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Activation of Cell Surface Bound 20S Proteasome Inhibits Vascular Cell Growth and Arteriogenesis

Wulf D Ito1, Natalie Lund2, Ziyang Zhang3

  • 1Medical Department II, Experimental Angiology, University Hospital Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany ; Department of Cardiology, University Hospital Hamburg Eppendorf, Martinistraße 52, 20246 Hamburg, Germany ; Max-Planck Institute of Heart and Lung Research, Ludwigstraße 43, 61231 Bad Nauheim, Germany ; Cardiovascular Center Oberallgaeu-Kempten, Academic Teaching Hospital, University of Ulm, Im Stillen 2, 87509 Immenstadt, Germany.

Biomed Research International
|July 7, 2015
PubMed

Insights

The extracellular 20S proteasome on vascular resident endothelial progenitor cells (VR-EPCs) influences collateral artery growth. An antibody targeting this proteasome inhibited VR-EPC proliferation and reduced collateral artery formation in vivo.

Area of Science:

  • Cardiovascular Biology
  • Cellular Proteostasis
  • Inflammation Research

Background:

  • Arteriogenesis, the formation of new collateral arteries, is an inflammatory process involving vascular resident endothelial progenitor cells (VR-EPCs).
  • Extracellular, cell surface-bound 20S proteasomes are implicated in inflammatory processes.

Purpose of the Study:

  • To investigate the role of extracellular cell surface-bound 20S proteasome in VR-EPC function and collateral artery growth.
  • To characterize a novel antibody (mAb CTA 157-2) targeting this proteasome.

Main Methods:

  • Generation of mAb CTA 157-2 against growing collateral vessel membrane fractions.
  • Mass spectrometry identification of the antibody's target as 20S proteasome subunits (α7 and β3).
  • In vitro assays assessing proteasomal activity and VR-EPC proliferation (BrdU incorporation).
  • In vivo studies involving antibody infusion into collateral circulation.

Main Results:

  • mAb CTA 157-2 specifically binds to the extracellular 20S proteasome on VR-EPCs and growing collateral vessels.
  • The antibody enhanced proteasomal activity in vitro but reduced VR-EPC proliferation.
  • In vivo, CTA 157-2 administration decreased collateral artery number, proliferation, and conductance.

Conclusions:

  • Extracellular cell surface-bound 20S proteasome plays a significant role in regulating VR-EPC function.
  • Targeting this extracellular proteasome with mAb CTA 157-2 inhibits collateral artery growth in vivo.

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