Download PDF
Thromb Haemost 2001; 85(05): 908-914
DOI: 10.1055/s-0037-1615767
Review Article
Schattauer GmbH

Increased ICAM-1 and PECAM-1 Transcription Levels in the Heart of Apo-E Deficient Mice in Comparison to Wild Type (C57BL6).

Kazem Zibara
1   Thrombosis Research Institute, London, UK
,
Kamel Chettab
2   INSERM U331/Faculté de Médecine RTH Laënnec, Lyon, France
,
Brigitte McGregor
2   INSERM U331/Faculté de Médecine RTH Laënnec, Lyon, France
,
Robin Poston
3   Department of Experimental Pathology, UMDS, Guy‘s Hospital, London, UK
,
John McGregor
2   INSERM U331/Faculté de Médecine RTH Laënnec, Lyon, France
› Author Affiliations
Further Information

Publication History

Received 26 June 2001

Accepted after resubmission 14 December 2000

Publication Date:
11 December 2017 (online)

    Permissions and Reprints

Summary

Adhesion molecules and chemoattractants are thought to play a critical role in the homing of leukocytes to sites of vascular lesions. Apo-E deficiency in mice creates an atherosclerotic model that mimics vascular lesions in man. Little is known on the effect of Apo-E deficiency on expression of adhesion molecules in the hearts of these animals. In this study, male C57BL6 and Apo-E deficient mice were fed a chow diet over periods of time (0 to 20 weeks). The transcription levels of major adhesion molecules (ICAM-1, PECAM-1), present in the heart, were followed by northern blots. Immunohistochemistry was used to localize these adhesion molecules in the heart. Results show a significant increase in gene transcription levels of ICAM-1 and PECAM-1 in Apo-E animals, but not wild type, at 16 and 20 weeks of chow diet. Such increase in levels of transcription was not observed in younger Apo-E and C57BL6 animals (0, 6 weeks of diet). ICAM-1 and PECAM-1 were strongly expressed in the endocardium and heart microvessels. In contrast, VCAM-1 was poorly stained, with only an occasional expression on the endocardium and arterioles. Enhanced gene expression levels of heart ICAM-1 and PECAM-1 observed in Apo-E deficient mice, but not in control animals, appears to induce the initial stages of an inflammatory reaction. Such observations, not previously reported, may induce heart vascular remodeling.

Keywords

Atherosclerosis - adhesion molecules - apolipoprotein E - knockout mice - heart - northern
 

  • References

  • 1 Ross R. The pathogenesis of atherosclerosis. Nature 1993; 362: 801-9.
    CrossrefPubMedGoogle Scholar
  • 2 Suzuki H, Kuriara Y, Takeya M, Kamada N, Kataoka M, Jishage K, Ueda O, Sagakuchi H, Higashi T, Suzuki T, Takashima Y, Kawabe Y, Cynnshi O, Wada Y, Honda M, Kuriara H, Aburatani H, Doi T, Matsumoto A, Azuma S, Noda T, Toyoda Y, Itakura H, Yazaki Y, Horiuchi S, Takahashi K, Kruijt JK, Berkel TJC, Steinbrecher UP, Ishibashi S, Maeda N, Gordon S, Kodama T. A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature 1997; 386: 292-6.
    CrossrefPubMedGoogle Scholar
  • 3 Hajjar DP, Nicholson AC. Atherosclerosis. American Scientist 1995; 83: 460-7.
    PubMedGoogle Scholar
  • 4 Munro JM, Cotran RS. Biology of the disease. The pathogenesis of atherosclerosis. Atherogenesis and inflammation. Lab Invest 1988; 58: 249-61.
    PubMedGoogle Scholar
  • 5 Ohno T, Gordon D, San H, Pompili VJ, Imperiale MJ, Nabel GJ, Nabel EG. Gene therapy for vascular smooth muscle cell proliferation after arterial injury. Science 1994; 265: 781-4.
    CrossrefPubMedGoogle Scholar
  • 6 Springer TA. Adhesion receptors of the immune system. Nature 1990; 346: 425-34.
    CrossrefPubMedGoogle Scholar
  • 7 Poston RN, Haskard DO, Coucher JR, Gall NP, Johnson-Tidey RR. Expression of intercellular adhesion molecule-1 in atherosclerotic plaques. Am J Pathol 1992; 140: 665-73.
    PubMedGoogle Scholar
  • 8 Bogen S, Pak J, Garifallou M, Deng X, Muller WA. Monoclonal antibody to murine PECAM-1 (CD31) blocks acute inflammation in vivo. J Exp Med 1994; 179: 1059-64.
    CrossrefPubMedGoogle Scholar
  • 9 Cybulsky MI, Gimbrone Jr MA. Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science 1991; 251: 788-91.
    CrossrefPubMedGoogle Scholar
  • 10 Johnson-Tidey RR, McGregor JL, Taylor PR, Poston RN. Increase in the adhesion molecule P-selectin in endothelium overlaying atherosclerotic plaques: coexpression with intercellular adhesion molecule-1. Am J Pathol 1994; 144: 952-61.
    PubMedGoogle Scholar
  • 11 Schaefer EJ, Gregg RE, Ghiselli G, Forte TM, Ordovas JM, Zech LA, Brewer Jr HB. Familial apolipoprotein deficiency. J Clin Invest 1986; 78: 1206-19.
    CrossrefPubMedGoogle Scholar
  • 12 Piedrahita JA, Zhang SH, Hagaman JR, Oliver PM, Maeda N. Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells. Proc Natl Acad Sci USA 1992; 89: 4471-5.
    CrossrefPubMedGoogle Scholar
  • 13 Reddick RL, Zhang SH, Maeda N. Atherosclerosis in mice lacking Apo E: Evaluation of lesional development and progression. Arterioscler Thromb 1994; 14: 141-7.
    CrossrefPubMedGoogle Scholar
  • 14 Nakashima Y, Plump AS, Raines EW, Breslow JL, Ross R. ApoE-deficient mice develop lesions of all phases of atherosclerosis troughout the arterial tree. Arterioscler Thromb 1994; 14: 133-40.
    CrossrefPubMedGoogle Scholar
  • 15 Davies MJ, Woolf N, Rowles PM, Pepper J. Morphology of the endothelium over atherosclerotic plaques in human coronary arteries. Br Heart J 1988; 60: 459-64.
    CrossrefPubMedGoogle Scholar
  • 16 Rosenfeld ME, Tsukada T, Gown AM, Ross R. Fatty streak initiation in a Watanabe heritable hyperlipemic and comparably hypercholesterolemic fat-fed rabbits. Arteriosclerosis 1987; 7: 9-23.
    CrossrefPubMedGoogle Scholar
  • 17 Shih DM, Welch C, Lusis AJ. New insights into atherosclerosis from studies with mouse models. Mol Med Today 1995; 1: 364-72.
    CrossrefPubMedGoogle Scholar
  • 18 Stary HC, Chandler AB, Dinsmore RE, Fuster V, Glagov S, Insull Jr W, Rosenfeld ME, Schwartz CJ, Wagner WD, Wissler RW. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. Circulation 1995; 92: 1355-74.
    CrossrefPubMedGoogle Scholar
  • 19 Chomczynski P, Sacchi N. Single step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987; 162: 156-9.
    PubMedGoogle Scholar
  • 20 Sambrook J, Fritsch EF, Maniatis T. Molecular Cloning: A Laboratory Manuel. 1989. 2nd Ed. Cold Spring Harbor Laboratory; Cold Spring Harbor, NY.:
    Google Scholar
  • 21 Wahle E, Keller W. The biochemistry of 3′-end cleavage and polyadenylation of messenger RNA precursors. Annu Rev Biochem. 1992; 61: 419-40.
    CrossrefPubMedGoogle Scholar
  • 22 Onrust SV, Hartl PM, Rosen SD, Hanahan D. Modulation of L-selectin ligand expression during an immune response accompanying tumorigenesis in transgenic mice. J Clin Invest 1996; 97: 54-64.
    CrossrefPubMedGoogle Scholar
  • 23 Zibara K, Chignier E, Covacho C, Poston R, Canard G, Hardy P, and McGregor JL. Modulation of the Expression of Endothelial ICAM-1, PECAM-1, and VCAM-1 in Aortic Arch Lesions of Apo-E Deficient Mice Compared to Wild Type. Arteriosclerosis, Thrombosis and Vascular Biology 2000; 20: 2288-96.
    CrossrefPubMedGoogle Scholar
  • 24 Shih DM, Welch C, and Lusis AJ. New insights into atherosclerosis from studies with mouse models. Molecular Medicine Today, 1995; 1: 364-73.
    CrossrefPubMedGoogle Scholar
  • 25 Kume N, Cybulsky MI, Gimbrone Jr MA. Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells. J Clin Invest 1992; 90: 1138-44.
    CrossrefPubMedGoogle Scholar
  • 26 Topper JN, Gimbrone Jr MA. Blood flow and vascular gene expression: fluid shear stress as a modulator of endothelial phenotype. Mol Med Today, 1999; 5: 40-6.
    CrossrefPubMedGoogle Scholar
  • 27 Bourdillon MC, Poston R, Covacho C, Chignier E, Bricca G, McGregor JL. ICAM-1 deficiency reduces atherosclerotic lesions in double knockout mice (Apo-E–/–/ICAM-1–/–) fed a fat or a chow diet. Arteriosclerosis, Thrombosis and Vascular Biology. 2000 in press.
    PubMedGoogle Scholar
  • 28 Patel SS, Thiagarajan R, Wilerson JT, Yeh ET. Inhibition of alpha4 integrin and ICAM-1 markedly attenuate macrophage homing to atherosclerotic plaques in ApoE-deficient mice. Circulation 1998; 97 (Suppl. 01) 75-81.
    CrossrefPubMedGoogle Scholar
  • 29 Gu L, Okada Y, Clinton SK, Gerard C, Sukhova GK, Libby P, Rollins BJ. Absence of monocyte chemoattractant protein-1 reduces atherosclerotic in low-density lipoprotein receptor-deficient mice. Mol Cell 1998; 2: 275-81.
    CrossrefPubMedGoogle Scholar
  • 30 Boring L, Gosling J, Cleary M, Charo IF. Decreased lesion formation in CCR2–/– mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 1998; 394: 894-7.
    CrossrefPubMedGoogle Scholar
  • 31 Gawaz M, Neuman FJ, Dickfeld T, Koch W, Laugwitz KL, Adelsberger H, Langenbrink K, Page S, Neumeier D, Schömig A, Brand K. Activated platelets induce monocyte chemotactic protein-1 secretion and surface expression of intercellular adhesion molecule-1 on endothelial cells. Circulation 1998; 98: 1151-2.
    CrossrefPubMedGoogle Scholar
  • 32 Vaporcyian AA, DeLisser HM, Yan H, Mendiguren II, Thom SR, Jones PA, Ward PA, Albelda SM. Involvement of platelet endothelial cell adhesion molecule-1 in neutrophil recruitment in vivo. Science (Wash DC) 1993; 262: 1580-2.
    CrossrefPubMedGoogle Scholar
  • 33 Albelda SM, Muller WA, Buck CA, Newman PJ. Molecular and cellular properties of PECAM-1 (endoCam/CD 31): a novel vascular cell-cell adhesion molecule. J Cell Biol 1991; 114: 1059-68.
    CrossrefPubMedGoogle Scholar
  • 34 Piali L, Hammel P, Uherek C, Bachmann F, Gisler RH, Dunon D, Imhof BA. CD31/PECAM-1 is a ligand for avb3 integrin involved in adhesion of leukocytes to endothelium. J Cell Biol 1995; 130: 451-60.
    CrossrefPubMedGoogle Scholar
  • 35 Buckley CD, Doyonnas R, Newton JP, Blystone SD, Brown EJ, Watt SM, Simmons DL. Identification of avb3 as a heterotopic ligand for CD31/ PECAM-1. J Cell Sci 1996; 109: 437-45.
    PubMedGoogle Scholar
  • 36 Rival Y, Del Maschio A, Rabiet MJ, Dejana E, and Duperray A. Inhibition of platelet endothelial cell adhesion molecule-1 synthesis and leukocyte transmigraion in endothelial cells by the combined action of TNF- and IFN- . J Immunol 1996; 157: 1233-41.
    PubMedGoogle Scholar
  • 37 Elices MJ, Osborn L, Takada Y, Crouse C, Luhowskyl S, Hemler ME, Lobb RR. VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-fibrinogen binding site. Cell 1990; 60: 577-84.
    CrossrefPubMedGoogle Scholar
  • 38 Cybulsky MI, Gimbrone MA. Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science 1991; 251: 788-91.
    CrossrefPubMedGoogle Scholar
  • 39 Carlos TM, Harlan JM. Leukocyte-endothelial adhesion molecules. Blood 1994; 84: 2068-2101.
    PubMedGoogle Scholar
  • 40 Russell PS, Chase CM, Colvin RB. Coronary atherosclerosis in transplanted mouse hearts: effects of treatment with monoclonal antibodies to intercellular adhesion molecule-1 and leukocyte function-associated antigen-1. Transplantation, 1995; 60 (Suppl. 07) 724-9.
    CrossrefPubMedGoogle Scholar
  • 41 Patten RD, Aronovitz MJ, Deras Mejia L, Pandian NG, Hanak G, Smith JJ, Mendelsohn ME, Konstam MA. Ventricular remodeling in a mouse model of myocardial infarction. Am J Physiol 1998; 274 (Suppl. 05) H1812-20.
    PubMedGoogle Scholar
  • 42 Yang R, Powell Braxton L, Ogaoawara AK, Dybdal N, Bunting S, Ohneda O, Jin H. Hypertension and endothelial dysfunction in apolipoprotein E knockout mice. Arteriosclerosis, Thrombosis and Vascular Biology, 1999; 19 (Suppl. 11) 2762-8.
    CrossrefPubMedGoogle Scholar