Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:456-461
doi: 10.1161/hq0302.104905
doi: 10.1161/hq0302.104905
© 2002 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Interleukin-4 Deficiency Decreases Atherosclerotic Lesion Formation in a Site-Specific Manner in Female LDL Receptor-/- Mice
From the Gill Heart Institute (V.L.K., A.D.), Division of Cardiovascular Medicine, and the Blood and Marrow Transplant Program (S.J.S.), Division of Hematology/Oncology, University of Kentucky, Lexington.
Correspondence to Alan Daugherty, PhD, Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, KY 40536. E-mail adaugh{at}pop.uky.edu
Activated lymphocytes and mast cells have been detected in human atherosclerotic lesions. Interleukin-4 (IL-4) is a prominent cytokine released during the activation of both these cell types, and its mRNA has been detected in human and mouse atherosclerotic lesions. To define the effects of IL-4 on atherogenesis, bone marrow stem cells from either IL-4-/- or IL-4+/+ mice were transplanted into lethally irradiated female low density lipoprotein (LDL) receptor-/- mice. After an interval sufficient to allow engraftment, mice were placed on a diet containing 21% saturated fat, 1.25% cholesterol, and 0.5% cholate. Hematopoietic engraftment was confirmed by the presence of the LDL receptor gene in bone marrow cells. The effect on IL-4 depletion was confirmed by quantifying cytokine release from splenocytes of reconstituted mice. The deficiency of IL-4 in bone marrow–derived cells had no effect on serum cholesterol concentrations or on the distribution of cholesterol among lipoproteins. Atherosclerotic lesion formation was not changed in the aortic root. However, deficiency of IL-4 led to reduced lesion size in the arch (9.1±1.1% versus 2.8±0.8% of intimal area, P<0.001) and the thoracic aorta (1.2±0.2% versus 0.4±0.1%, P<0.002). Therefore, IL-4 deficiency reduced atherosclerotic lesion formation in a site-specific manner in female LDL receptor-/- mice fed a high-fat diet.
Key Words: atherosclerosis • bone marrow transplant • interleukin-4 • low density lipoprotein receptors • T lymphocytes
This article has been cited by other articles:
 |
|
 |
|
  B. Boyanovsky, M. Zack, K. Forrest, and N. R. Webb The Capacity of Group V sPLA2 to Increase Atherogenicity of ApoE-/- and LDLR-/- Mouse LDL In Vitro Predicts its Atherogenic Role In Vivo Arterioscler. Thromb. Vasc. Biol., April 1, 2009; 29(4): 532 - 538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Mallat, S. Taleb, H. Ait-Oufella, and A. Tedgui The role of adaptive T cell immunity in atherosclerosis J. Lipid Res., April 1, 2009; 50(Supplement): S364 - S369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. L. King, A. Y. Lin, F. Kristo, T. J.T. Anderson, N. Ahluwalia, G. J. Hardy, A. P. Owens III, D. A. Howatt, D. Shen, A. M. Tager, et al. Interferon-{gamma} and the Interferon-Inducible Chemokine CXCL10 Protect Against Aneurysm Formation and Rupture Circulation, January 27, 2009; 119(3): 426 - 435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Wong, M. Freiberg, R. Tracy, and L. Kuller Epidemiology of Cytokines: The Women On the Move through Activity and Nutrition (WOMAN) Study Am. J. Epidemiol., August 15, 2008; 168(4): 443 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Kleemann, S. Zadelaar, and T. Kooistra Cytokines and atherosclerosis: a comprehensive review of studies in mice Cardiovasc Res, August 1, 2008; 79(3): 360 - 376. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Schulte, G. K. Sukhova, and P. Libby Genetically Programmed Biases in Th1 and Th2 Immune Responses Modulate Atherogenesis Am. J. Pathol., June 1, 2008; 172(6): 1500 - 1508. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nachtigal, A. Ghaffar, and E. P. Mayer Galectin-3 Gene Inactivation Reduces Atherosclerotic Lesions and Adventitial Inflammation in ApoE-Deficient Mice Am. J. Pathol., January 1, 2008; 172(1): 247 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. L. King, L. A. Cassis, and A. Daugherty Interleukin-4 Does Not Influence Development of Hypercholesterolemia or Angiotensin II-Induced Atherosclerotic Lesions in Mice Am. J. Pathol., December 1, 2007; 171(6): 2040 - 2047. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Gautier, T. Huby, B. Ouzilleau, C. Doucet, F. Saint-Charles, G. Gremy, M. J. Chapman, and P. Lesnik Enhanced Immune System Activation and Arterial Inflammation Accelerates Atherosclerosis in Lupus-Prone Mice Arterioscler. Thromb. Vasc. Biol., July 1, 2007; 27(7): 1625 - 1631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Bostrom, B. B. Boyanovsky, C. T. Jordan, M. P. Wadsworth, D. J. Taatjes, F. C. de Beer, and N. R. Webb Group V Secretory Phospholipase A2 Promotes Atherosclerosis: Evidence From Genetically Altered Mice Arterioscler. Thromb. Vasc. Biol., March 1, 2007; 27(3): 600 - 606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Cassis, D. L. Rateri, H. Lu, and A. Daugherty Bone Marrow Transplantation Reveals That Recipient AT1a Receptors Are Required to Initiate Angiotensin II-Induced Atherosclerosis and Aneurysms Arterioscler. Thromb. Vasc. Biol., February 1, 2007; 27(2): 380 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. W. Parks, A. J. Lusis, and J. H.S. Kabarowski Loss of the Lysophosphatidylcholine Effector, G2A, Ameliorates Aortic Atherosclerosis in Low-Density Lipoprotein Receptor Knockout Mice Arterioscler. Thromb. Vasc. Biol., December 1, 2006; 26(12): 2703 - 2709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-K. L. Robertson and G. K Hansson T Cells in Atherogenesis: For Better or For Worse? Arterioscler. Thromb. Vasc. Biol., November 1, 2006; 26(11): 2421 - 2432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zernecke, E. A. Liehn, J.-L. Gao, W. A. Kuziel, P. M. Murphy, and C. Weber Deficiency in CCR5 but not CCR1 protects against neointima formation in atherosclerosis-prone mice: involvement of IL-10 Blood, June 1, 2006; 107(11): 4240 - 4243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Tedgui and Z. Mallat Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways Physiol Rev, April 1, 2006; 86(2): 515 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Mercer, N. Figg, V. Stoneman, D. Braganza, and M. R. Bennett Endogenous p53 Protects Vascular Smooth Muscle Cells From Apoptosis and Reduces Atherosclerosis in ApoE Knockout Mice Circ. Res., April 1, 2005; 96(6): 667 - 674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Getz Thematic review series: The Immune System and Atherogenesis. Immune function in atherogenesis J. Lipid Res., January 1, 2005; 46(1): 1 - 10. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Teupser, S. Pavlides, M. Tan, J.-C. Gutierrez-Ramos, R. Kolbeck, and J. L. Breslow Major reduction of atherosclerosis in fractalkine (CX3CL1)-deficient mice is at the brachiocephalic artery, not the aortic root PNAS, December 21, 2004; 101(51): 17795 - 17800. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Nakai, K. Iwabuchi, S. Fujii, N. Ishimori, N. Dashtsoodol, K. Watano, T. Mishima, C. Iwabuchi, S. Tanaka, J. S. Bezbradica, et al. Natural killer T cells accelerate atherogenesis in mice Blood, October 1, 2004; 104(7): 2051 - 2059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Whitman, D. L. Rateri, S. J. Szilvassy, W. Yokoyama, and A. Daugherty Depletion of Natural Killer Cell Function Decreases Atherosclerosis in Low-Density Lipoprotein Receptor Null Mice Arterioscler. Thromb. Vasc. Biol., June 1, 2004; 24(6): 1049 - 1054. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Terme, E. Tomasello, K. Maruyama, F. Crepineau, N. Chaput, C. Flament, J.-P. Marolleau, E. Angevin, E. F. Wagner, B. Salomon, et al. IL-4 Confers NK Stimulatory Capacity to Murine Dendritic Cells: A Signaling Pathway Involving KARAP/DAP12-Triggering Receptor Expressed on Myeloid Cell 2 Molecules J. Immunol., May 15, 2004; 172(10): 5957 - 5966. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. VanderLaan, C. A. Reardon, and G. S. Getz Site Specificity of Atherosclerosis: Site-Selective Responses to Atherosclerotic Modulators Arterioscler. Thromb. Vasc. Biol., January 1, 2004; 24(1): 12 - 22. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Gojova, V. Brun, B. Esposito, F. Cottrez, P. Gourdy, P. Ardouin, A. Tedgui, Z. Mallat, and H. Groux Specific abrogation of transforming growth factor-{beta} signaling in T cells alters atherosclerotic lesion size and composition in mice Blood, December 1, 2003; 102(12): 4052 - 4058. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. J de Boer, A. E Becker, and A. C van der Wal T lymphocytes in atherogenesis--functional aspects and antigenic repertoire Cardiovasc Res, October 15, 2003; 60(1): 78 - 86. [Full Text] [PDF]
|
|
|
|
|
|
B. OSTERUD and E. BJORKLID Role of Monocytes in Atherogenesis Physiol Rev, October 1, 2003; 83(4): 1069 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Davenport and P. G. Tipping The Role of Interleukin-4 and Interleukin-12 in the Progression of Atherosclerosis in Apolipoprotein E-Deficient Mice Am. J. Pathol., September 1, 2003; 163(3): 1117 - 1125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Reardon, L. Blachowicz, J. Lukens, M. Nissenbaum, and G. S. Getz Genetic Background Selectively Influences Innominate Artery Atherosclerosis: Immune System Deficiency as a Probe Arterioscler. Thromb. Vasc. Biol., August 1, 2003; 23(8): 1449 - 1454. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Von der Thusen, J. Kuiper, T. J. C. Van Berkel, and E. A. L. Biessen Interleukins in Atherosclerosis: Molecular Pathways and Therapeutic Potential Pharmacol. Rev., March 1, 2003; 55(1): 133 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. R. Webb, M. A. Bostrom, S. J. Szilvassy, D. R. van der Westhuyzen, A. Daugherty, and F. C. de Beer Macrophage-Expressed Group IIA Secretory Phospholipase A2 Increases Atherosclerotic Lesion Formation in LDL Receptor-Deficient Mice Arterioscler. Thromb. Vasc. Biol., February 1, 2003; 23(2): 263 - 268. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Whitman, D. L. Rateri, S. J. Szilvassy, J. A. Cornicelli, and A. Daugherty Macrophage-specific expression of class A scavenger receptors in LDL receptor-/- mice decreases atherosclerosis and changes spleen morphology J. Lipid Res., August 1, 2002; 43(8): 1201 - 1208. [Abstract] [Full Text] [PDF]
|
|