Sandrine Delbosc,

Preparation and characterization of injectable fibrillar type I collagen and evaluation for pseudoaneurysm treatment in a pig model Paul J. Geutjes,

Loss of STAT1 is associated with increased aortic rupture in an experimental model of aortic dissection and aneurysm formation Matthew J. Eagleton, MD,

Plaque in superficial femoral arteries indicates generalized atherosclerosis and vulnerability to coronary death: An autopsy study Søren Dalager, MD,

Tamoxifen up-regulates catalase production, inhibits vessel wall neutrophil infiltration, and attenuates development of experimental abdominal aortic.

The wrapping method using biodegradable felt strips has a preventive effect on the thinning of the aortic wall: Experimental study in the canine aorta

Circulating anti-β2-glycoprotein I antibodies of peripheral arterial disease patients trigger a genomic overexpression of Toll-like receptor 4 in endothelial.

Local lentiviral short hairpin RNA silencing of CCR2 inhibits vein graft thickening in hypercholesterolemic apolipoprotein E3-Leiden mice Daniël Eefting,

Robert E. Merritt, MD, Reiko E. Yamada, BA, Nabil Wasif, MD, Ronald G

Paul Cronin, MD, MS, Gilbert R. Upchurch, MD, Himanshu J. Patel, MD, G

Modification of the descending thoracic aortic anastomotic site using biodegradable felt: Study in a canine model with or without basic fibroblast growth.

Ethyl pyruvate modulates delayed paralysis following thoracic aortic ischemia reperfusion in mice Bao-Ngoc Nguyen, MD, Hassan Albadawi, MD, Rahmi Oklu,

Controlled release of ascorbic acid from gelatin hydrogel attenuates abdominal aortic aneurysm formation in rat experimental abdominal aortic aneurysm.

Hemagglutinating virus of Japan-liposome–mediated gene transfer of endothelial cell nitric oxide synthase inhibits intimal hyperplasia of canine vein.

Interleukin 18 binding protein (IL18-BP) inhibits neointimal hyperplasia after balloon injury in an atherosclerotic rabbit model Jian-Ming Li, MD, Mohammad.

Aromatase is required for female abdominal aortic aneurysm protection

Adenovirus-mediated intra-arterial delivery of cellular repressor of E1A-stimulated genes inhibits neointima formation in rabbits after balloon injury

Suppression of experimental abdominal aortic aneurysms in mice by treatment with pyrrolidine dithiocarbamate, an antioxidant inhibitor of nuclear factor-κB

Free-radical scavenger edaravone inhibits both formation and development of abdominal aortic aneurysm in rats Keisuke Morimoto, MD, Tomomi Hasegawa,

Potential role of erythropoietin receptors and ligands in attenuating apoptosis and inflammation in critical limb ischemia Dhiraj Joshi, MD, MRCS, David.

Aneurysm formation in experimental atherosclerosis: Relationship to plaque evolution Christopher K. Zarins, MD, Seymour Glagov, MD, Dragoslava Vesselinovitch,

Diet-induced obesity drives negative mouse vein graft wall remodeling

Vascular endothelial growth factor naked DNA gene transfer enhances thrombus recanalization and resolution Matthew Waltham, MA, PhD, Kevin Burnand, MS,

S-phase kinase-associated protein-2 (Skp2) promotes vascular smooth muscle cell proliferation and neointima formation in vivo Yih-Jer Wu, MD, PhD, Graciela.

Enhanced Cutaneous Inflammatory Reactions to Aspergillus fumigatus in a Murine Model of Chronic Granulomatous Disease Jeffrey E. Petersen Journal of.

Michael A. Rosenbaum, MD, Keiko Miyazaki, MD, Scott M. Colles, Linda M

Vascular calcification is dependent on plasma levels of pyrophosphate

Spatiotemporal expression and localization of matrix metalloproteinas-9 in a murine model of thoracic aortic aneurysm Jeffrey A. Jones, PhD, John R.

Nicolas H. Pope, MD, Morgan Salmon, PhD, William F

Impaired graft healing due to hypercholesterolemia is prevented by dietary supplementation with α-tocopherol Keiko Miyazaki, MD, Scott M. Colles, PhD,

Leptin receptor is elevated in carotid plaques from neurologically symptomatic patients and positively correlated with augmented macrophage density Jacob.

Cigarette smoking increases aortic dilatation without affecting matrix metalloproteinase- 9 and -12 expression in a modified mouse model of aneurysm formation

Intimal angiosarcoma presenting with common femoral artery aneurysm

Prediction of asymptomatic abdominal aortic aneurysm expansion by means of rate of variation of C-reactive protein plasma levels Joaquin De Haro, MD,

Gary R. Seabrook, MD Journal of Vascular Surgery

In vivo suppression of vein graft disease by nonviral, electroporation-mediated, gene transfer of tissue inhibitor of metalloproteinase-1 linked to the.

Interleukin-1 receptor antagonist attenuates the severity of spinal cord ischemic injury in rabbits Satoshi Akuzawa, MD, Teruhisa Kazui, MD, PhD, Enyi.

Adventitial endothelial implants reduce matrix metalloproteinase-2 expression and increase luminal diameter in porcine arteriovenous grafts Helen M.

A novel rat model of abdominal aortic aneurysm using a combination of intraluminal elastase infusion and extraluminal calcium chloride exposure Akiko.

Exploration of the mechanisms by which 3,4-benzopyrene promotes angiotensin II- induced abdominal aortic aneurysm formation in mice Kangting Ji, MD, Yong.

Dose-dependent neuroprotection of delta-opioid peptide [D-Ala2, D-Leu5] enkephalin on spinal cord ischemia-reperfusion injury by regional perfusion into.

Murine ultrasound imaging for circumferential strain analyses in the angiotensin II abdominal aortic aneurysm model John T. Favreau, BS, Binh T. Nguyen,

Extracorporeal shock wave therapy ameliorates secondary lymphedema by promoting lymphangiogenesis Masayuki Kubo, PhD, Tao-Sheng Li, MD, PhD, Takahiro.

Loss of lymphatic vessels and regional lipid accumulation is associated with great saphenous vein incompetence Hiroki Tanaka, MD, Nobuhiro Zaima, PhD,

Interleukin-18 and the Costimulatory Molecule B7-1 Have a Synergistic Anti-Tumor Effect on Murine Melanoma; Implication of Combined Immunotherapy for.

Comparison of the vascular responses to balloon-expandable stenting in the coronary and peripheral circulations: Long-term results in an animal model.

Cathepsin G deficiency reduces periaortic calcium chloride injury-induced abdominal aortic aneurysms in mice Jing Wang, MD, PhD, Galina K. Sukhova, PhD,

Restoration of left ventricular geometry and improvement of left ventricular function in a rodent model of chronic ischemic cardiomyopathy Jiashing Yu,

A prospective randomized controlled study with intermittent mechanical compression of the calf in patients with claudication Joaquin de Haro, MD, Francisco.

Free radical attenuation prevents thrombosis and enables photochemical inhibition of vein graft intimal hyperplasia Giuseppe R Nigri, MD, PhD, Sylvie.

The matrix metalloproteinase inhibitor BB-94 limits expansion of experimental abdominal aortic aneurysms David A. Bigatel, MD, James R. Elmore, MD, David.

Blockade of monocyte chemoattractant protein-1 by adenoviral gene transfer inhibits experimental vein graft neointimal formation Hideki Tatewaki, MD,

Wanfen Xiong, MD, PhD, Rebecca Knispel, BS, Jason Mactaggart, MD, B

Short-term dexamethasone treatment inhibits vein graft thickening in hypercholesterolemic ApoE3Leiden transgenic mice Abbey Schepers, MD, Nuno M.M. Pires,

Activation of transglutaminase type 2 for aortic wall protection in a rat abdominal aortic aneurysm formation Takashi Munezane, MD, Tomomi Hasegawa,

Circumferential heterogeneity in the abdominal aortic aneurysm wall composition suggests lateral sides to be more rupture prone Rob Hurks, MD, Gerard.

Adenoviral-mediated uteroglobin gene transfer inhibits neointimal hyperplasia after balloon injury in the rat carotid artery Robert A. Larson, MD, Mina.

Aspirin therapy inhibits NLRP1 (nucleotide-binding domain-like receptor protein 1) inflammasome gene expression in patients with peripheral artery disease

A novel rat model of abdominal aortic aneurysm using a combination of intraluminal elastase infusion and extraluminal calcium chloride exposure Akiko.

Presentation transcript:

Attenuation of early atherosclerotic lesions by immunotolerance with β2 glycoprotein I and the immunomodulatory effectors interleukin 2 and 10 in a murine model Joaquin De Haro, MD, Leticia Esparza, MD, Silvia Bleda, MD, Cesar Varela, MD, Carolina Sanchez, PhD, Francisco Acin, MD, PhD Journal of Vascular Surgery Volume 62, Issue 6, Pages 1625-1631 (December 2015) DOI: 10.1016/j.jvs.2014.05.096 Copyright © 2015 Society for Vascular Surgery Terms and Conditions

Fig 1 Thoracic aorta thickening was significantly inhibited in all groups immunized with β2-glycoprotein I (β2-GPI) compared with the control group. Eight-week-old low-density lipoprotein-receptor deficient (LDLR−/−) mice were treated with a high-fat diet for 1 week before inoculation and then continued on the diet for 8 weeks. To quantify thoracic aorta thickening, tissue segments were harvested after in vitro perfusion fixation with 4% formaldehyde, fixed overnight, and embedded in paraffin. Sequential cross-sections were made throughout the embedded aorta samples. For each animal, six representative sections per vessel segment were used after being stained with hematoxylin and eosin. Aorta thickening was defined as the area between the lumen and adventitia, and determined by subtracting the luminal area from the total vessel wall area. Namely, the thickness of the aortic wall of the control group was significantly higher compared with the groups that were immunized with β2-GPI, β2-GPI plus interleukin (IL)-2, β2-GPI plus IL-10, and β2-GPI plus IL-2 plus IL-10 (0.43 ± 0.002 vs 0.29 ± 0.002 mm2; P = .001). A, Thoracic aorta thickening was increased in the control group, which received phoshpate-buffered saline (PBS) inoculation, compared with the immunized groups, in which mice received one intravenous injection with β2-GPI (5 μg) loaded with or without IL-2 (1 μg) or IL-10 (5 μg), or both. Bar graphs show mean ± standard error of the mean (error bars). *P = .001 immunized experimental groups vs control (n = 24 for each experimental group) by Wilcoxon test. B and C, a, control; b, immunized, hematoxylin and eosin stain. The arrows in C mean internal and xternal diameter of the aorta. Journal of Vascular Surgery 2015 62, 1625-1631DOI: (10.1016/j.jvs.2014.05.096) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

Fig 2 The atheroprotective effect of immunization with β2-glycoprotein I (β2-GPI) was enhanced by a single-dose injection of interleukin (IL)-2 or IL-10, or both. The inoculation with β2-GPI plus IL-2 and with β2-GPI plus IL-10 produced no differences in the aorta thickening among the groups. No differences were found when the group that received β2-GPI plus IL-2 plus IL10 was compared with the groups injected with β2-GPI and the two cytokines separately. Thoracic aorta thickening is shown in groups immunized with β2-GPI only (β2-GPI), β2-GPI associated with IL-2 (β2-GPI+IL-2), along with IL-10 (β2-GPI+Il-10), and with IL-2 and IL-10 (β2-GPI +IL-2+IL-10). The mice received one intravenous injection with β2-GPI (5 μg) loaded with or without IL-2 (1 μg) or IL-10 (5 μg), or both, and were fed a cholesterol-rich high-saturated-fat diet for 8 weeks. Bar graphs show mean ± standard error of the mean (error bars). *P = .001 β2-GPI vs β2-GPI+IL-2; β2-GPI vs β2-GPI+IL-10. †P = .62 β2-GPI+IL-2 vs β2-GPI+IL-10 vs β2-GPI+IL-2+IL-10 (n = 6 for each experimental group) by analysis of variance and the Tukey honest significant difference multiple comparison test. Journal of Vascular Surgery 2015 62, 1625-1631DOI: (10.1016/j.jvs.2014.05.096) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

Fig 3 β2-glycoprotein I (β2-GPI) immunotolerance and the immunomodulatory effectors interleukin (IL)-2 and IL-10 attenuates atherosclerotic lesions in low-density lipoprotein receptor-deficient (LDLR−/−) mice. Aortic root lesions were assessed by measurement of the lumen diameter divided by the total vessel diameter, constituting the ratio lumen/total cross-sectional area, as an objective estimate of the size of the fatty streaks. The ratio lumen/total vessel sectional area of the aorta was significantly increased in the immunized groups compared with the control group (0.85 ± 0.05 vs 0.79 ± 0.04, respectively; P < .001). Bar graphs show lumen/total vessel area ratio of the control group, which received phosphate-buffered saline (PBS) inoculation, and immunized groups that received one intravenous injection with β2-GPI (5 μg) loaded with or without IL-2 (1 μg) or IL-10 (5 μg), or both, and were fed a cholesterol-rich high-saturated-fat diet for 8 weeks. Bar graphs show mean ± standard error of the mean (error bars). *P = .001 immunized experimental groups vs control (n = 24 for each experimental group) by Student t-test. Journal of Vascular Surgery 2015 62, 1625-1631DOI: (10.1016/j.jvs.2014.05.096) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

Fig 4 Atherosclerotic lesion attenuation by immunization with β2-glycoprotein I (β2-GPI) was enhanced by immunomodulation by a single-dose injection of interleukine (IL)-2 or IL-10, or both, in low-density lipoprotein receptor-deficient (LDLR−/−) mice. The inoculation with β2-GPI plus IL-2 (β2-GPI+IL-2), β2-GPI plus IL-10 (β2-GPI+IL-10), and β2-GPI plus IL-2 plus IL-10 (β2-GPI+IL-2+IL-10) produced no differences in the assessment of atherosclerotic lesions when the groups were compared. Lesion size in the aortic root was assessed by measurement of the lumen diameter divided by the total vessel diameter, constituting the ratio lumen/total cross sectional area, as an objective estimate of the size of the fatty streaks. The lumen/total vessel ratio is shown for the β2-GPI, β2-GPI+IL-2, β2-GPI+Il-10, and β2-GPI +IL-2+IL-10 groups. The mice received one intravenous injection with β2-GPI (5 μg) loaded with or without IL-2 (1 μg) or IL-10 (5 μg), or both, and were fed a cholesterol-rich high-saturated-fat diet for 8 weeks. Bar graphs show mean ± standard error of the mean (error bars). *P < .001 β2-GPI vs β2-GPI+IL-2; β2-GPI vs β2-GPI+IL-10. †P = .39 β2-GPI+IL-2 vs β2-GPI+IL-10 vs β2-GPI+IL-2+IL-10 (n = 6 for each experimental group) by analysis of variance and the Tukey multiple comparison test. Journal of Vascular Surgery 2015 62, 1625-1631DOI: (10.1016/j.jvs.2014.05.096) Copyright © 2015 Society for Vascular Surgery Terms and Conditions