ACE inhibition attenuates uremia-induced aortic valve thickening in a novel mouse model

BMC Cardiovasc Disord. 2009 Mar 3:9:10. doi: 10.1186/1471-2261-9-10.

Abstract

Background: We examined whether impaired renal function causes thickening of the aortic valve leaflets in hyperlipidemic apoE-knockout (apoE-/-) mice, and whether the putative effect on the aortic valves could be prevented by inhibiting the angiotensin-converting enzyme (ACE) with enalapril.

Methods: Thickening of the aortic valve leaflets in apoE-/- mice was induced by producing mild or moderate chronic renal failure resulting from unilateral nephrectomy (1/2 NX, n = 18) or subtotal nephrectomy (5/6 NX, n = 22), respectively. Additionally, the 5/6 NX mice were randomized to no treatment (n = 8) or enalapril treatment (n = 13). The maximal thickness of each leaflet was measured from histological sections of the aortic roots.

Results: Leaflet thickness was significantly greater in the 5/6 NX mice than in the 1/2 NX mice (P = 0.030) or the unoperated mice (P = 0.003). The 5/6 NX mice treated with enalapril had significantly thinner leaflets than did the untreated 5/6 NX mice (P = 0.014).

Conclusion: Moderate uremia causes thickening of the aortic valves in apoE-/- mice, which can be attenuated by ACE inhibition. The nephrectomized apoE-/- mouse constitutes a new model for investigating the mechanisms of uremia-induced aortic valve disease, and also provides an opportunity to study its pharmacologic prevention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage*
  • Animals
  • Aortic Valve / pathology
  • Aortic Valve Stenosis / blood
  • Aortic Valve Stenosis / drug therapy*
  • Aortic Valve Stenosis / etiology
  • Aortic Valve Stenosis / physiopathology
  • Apolipoproteins E / deficiency
  • Creatinine / blood
  • Disease Models, Animal*
  • Enalapril / administration & dosage*
  • Fibrosis / drug therapy*
  • Hyperlipidemias
  • Kidney / pathology
  • Kidney / surgery
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nephrectomy
  • Renal Insufficiency / blood
  • Renal Insufficiency / complications
  • Renal Insufficiency / physiopathology
  • Renin-Angiotensin System / drug effects
  • Urea / blood
  • Uremia

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Apolipoproteins E
  • Enalapril
  • Urea
  • Creatinine