Deletion of the FHL2 gene attenuates the formation of atherosclerotic lesions after a cholesterol-enriched diet

Life Sci. 2010 Feb 27;86(9-10):365-71. doi: 10.1016/j.lfs.2010.01.007. Epub 2010 Jan 21.

Abstract

Aims: FHL2, a member of the four and a half LIM domain (FHL) family of proteins, may play an important role in the circulatory system and in particular atherosclerosis.

Main methods: To investigate the role of FHL2 in atherogenesis, FHL2-null and wild-type control male mice were fed either a normal chow (NC) or a cholesterol-enriched diet (CED).

Key findings: At 3 months post CED, aortic atherosclerotic plaques were observed in both control and FHL2-null mice. Lesions in control mice increased dramatically by 6 months of CED. In contrast, lesion size did not increase during this time in CED-fed FHL2-null mice. Relative to control mice on a normal chow of diet (NCD), control mice on a CED exhibited lower circulating nitric oxide (NO) levels, and decreased expression of connexin37 (Cx37) and Cx40 in aortic endothelium. In contrast, FHL2-null mice on a CED maintained similar levels of circulating NO as FHL2-null mice fed a NCD. Cxs levels in aortic endothelium of FHL2-null mutants on a NCD were lower relative to control mice on a NCD, and did not decrease with CED.

Significance: Our data demonstrate a role for FHL2 in atherogenesis, the regulation of circular NO release, and expression of gap junctions within aortic endothelium.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / metabolism
  • Atherosclerosis / genetics*
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology*
  • Cholesterol, Dietary / adverse effects*
  • Connexins / biosynthesis
  • Connexins / metabolism
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Gene Deletion*
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / physiology
  • LIM-Homeodomain Proteins
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle Proteins / deficiency*
  • Muscle Proteins / genetics*
  • Muscle Proteins / physiology
  • Nitric Oxide / metabolism
  • Transcription Factors / deficiency*
  • Transcription Factors / genetics*
  • Transcription Factors / physiology

Substances

  • Cholesterol, Dietary
  • Connexins
  • Fhl2 protein, mouse
  • Homeodomain Proteins
  • LIM-Homeodomain Proteins
  • Muscle Proteins
  • Transcription Factors
  • Nitric Oxide