Inflammation-related induction of absent in melanoma 2 (AIM2) in vascular cells and atherosclerotic lesions suggests a role in vascular pathogenesis

Slides:

Advertisements

Similar presentations

Cyclic adenosine monophosphate response-element binding protein activation by mitogen-activated protein kinase-activated protein kinase 3 and four-and-a-half.

Advertisements

Expression of molecular mediators of apoptosis and their role in the pathogenesis of lower-extremity varicose veins Enrico Ascher, MD, Theresa Jacob,

Vascular endothelial growth factor-C derived from CD11b+ cells induces therapeutic improvements in a murine model of hind limb ischemia Go Kuwahara,

Recovery from hind limb ischemia is less effective in type 2 than in type 1 diabetic mice: Roles of endothelial nitric oxide synthase and endothelial.

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

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

Cyclic adenosine monophosphate response-element binding protein activation by mitogen-activated protein kinase-activated protein kinase 3 and four-and-a-half.

Accelerated aneurysmal dilation associated with apoptosis and inflammation in a newly developed calcium phosphate rodent abdominal aortic aneurysm model

Regulation of vascular smooth muscle cell expression and function of matrix metalloproteinases is mediated by estrogen and progesterone exposure Oscar.

Reduced hind limb ischemia-reperfusion injury in Toll-like receptor-4 mutant mice is associated with decreased neutrophil extracellular traps Rahmi Oklu,

Volume 144, Issue 5, Pages e10 (May 2013)

Elastic fibers reconstructed using adenovirus-mediated expression of tropoelastin and tested in the elastase model of abdominal aortic aneurysm in rats

Undifferentiated mesenchymal stem cells seeded on a vascular prosthesis contribute to the restoration of a physiologic vascular wall Alain Mirza, MD,

Yi-kuan Chen, MD, Xue-mei Jiang, MSc, Jian-ping Gong, MD

Differential expression of Hedgehog/Notch and transforming growth factor-β in human abdominal aortic aneurysms Adam J. Doyle, MD, Eileen M. Redmond,

Growth hormone–releasing peptide ghrelin inhibits homocysteine-induced endothelial dysfunction in porcine coronary arteries and human endothelial cells

The therapeutic effect of vascular endothelial growth factor gene- or heme oxygenase-1 gene-modified endothelial progenitor cells on neovascularization.

Endogenous superoxide dismutase activation by oral administration of riboflavin reduces abdominal aortic aneurysm formation in rats Zhenhai Yu, MD, Keisuke.

Xue Ma, MD, Jeffrey D. Pearce, MD, David B. Wilson, MD, William P

Smooth muscle cells from abdominal aortic aneurysms are unique and can independently and synergistically degrade insoluble elastin Nathan Airhart, MD,

Hyperphosphatemia induces protective autophagy in endothelial cells through the inhibition of Akt/mTOR signaling Yu-Juei Hsu, MD, PhD, Shih-Che Hsu,

Transglutaminase type 2 in human abdominal aortic aneurysm is a potential factor in the stabilization of extracellular matrix Sung Shin, MD, Yong-Pil.

Tissue engineering applications to vascular bypass graft development: The use of adipose-derived stem cells Paul DiMuzio, MD, Thomas Tulenko, PhD Journal.

Gene transduction into aortic wall using plasmid-loaded cationized gelatin hydrogel- coated polyester stent graft Hongshan Zhong, MD, Osamu Matsui, MD,

Michael A. Rosenbaum, MD, Pinaki Chaudhuri, PhD, Linda M. Graham, MD

Hyperphosphatemia induces protective autophagy in endothelial cells through the inhibition of Akt/mTOR signaling Yu-Juei Hsu, MD, PhD, Shih-Che Hsu,

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

Gene transduction into aortic wall using plasmid-loaded cationized gelatin hydrogel- coated polyester stent graft Hongshan Zhong, MD, Osamu Matsui, MD,

Human renal epithelial cells produce the long pentraxin PTX3

Volume 115, Issue 6, Pages (December 1998)

Vascular smooth muscle cell peroxisome proliferator-activated receptor-γ deletion promotes abdominal aortic aneurysms Milton Hamblin, PhD, Lin Chang,

Zhuo Li, Dieter Metze, Dorothea Nashan, Carsten Müller-Tidow, Hubert L

Volume 69, Issue 8, Pages (April 2006)

Association of smooth muscle cell phenotypes with extracellular matrix disorders in thoracic aortic dissection Lixin Wang, MD, PhD, Jing Zhang, MD, PhD,

Transforming growth factor-β increases vascular smooth muscle cell proliferation through the Smad3 and extracellular signal-regulated kinase mitogen-activated.

Aromatase is required for female abdominal aortic aneurysm protection

Α1-Adrenergic receptors mediate combined signals initiated by mechanical stretch stress and norepinephrine leading to accelerated mouse vein graft atherosclerosis

Adventitial delivery of platelet-derived endothelial cell growth factor gene prevented intimal hyperplasia of vein graft Mitsuteru Handa, MD, Wei Li,

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

Increased connexin43 expression in human saphenous veins in culture is associated with intimal hyperplasia Sébastien Déglise, MD, David Martin, MS, Hervé.

Orally administered dipeptidyl peptidase-4 inhibitor (alogliptin) prevents abdominal aortic aneurysm formation through an antioxidant effect in rats

Differential expression of elastin assembly genes in patients with Stanford Type A aortic dissection using microarray analysis Bernice L.Y. Cheuk, PhD,

Long-term patency of small-diameter vascular graft made from fibroin, a silk-based biodegradable material Soichiro Enomoto, MD, PhD, Makoto Sumi, MD,

Thomas E. Arnold, MD, Dmitri Gnatenko, PhD, Wadie F. Bahou, MD

Ascending aorta dilation in association with bicuspid aortic valve: A maturation defect of the aortic wall Nimrat Grewal, MD, Adriana C. Gittenberger-de.

Volume 87, Issue 2, Pages (February 2015)

Murine abdominal aortic aneurysm model by orthotopic allograft transplantation of elastase-treated abdominal aorta Zhenjie Liu, MD, PhD, Qiwei Wang,

Overexpression of transforming growth factor–β1 correlates with increased synthesis of nitric oxide synthase in varicose veins Theresa Jacob, PhD, Anil.

Aging exacerbates neointimal formation, and increases proliferation and reduces susceptibility to apoptosis of vascular smooth muscle cells in mice Roberto.

Pingping Ren, MD, Lin Zhang, MS, Gaiping Xu, MD, Laura C

Magnetic nanosphere-guided site-specific delivery of vascular endothelial growth factor gene attenuates restenosis in rabbit balloon-injured artery Tiemin.

Midkine is expressed by infiltrating macrophages in in-stent restenosis in hypercholesterolemic rabbits Hiroshi Narita, MD, Sen Chen, PhD, Kimihiro Komori,

Enhanced expression of glucose transporter-1 in vascular smooth muscle cells via the Akt/tuberous sclerosis complex subunit 2 (TSC2)/mammalian target.

PD-L1 Is Upregulated by Simultaneous Amplification of the PD-L1 and JAK2 Genes in Non–Small Cell Lung Cancer Seiichi Ikeda, MSc, Tatsuro Okamoto, MD,

The pathophysiology of abdominal aortic aneurysm growth: Corresponding and discordant inflammatory and proteolytic processes in abdominal aortic and popliteal.

Role of hemodynamic forces in the ex vivo arterialization of human saphenous veins Xavier Berard, MD, PhD, Sébastien Déglise, MD, Florian Alonso, PhD,

Adventitial delivery of platelet-derived endothelial cell growth factor gene prevented intimal hyperplasia of vein graft Mitsuteru Handa, MD, Wei Li,

Volume 70, Issue 7, Pages (October 2006)

Paola Zigrino, Isolde Kuhn, Tobias Bäuerle, Jan Zamek, Jay W

Recovery from hind limb ischemia is less effective in type 2 than in type 1 diabetic mice: Roles of endothelial nitric oxide synthase and endothelial.

Characterization of primary and restenotic atherosclerotic plaque from the superficial femoral artery: Potential role of Smad3 in regulation of SMC proliferation

Volume 10, Issue 1, Pages (July 2009)

Lisheng Zhang, MD, Leigh Brian, MS, Neil J. Freedman, MD

Role of NF-κB Activity in Apoptotic Response of Keratinocytes Mediated by Interferon-γ, Tumor Necrosis Factor-α, and Tumor-Necrosis-Factor-Related Apoptosis-Inducing.

In vitro differences between smooth muscle cells derived from varicose veins and normal veins Ying Xiao, PhD, Zhibin Huang, MD, Henghui Yin, PhD, Ying.

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

Increased Expression of Wnt2 and SFRP4 in Tsk Mouse Skin: Role of Wnt Signaling in Altered Dermal Fibrillin Deposition and Systemic Sclerosis Julie Bayle,

Identification and characterization of microRNAs in vascular smooth muscle cells from patients with abdominal aortic aneurysms Bernice Lai Yee Cheuk,

Recovery from hind limb ischemia is less effective in type 2 than in type 1 diabetic mice: Roles of endothelial nitric oxide synthase and endothelial.

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

Presentation transcript:

Inflammation-related induction of absent in melanoma 2 (AIM2) in vascular cells and atherosclerotic lesions suggests a role in vascular pathogenesis Maani Hakimi, MD, Andreas Peters, MD, Anja Becker, Dittmar Böckler, MD, Susanne Dihlmann, PhD Journal of Vascular Surgery Volume 59, Issue 3, Pages 794-803.e2 (March 2014) DOI: 10.1016/j.jvs.2013.03.048 Copyright © 2014 Society for Vascular Surgery Terms and Conditions

Fig 1 Absent in melanoma 2 (AIM2) transcript expression in human aortic endothelial and smooth muscle cells in response to inflammatory cytokines illustrating the time-dependent induction of AIM2 in each of the cell types. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression of corresponding samples is shown for control to demonstrate that equal amounts of total complementary DNA were analyzed, independent of cell viability. A, End-point reverse-transcription polymerase chain reaction of tumor necrosis factor (TNF)-α–stimulated (upper panel) and interferon (IFN)-γ–stimulated (lower panel) human aortic endothelial cells (HAoEC), smooth muscle cells (HAoSMC), and in the aortic vascular smooth muscle cell line (T/G-HA-VSMC). B, Quantitative real-time reverse transcription polymerase chain reaction of the same cells as in A. Fold-AIM2 expression is shown relative to expression of 18s RNA in corresponding samples. The bars and error bars represent the mean and standard deviation, respectively, of triplicate analysis. *P < .05; **P < .01 (paired t-test) 0*: cells were grown without media replacement for 96 hours. Journal of Vascular Surgery 2014 59, 794-803.e2DOI: (10.1016/j.jvs.2013.03.048) Copyright © 2014 Society for Vascular Surgery Terms and Conditions

Fig 2 Expression of (A) absent in melanoma 2 (AIM2) transcript and (B) protein in human aortic smooth muscle cells (HAoSMC) upon stimulation with foreign double-stranded DNA (poly(dA:dT)) with or without previous stimulation with interferon (IFN)-γ. A, Little AIM2 expression is detected in unstimulated cells, which is markedly upregulated upon transfection of the cells with poly(dA:dT) and pretreatment of the cells with IFN-γ. B, The inflammasome component ASC is expressed in HAoSMC and in the aortic vascular smooth muscle cell line (T/G-HA-VSMC) at levels that are not affected by cytoplasmic double-stranded DNA or IFN-γ. AIM2 protein expression is below detection level in HAoSMC and T/G-HA-VSMC. Journal of Vascular Surgery 2014 59, 794-803.e2DOI: (10.1016/j.jvs.2013.03.048) Copyright © 2014 Society for Vascular Surgery Terms and Conditions

Fig 3 Absent in melanoma 2 (AIM2) expression pattern is shown in human arterial wall. Formalin-fixed paraffin-embedded sections were immunohistochemically stained for AIM2, CD31, and smooth muscle actin (SMA). A, Normal, nonatherosclerotic carotid artery. B, Normal, nonatherosclerotic aorta. Ad, Adventitia; EC, endothelial cells; I, intima; M, media. Original magnification, ×4, ×10, or ×200, respectively, as indicated. Examples from 10 normal arterial samples are shown, with red indicating positive immunostaining and blue indicating nuclei and connective tissue. Journal of Vascular Surgery 2014 59, 794-803.e2DOI: (10.1016/j.jvs.2013.03.048) Copyright © 2014 Society for Vascular Surgery Terms and Conditions

Fig 4 Absent in melanoma 2 (AIM2) expression pattern is shown in lesions derived from (A) abdominal aortic aneurism (AAA) and (B) atherosclerotic carotid artery. A, AIM2 expression is increased in smooth muscle actin (SMA)-positive cells of the intima/media (lesion 1) and of the vasa vasorum (lesions 2 and 3; adventitia) of AAA, whereas it is absent in the SMA-positive intima/media of lesion 4. B, Atherosclerotic carotid lesions show that AIM2 expression accumulates in cells surrounding necrotic and calcified (**) areas or cholesterol (Ch) within the intima/media. Examples of four AAA samples and 20 atherosclerotic carotid samples are shown, with red indicating positive immunostaining and blue indicating nuclei and connective tissue. Original magnification, ×100. Journal of Vascular Surgery 2014 59, 794-803.e2DOI: (10.1016/j.jvs.2013.03.048) Copyright © 2014 Society for Vascular Surgery Terms and Conditions

Fig 5 Western blot analysis for absent in melanoma 2 (AIM2) protein expression in (A) primary human aortic endothelial cells (HAoEC), (B) primary human aortic smooth muscle cells (HAoSMC), and (C) the aortic vascular smooth muscle cell line (T/G-HA-VSMC). Cells were analyzed in response to the inflammatory cytokines tumor necrosis factor (TNF)-α and interferon (IFN)-γ. Lysates were derived from cells stimulated in parallel to the cells used in Fig 1. Differentiated THP-1 cells were transfected with poly(dA:dT), as described in the Methods section, and used as a positive control. Protein loading was assessed by actin expression. Journal of Vascular Surgery 2014 59, 794-803.e2DOI: (10.1016/j.jvs.2013.03.048) Copyright © 2014 Society for Vascular Surgery Terms and Conditions

Supplementary Fig 1 (online only) Induction absent in melanoma 2 (AIM2) transcript expression by cytoplasmic DNA in HT-29 colorectal cancer cells. Reverse transcription polymerase chain reaction was performed as described earlier.18 GAPDH, Glyceraldehyde-3-phosphate dehydrogenase; IFN, interferon. Journal of Vascular Surgery 2014 59, 794-803.e2DOI: (10.1016/j.jvs.2013.03.048) Copyright © 2014 Society for Vascular Surgery Terms and Conditions

Supplementary Fig 2 (online only) Characterization of anti-absent in melanoma 2 (AIM2) antibody for immunohistochemical analysis. A, For characterization of AIM2 detection by the anti-AIM2 antibody, 293T cells were transfected with empty enhanced green fluorescent protein (EGFP) vector or a plasmid encoding EGFP-AIM2-fusion protein. Cells were formalin-fixed, precipitated in bovine serum albumin, and embedded in paraffin according to standard procedures. Immunohistochemistry was performed as described in the Methods section. Dilution of anti-AIM2: 1:150. B, Detection of AIM2 in single cells of a lymph node. Dilution of anti-AIM2: 1:150. C, Detection of AIM2 in normal small intestinal epithelium. Strong cytoplasmic expression of AIM2 is detectable in epithelial cells lining the lumen. Dilution of anti-AIM2: 1:150. Original magnification ×40 or ×200, as indicated. Journal of Vascular Surgery 2014 59, 794-803.e2DOI: (10.1016/j.jvs.2013.03.048) Copyright © 2014 Society for Vascular Surgery Terms and Conditions