PLoS ONE (Jan 2017)

Hypercholesterolemia induced cerebral small vessel disease.

  • Peter Kraft,
  • Michael K Schuhmann,
  • Cornelia Garz,
  • Solveig Jandke,
  • Daniela Urlaub,
  • Stine Mencl,
  • Alma Zernecke,
  • Hans-Jochen Heinze,
  • Roxana O Carare,
  • Christoph Kleinschnitz,
  • Stefanie Schreiber

DOI
https://doi.org/10.1371/journal.pone.0182822
Journal volume & issue
Vol. 12, no. 8
p. e0182822

Abstract

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BackgroundWhile hypercholesterolemia plays a causative role for the development of ischemic stroke in large vessels, its significance for cerebral small vessel disease (CSVD) remains unclear. We thus aimed to understand the detailed relationship between hypercholesterolemia and CSVD using the well described Ldlr-/- mouse model.MethodsWe used Ldlr-/- mice (n = 16) and wild-type (WT) mice (n = 15) at the age of 6 and 12 months. Ldlr-/- mice develop high plasma cholesterol levels following a high fat diet. We analyzed cerebral capillaries and arterioles for intravascular erythrocyte accumulations, thrombotic vessel occlusions, blood-brain barrier (BBB) dysfunction and microbleeds.ResultsWe found a significant increase in the number of erythrocyte stases in 6 months old Ldlr-/- mice compared to all other groups (P ConclusionsIn Ldlr-/- mice, hypercholesterolemia is related to a thrombotic CSVD phenotype, which is different from hypertension-related CSVD that associates with a hemorrhagic CSVD phenotype. Our data demonstrate a relationship between hypercholesterolemia and the development of CSVD. Ldlr-/- mice appear to be an adequate animal model for research into CSVD.