Prolylcarboxypeptidase promotes angiogenesis and vascular repair.

Pubmed ID: 23744584

Pubmed Central ID: PMC3750346

Journal: Blood

Publication Date: Aug. 22, 2013

Affiliation: Department of Medicine, Hematology and Oncology Division, Case WesternReserve University and University Hospitals Case Medical Center, Cleveland, OH 44106, USA.

MeSH Terms: Humans, Cell Proliferation, Cells, Cultured, Animals, Endothelial Cells, Mice, Cell Movement, Ischemia, Neovascularization, Physiologic, Human Umbilical Vein Endothelial Cells, Neovascularization, Pathologic, Mice, Inbred C57BL, Carboxypeptidases, Aorta, Apoptosis, Calgranulin B, Cattle, Femoral Artery, Ki-67 Antigen, Wound Healing, Platelet Endothelial Cell Adhesion Molecule-1, Kruppel-Like Factor 4

Grants: HL112666, R21 HL112666, HL076754, HL097593, HL110630, HL57506, HL85816, R01 HL097593, R01 HL110630, R37 HL057506, R01 HL052779, HL052779-16, HL088548, HL112486, T32 HL105338, R01 HL085816, R01 HL076754, R01 HL112486, R01 HL088548, R01 HL057506

Authors: Fang C, Adams GN, Schmaier AH, Larusch GA, Merkulova A, Simon DI, Jain MK, Stavrou EX, Alaiti MA, Nakajima K, Morooka T, Merkulov S

Cite As: Adams GN, Stavrou EX, Fang C, Merkulova A, Alaiti MA, Nakajima K, Morooka T, Merkulov S, Larusch GA, Simon DI, Jain MK, Schmaier AH. Prolylcarboxypeptidase promotes angiogenesis and vascular repair. Blood 2013 Aug 22;122(8):1522-31. Epub 2013 Jun 6.

Studies:

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 PRCP(gt/gt) aortic segments had reduced sprouting. Matrigel plugs in PRCP(gt/gt) mice had reduced hemoglobin content and angiogenic capillaries by platelet endothelial cell adhesion molecule (PECAM) and NG2 immunohistochemistry. Skin wounds on PRCP(gt/gt) mice had delayed closure and reepithelialization with reduced PECAM staining, but increased macrophage infiltration. After limb ischemia, PRCP(gt/gt) mice also had reduced reperfusion of the femoral artery and angiogenesis. On femoral artery wire injury, PRCP(gt/gt) mice had increased neointimal formation, CD45 staining, and Ki-67 expression. Alternatively, combined PRCP(gt/gt) and MRP-14(-/-) 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.