Cardiac ankyrin repeat protein (CARP) expression in human and murine atherosclerotic lesions: activin induces CARP in smooth muscle cells

Arterioscler Thromb Vasc Biol. 2003 Jan 1;23(1):64-8. doi: 10.1161/01.atv.0000042218.13101.50.

Abstract

Objective: Cardiac ankyrin repeat protein (CARP) is a transcription factor-related protein that has been studied most extensively in the heart. In the present study, we investigated the expression and the potential function of CARP in human and murine atherosclerosis.

Methods and results: CARP expression was observed by in situ hybridization in endothelial cells lining human atherosclerotic plaques, whereas lesion macrophages were devoid of CARP. Furthermore, we established that CARP mRNA and smooth muscle (SM) alpha-actin antigen both colocalized in a subset of intimal smooth muscle cells (SMCs), whereas no CARP mRNA was encountered in quiescent SMCs in the media. The CARP mRNA-expressing intimal SMCs were distinct from intimal SMCs that synthesized the activation marker osteopontin or proliferating cell nuclear antigen. In addition, we showed that activin A, a member of the TGFbeta superfamily that prevents SMC-rich lesion formation, induced CARP mRNA expression in cultured SMCs.

Conclusions: Based on our data and the knowledge that CARP reduces the proliferation of cultured SMCs, we propose that CARP is involved in inhibition of vascular lesion formation.

MeSH terms

  • Activins / physiology*
  • Adult
  • Aged
  • Animals
  • Ankyrin Repeat / physiology
  • Arteriosclerosis / metabolism*
  • Arteriosclerosis / pathology*
  • Arteriosclerosis / prevention & control
  • Cell Division / physiology
  • Cells, Cultured
  • Coronary Restenosis / metabolism
  • Coronary Restenosis / pathology
  • Endothelium, Vascular / chemistry
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Female
  • Humans
  • Iliac Artery / chemistry
  • Iliac Artery / metabolism
  • Iliac Artery / pathology
  • Inhibin-beta Subunits / physiology*
  • Macrophages / chemistry
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Middle Aged
  • Muscle Proteins / biosynthesis
  • Muscle Proteins / physiology
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / pathology
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / physiology*
  • RNA, Messenger / biosynthesis
  • Repressor Proteins / biosynthesis*
  • Repressor Proteins / physiology*
  • Saphenous Vein / chemistry
  • Saphenous Vein / metabolism
  • Saphenous Vein / pathology

Substances

  • ANKRD1 protein, human
  • Ankrd1 protein, mouse
  • Muscle Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • Repressor Proteins
  • activin A
  • Activins
  • Inhibin-beta Subunits