Prolylcarboxypeptidase promotes angiogenesis and vascular repair

Gregory N. Adams, Evi X. Stavrou, Chao Fang, Alona Merkulova, M. Amer Alaiti, Kohsuke Nakajima, Toshifumi Morooka, Sergei Merkulov, Gretchen A. LaRusch, Daniel I. Simon, Mukesh K. Jain, Alvin H. Schmaier

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Prolylcarboxypeptidase (PRCP) is associated with leanness, hypertension, and thrombosis. PRCP-depleted mice have injured vessels with reduced Kruppel-like factor (KLF)2, KLF4, endothelial nitric oxide synthase (eNOS), and thrombomodulin. Does PRCP influence vessel growth, angiogenesis, and injury repair? PRCP depletion reduced endothelial cell growth, whereas transfection of hPRCP cDNA enhanced cell proliferation. Transfection of hPRCP cDNA, or an active site mutant (hPRCPmut) rescued reduced cell growth after PRCP siRNA knockdown. PRCP-depleted cells migrated less on scratch assay and murine PRCPgt/gt aortic segments had reduced sprouting. Matrigel plugs in PRCPgt/gt mice had reduced hemoglobin content and angiogenic capillaries by platelet endothelial cell adhesion molecule (PECAM) and NG2 immunohistochemistry. Skin wounds on PRCPgt/gt mice had delayed closure and reepithelialization with reduced PECAM staining, but increased macrophage infiltration. After limb ischemia, PRCPgt/gt mice also had reduced reperfusion of the femoral artery and angiogenesis. On femoral artery wire injury, PRCPgt/gt mice had increased neointimal formation, CD45 staining, and Ki-67 expression. Alternatively, combined PRCPgt/gt and MRP-142/2 mice were protected from wire injury with less neointimal thickening, leukocyte infiltration, and cellular proliferation. PRCP regulates cell growth, angiogenesis, and the response to vascular injury. Combined with its known roles in blood pressure and thrombosis control, PRCP is positioned as a key regulator of vascular homeostasis.

Original languageEnglish (US)
Pages (from-to)1522-1531
Number of pages10
JournalBlood
Volume122
Issue number8
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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