title: Endothelial glycocalyx, apoptosis and inflammation in an atherosclerotic mouse model.
abstract: Previous experiments suggest that both increased endothelial cell apoptosis and endothelial surface glycocalyx shedding could play a role in the endothelial dysfunction and inflammation of athero-prone regions of the vasculature. We sought to elucidate the possibly synergistic mechanisms by which endothelial cell apoptosis and glycocalyx shedding promote atherogenesis.
  
  
  
  4- to 6-week old male C57Bl/6 apolipoprotein E knockout (ApoE(-/-)) mice were fed a Western diet for 10 weeks and developed plaques in their brachiocephalic arteries.
  
  
  
  Glycocalyx coverage and thickness were significantly reduced over the plaque region compared to the non-plaque region (coverage plaque: 71 ± 23%, non-plaque: 97 ± 3%, p = 0.02; thickness plaque: 0.85 ± 0.15 μm, non-plaque: 1.2 ± 0.21 μm, p = 0.006). Values in the non-plaque region were not different from those found in wild type mice fed a normal diet (coverage WT: 92 ± 3%, p = 0.7 vs. non-plaque ApoE(-/-), thickness WT: 1.1 ± 0.06 μm, p = 0.2 vs. non-plaque ApoE(-/-)). Endothelial cell apoptosis was significantly increased in ApoE(-/-) mice compared to wild type mice (ApoE(-/-):64.3 ± 33.0, WT: 1.1 ± 0.5 TUNEL-pos/cm, p = 2 × 10(-7)). The number of apoptotic endothelial cells per unit length was 2 times higher in the plaque region than in the non-plaque region of the same vessel (p = 3 × 10(-5)). Increased expression of matrix metalloproteinase 9 co-localized with glycocalyx shedding and plaque buildup.
  
  
  
  Our results suggest that, in concert with endothelial apoptosis that increases lipid permeability, glycocalyx shedding initiated by inflammation facilitates monocyte adhesion and macrophage infiltration that promote lipid retention and the development of atherosclerotic plaques.
authors.affiliation: Department of Biomedical Engineering, The City College of New York, New York, NY, USA. Electronic address: limarycancel@yahoo.com.
authors.forename: Limary M
authors.initials: LM
authors.lastname: Cancel
authors.affiliation: Department of Biomedical Engineering, The City College of New York, New York, NY, USA; Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Eno E
authors.initials: EE
authors.lastname: Ebong
authors.affiliation: Department of Biomedical Engineering, The City College of New York, New York, NY, USA.
authors.forename: Solomon
authors.initials: S
authors.lastname: Mensah
authors.affiliation: Graduate Division Summer Undergraduate Research Program, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Carly
authors.initials: C
authors.lastname: Hirschberg
authors.affiliation: Department of Biomedical Engineering, The City College of New York, New York, NY, USA. Electronic address: tarbell@ccny.cuny.edu.
authors.forename: John M
authors.initials: JM
authors.lastname: Tarbell
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D017209:Apoptosis; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001792:Blood Platelets / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D004032:Diet; D004727:Endothelium / Q000378:metabolism*; D019276:Glycocalyx / Q000378:metabolism*; D007249:Inflammation; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000074085:Mice, Knockout, ApoE; D058226:Plaque, Atherosclerotic / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002784:Cholesterol; D008055:Lipids; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D020780:Matrix Metalloproteinase 9; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C501830:Mmp9 protein, mouse
keywords: Atherosclerosis; Endothelial cell apoptosis; Glycocalyx; Inflammation