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Endothelial Cell Death and Intimal Foam Cell Accumulation in the Coronary Artery of Infected Hypercholesterolemic Minipigs

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Abstract

Apoptosis of endothelial cells (ECs) has been suggested to play a role in atherosclerosis. We studied the synergism of hypercholesterolemia with Chlamydia pneumoniae and influenza virus infections on EC morphology and intimal changes in a minipig model. The coronary artery was excised at euthanasia (19 weeks of age) and serial sections were processed for the detection of EC apoptosis, histology, and transmission electron microscopy (TEM) studies. There was a significantly higher number of TUNEL-positive ECs in infected compared to noninfected groups [0.2942 % (interquartile ranges (IR), 0.2941; n = 26) versus 0 % (IR, 0; n = 12), p < 0.01]. Caspase-3 staining was negative. Cholesterol diet together with infections induced widening of the subendothelial space and appearance of increased numbers of foam cells. TEM revealed degenerative changes in cytoplasmic organelles and signs of EC necrosis. In conclusion, infection leads to an increase in coronary EC death and seems to exacerbate cholesterol-induced intimal thickening and foam cell accumulation.

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Acknowledgments

The authors wish to thank the laboratory animal technicians at the Laboratory Animal Unit, Faculty of Life Sciences, University of Copenhagen, Denmark for taking excellent care of the animals. The authors acknowledge Mrs. Liisa Lempiäinen, Mrs. Toini Tolvanen, and Mrs. Hanne Holm for the technical assistance and sectioning. We are also very grateful to Professor David J.P. Ferguson, The John Radcliffe Hospital, Oxford University, UK for the helpful discussion and comments to the TEM images. The study was financially supported by the Danish Medical Research Council (grant no. 271-06-0242), Faculty of Life Sciences (Strategic Initiative ‘BEST’), University of Copenhagen, Denmark, and Skåne University Hospital, Sweden (ALF 11617).

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Authors and Affiliations

  1. Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Ridebanevej 9, 1. Floor, 1870, Frederiksberg C, Denmark

    Malene M. Birck & Axel K. Hansen

  2. Heart Center, Turku University Hospital, Institute of Clinical Medicine, University of Turku, Turku, Finland

    Antti Saraste

  3. Department of Basic Animal and Veterinary Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Poul Hyttel

  4. Division of Pediatric Cardiology, Department of Pediatrics, Skåne University Hospital, Lund, Sweden

    Michal Odermarsky, Petru Liuba & Erkki Pesonen

  5. Department of Forensic Medicine, University of Turku, Turku, Finland

    Pekka Saukko

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  1. Malene M. Birck
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Correspondence to Malene M. Birck.

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Birck, M.M., Saraste, A., Hyttel, P. et al. Endothelial Cell Death and Intimal Foam Cell Accumulation in the Coronary Artery of Infected Hypercholesterolemic Minipigs. J. of Cardiovasc. Trans. Res. 6, 579–587 (2013). https://doi.org/10.1007/s12265-013-9463-2

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  • DOI: https://doi.org/10.1007/s12265-013-9463-2

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