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Comprehensive gene expression profiling reveals synergistic functional networks in cerebral vessels after

Wei-Yi Ong1, Mary Pei-Ern Ng, Sau-Yeen Loke

  • 1Department of Anatomy, National University of Singapore, Singapore. wei_yi_ong@nuhs.edu.sg

Plos One
|July 23, 2013
PubMed

Insights

Hypertension and hypercholesterolemia, major stroke risk factors, induce similar gene expression changes in cerebral arteries. These overlapping molecular pathways in intracranial large artery disease may explain how combined risks worsen stroke.

Area of Science:

  • Vascular biology
  • Genomics
  • Stroke research

Background:

  • Intracranial large artery disease (ICLAD) is a significant cause of stroke, particularly in certain ethnic groups.
  • Gene expression changes in cerebral arteries affected by stroke risk factors like hypertension and hypercholesterolemia are not well understood.

Purpose of the Study:

  • To compare comprehensive gene expression profiles in the middle cerebral artery (MCA) of rabbits under hypertensive and/or hypercholesterolemic conditions.
  • To identify common and distinct molecular pathways affected by these two major stroke risk factors.

Main Methods:

  • Utilized the 2-Kidney-1-Clip method for hypertension and dietary cholesterol for hypercholesterolemia in New Zealand White rabbits.
  • Performed microarray analysis and Ingenuity Pathway Analysis on MCA tissues.
  • Verified increased hepatocyte nuclear factor 4A (HNF4A) expression in aortic tissue.

Main Results:

  • Hypertension induced up-regulation of genes in networks involving UBC, P38 MAPK, ERK, NFkB, SERPINB2, MMP1, and APP.
  • Hypercholesterolemia affected similar nodal molecules, with up-regulated common genes including UBC, SERPINB2, TNF, HNF4A, and APP.
  • Despite low gene overlap, both conditions impacted related molecular pathways, suggesting a shared mechanism in cerebral artery disease.

Conclusions:

  • Hypertension and hypercholesterolemia trigger overlapping gene expression patterns in cerebral arteries.
  • These shared molecular pathways may contribute to the synergistic effect of risk factors in the pathogenesis of ICLAD.
  • Understanding these pathways offers potential targets for stroke prevention and treatment.

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