Capillary injury in the ischemic brain of hyperlipidemic, apolipoprotein B-100 transgenic mice

Zoltán Süle, Éva Mracskó, Erika Bereczki, Miklós Sántha, Tamás Csont, Péter Ferdinandy, Ferenc Bari, Eszter Farkas

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Aims: Apolipoprotein B-100 (apoB-100) has been implicated in hyperlipidemia, which contributes to the pathogenesis of vascular disorders. Our aim was to investigate whether the expression of human apoB-100 in transgenic mice and/or a high-cholesterol diet cause cerebral microvascular lesions, and whether these conditions augment ischemia-related capillary damage. Main methods: Human apoB-100 overexpressing transgenic (Tg(apoB-100), n = 23) and wild-type mice (C5/B6, Wt, n = 26) were supplied with standard or 2% cholesterol-enriched diet for 17-19 weeks. Cerebral ischemia was induced by unilateral common carotid artery occlusion. Cortical samples were embedded for electron microscopy. Microvascular density (number of microvascular profiles/examined area), lumen diameter, the swelling of astrocytic endfeet, the occurrence of endothelial microvilli (affected capillaries expressed as ratio of all capillaries encountered), and the ratio of intact capillaries (devoid of all the above pathology) were calculated. Key findings: The expression of apoB-100 coincided with decreased cortical microvascular density (195 ± 7 vs. 223 ± 8 vessels/mm2, vs. Wt; P < 0.008) and increased capillary lumen diameter (3.16 ± 0.5 vs. 2.88 ± 0.6 μm, vs. Wt; P < 0.001). Cerebral ischemia promoted the swelling of perivascular astrocytes (62.1 ± 4.2 vs. 36.5 ± 4.0%, vs. contralateral, Wt; P < 0.001), and reduced the ratio of intact capillaries (32.1 ± 5.6 vs. 65.2 ± 3.7%, vs. contralateral, Wt; P < 0.001). Hyperlipidemia did not exacerbate the injury. Significance: The overexpression of human apoB-100 alters the density of the microvascular network and the diameter of capillaries, which may compromise cerebrovascular reactivity during ischemia.

Original languageEnglish
Pages (from-to)935-939
Number of pages5
JournalLife sciences
Volume84
Issue number25-26
DOIs
Publication statusPublished - Jun 19 2009

Keywords

  • Apolipoprotein
  • Atherosclerosis
  • Brain
  • Cholesterol
  • Hyperlipidemia
  • Ischemia
  • Microvascular
  • Transgenic mouse
  • Unilateral carotid occlusion

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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