Up-regulation of a hydrogen peroxide-responsive pre-mRNA binding protein in atherosclerosis and intimal hyperplasia

Cardiovasc Pathol. May-Jun 2009;18(3):167-72. doi: 10.1016/j.carpath.2008.03.008. Epub 2008 May 27.

Abstract

Background: Multiple lines of investigation have implicated hydrogen peroxide (H(2)O(2)) as an important endogenous mediator of cell proliferation in the vessel wall. Heterogeneous nuclear ribonucleoprotein C (hnRNP-C), a nuclear pre-mRNA binding protein that plays roles in vertebrate cell proliferation and differentiation, has been identified as a component of a vascular cell signaling pathway activated by low physiologic levels of H(2)O(2). The expression of hnRNP-C in human arteries has not previously been assessed.

Methods: Segments of human proximal internal carotid arteries were evaluated for the expression of hnRNP-C by immunohistochemistry.

Results: In normal proximal internal carotid arteries, hnRNP-C is expressed predominantly by the endothelium, with significantly lower expression by medial smooth muscle. In preatherosclerotic intimal hyperplasia, hnRNP-C is up-regulated in the artery wall, due to the robust expression by the intimal smooth muscle cells, without up-regulation in the medial smooth muscle cells. In arteries with atherosclerotic lesions, there is strong expression of hnRNP-C not only by intimal cells but also by medial smooth muscle cells.

Conclusions: The H(2)O(2) responsive pre-mRNA binding protein hnRNP-C is up-regulated in atherosclerosis and in preatherosclerotic intimal hyperplasia in humans, supporting the hypothesis that H(2)O(2) is a regulator of vascular cell proliferation in these conditions. These data also suggest that hnRNP-C may be useful as a marker of vascular cell activation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autopsy
  • Biomarkers / analysis
  • Carotid Artery Diseases / metabolism*
  • Carotid Artery Diseases / pathology
  • Carotid Artery, Internal / chemistry*
  • Carotid Artery, Internal / pathology
  • Endothelium, Vascular / chemistry
  • Heterogeneous-Nuclear Ribonucleoprotein Group C / analysis*
  • Humans
  • Hydrogen Peroxide / metabolism*
  • Hyperplasia
  • Immunohistochemistry
  • Middle Aged
  • Muscle, Smooth, Vascular / chemistry
  • Tunica Intima / chemistry*
  • Tunica Intima / pathology
  • Up-Regulation

Substances

  • Biomarkers
  • Heterogeneous-Nuclear Ribonucleoprotein Group C
  • Hydrogen Peroxide