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miRNA for Atherosclerosis and Angiogenesis

Scientists at the Leiden University Medical Center (LUMC) have found miRNA that play a role in vascular remodelling, reducing atherosclerotic plaques while stimulating therapeutic angiogenesis.

An important problem with therapeutic neovascularization is that stimulation of positive vascular remodelling such as angiogenesis and arteriogenesis often also stimulate negative vascular remodelling such as atherosclerosis and restenosis. This Janus phenomenon causes obvious problems when developing treatments to stimulate neovascularization in patents with occlusive arterial disease.

Researchers at the LUMC have found that inhibition of a particular microRNA gene cluster plays a role in vascular remodelling.  Inhibitors of select miRNA were tested in vivo in mice on a high fat diet and were demonstrated to reduce atherosclerosis and restenosis with a 50% reduction in plaque size. The inhibitors were also found to greatly stabilize the plaque phenotype since there was a 50% or more decrease in necrotic core formation in the plaque, decrease macrophage content in plaques, and decrease plasma total cholesterol. At the same time, inhibition of these miRNA was unexpectedly found to increase therapeutic angiogenesis as demonstrated in a mouse hind limb ischemia model. 

These data indicate a potentially novel regulatory pathway and new target for ischemic cardiovascular disease.  Inhibition of these miRNA’s would, for the first time, provide the opportunity to inhibit atherosclerosis and restenosis while simultaneously stimulating therapeutic neovascularization. 

Using cultures of smooth muscle cells, endothelial cells, fibroblasts, bone marrow derived mast cells and macrophages, they were able to confirm direct regulation of multiple anti-atherogenic target genes by microRNAs.

We are currently looking for collaborators or licensees to further develop this invention.

Key benefits

Inhibition of miRNA leads to:

  • Reduction in plaque size
  • Decrease necrotic core formation in plaques
  • Decrease macrophage content in plaques
  • Decrease plasma total cholesterol
  • Stimulation of therapeutic angiogenesis

Applications

  • Development of therapeutic agent to prevent or treat atherosclerotic plaques while increasing angiogenesis
  • Exploration of miRNA downstream targets

Development stage

  • Inhibitors of miRNA have been tested in vivo
  • Direct regulation of multiple anti-atherogenic target genes has been found

Luris reference number

INV-060.025

Patent status

A patent application has been filed

Further information

Rob Mayfield Director Knowledge Partnering +31-71-527 2522 +31-6-1475 2489 r.h.mayfield@luris.nl Room number: 1.10