Local Mast Cell Activation Promotes Neovascularization

Cells, vol. 9, pp. 701

Abstract

Mast cells have been associated with arteriogenesis and collateral formation. In advanced human atherosclerotic plaques, mast cells have been shown to colocalize with plaque neovessels, and mast cells have also been associated with tumor vascularization. Based on these associations, we hypothesize that mast cells promote angiogenesis during ischemia. In human ischemic muscle tissue from patients with end-stage peripheral artery disease, we observed activated mast cells, predominantly located around capillaries. Also, in mouse ischemic muscles, mast cells were detected during the revascularization process and interestingly, mast cell activation status was enhanced up to 10 days after ischemia induction. To determine whether mast cells contribute to both arteriogenesis and angiogenesis, mast cells were locally activated immediately upon hind limb ischemia in C57Bl/6 mice. At day 9, we observed a 3-fold increase in activated mast cell numbers in the inguinal lymph nodes. This was accompanied by an increase in the amount of Ly6Chigh inflammatory monocytes. Interestingly, local mast cell activation increased blood flow through the hind limb (46% at day 9) compared to that in non-activated control mice. Histological analysis of the muscle tissue revealed that mast cell activation did not affect the number of collaterals, but increased the collateral diameter, as well as the number of CD31+ capillaries. Together, these data illustrate that locally activated mast cell contribute to arteriogenesis and angiogenesis.

Authors 7

1. Ilze Bot Aachen Division of BioTherapeutics, Leiden Academic Centre for Drug Research

   Leiden University

   Affiliation as printed

   Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333CC Leiden, The Netherlands

2. Daniël van der Velden Aachen Division of BioTherapeutics, Leiden Academic Centre for Drug Research

   Leiden University

   Affiliation as printed

   Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333CC Leiden, The Netherlands

3. Merel Bouwman Aachen Department of Surgery, Leiden University Medical Center Division of BioTherapeutics, Leiden Academic Centre for Drug Research Einthoven Laboratory for Experimental Vascular Medicine

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Surgery, Leiden University Medical Center, 2300RC Leiden, The Netherlands

   Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333CC Leiden, The Netherlands

   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2300RC Leiden, The Netherlands

4. Mara J. Kröner Aachen Division of BioTherapeutics, Leiden Academic Centre for Drug Research

   Leiden University

   Affiliation as printed

   Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333CC Leiden, The Netherlands

5. Johan Kuiper Aachen Division of BioTherapeutics, Leiden Academic Centre for Drug Research

   Leiden University

   Affiliation as printed

   Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, 2333CC Leiden, The Netherlands

6. Paul H.A. Quax Aachen Department of Surgery, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

   Leiden University Medical Center

   Affiliation as printed

   Department of Surgery, Leiden University Medical Center, 2300RC Leiden, The Netherlands

   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2300RC Leiden, The Netherlands

7. Margreet R. de Vries corresponding Aachen Department of Surgery, Leiden University Medical Center Einthoven Laboratory for Experimental Vascular Medicine

   Leiden University Medical Center

   Affiliation as printed

   Department of Surgery, Leiden University Medical Center, 2300RC Leiden, The Netherlands

   Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2300RC Leiden, The Netherlands