Dysregulation of HSG triggers vascular proliferative disorders

Nat Cell Biol. 2004 Sep;6(9):872-83. doi: 10.1038/ncb1161. Epub 2004 Aug 22.


Vascular proliferative disorders, such as atherosclerosis and restenosis, are the most common causes of severe cardiovascular diseases, but a common molecular mechanism remains elusive. Here, we identify and characterize a novel hyperplasia suppressor gene, named HSG (later re-named rat mitofusin-2). HSG expression was markedly reduced in hyper-proliferative vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rat arteries, balloon-injured Wistar Kyoto rat arteries, or ApoE-knockout mouse atherosclerotic arteries. Overexpression of HSG overtly suppressed serum-evoked VSMC proliferation in culture, and blocked balloon injury induced neointimal VSMC proliferation and restenosis in rat carotid arteries. The HSG anti-proliferative effect was mediated by inhibition of ERK/MAPK signalling and subsequent cell-cycle arrest. Deletion of the p21(ras) signature motif, but not the mitochondrial targeting domain, abolished HSG-induced growth arrest, indicating that rHSG-induced anti-proliferation was independent of mitochondrial fusion. Thus, rHSG functions as a cell proliferation suppressor, whereas dysregulation of rHSG results in proliferative disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arteriosclerosis / etiology
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / pathology
  • Cell Division
  • Coronary Restenosis / etiology
  • GTP Phosphohydrolases
  • Gene Expression Regulation
  • Humans
  • MAP Kinase Signaling System
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Knockout
  • Mitochondrial Proteins / biosynthesis
  • Mitochondrial Proteins / metabolism
  • Mitochondrial Proteins / physiology*
  • Molecular Sequence Data
  • Muscle, Smooth, Vascular / pathology*
  • Myocytes, Smooth Muscle / pathology
  • Oncogene Protein p21(ras) / metabolism
  • Oncogene Protein p21(ras) / physiology
  • Rats


  • Membrane Proteins
  • Mitochondrial Proteins
  • GTP Phosphohydrolases
  • Mfn2 protein, rat
  • Oncogene Protein p21(ras)

Associated data

  • GENBANK/AF036536
  • GENBANK/AF384100
  • GENBANK/U41803
  • RefSeq/NM_170060