PMID- 19275472 OWN - NLM STAT- MEDLINE DCOM- 20091027 LR - 20220316 IS - 1937-335X (Electronic) IS - 1937-3341 (Linking) VI - 15 IP - 9 DP - 2009 Sep TI - B-type natriuretic peptide enhances vasculogenesis by promoting number and functional properties of early endothelial progenitor cells. PG - 2741-9 LID - 10.1089/ten.TEA.2008.0414 [doi] AB - OBJECTIVE: To test the hypothesis that B-type natriuretic peptide (BNP) acts as a potent vasculogenic agent by enhancing the number, proliferation, adhesion, and migration of endothelial progenitor cells (EPCs). BACKGROUND: BNP is a neurohormonal peptide that predicts outcome and used for treatment in chronic heart failure patients. It has been shown to promote angiogenesis in experimental animals. EPCs have been demonstrated to contribute to postnatal angiogenesis and vasculogenesis. METHODS: The number of EPC colony forming units (CFU) and levels of N-terminal ProBNP were assayed in patients with severe, yet controlled, New York Heart Association (NYHA) II-IV heart failure. The in vitro effects of BNP on early EPC-CFU numbers, proliferation, migration, adhesive, and vascular tube formation capacities were studied using human and murine systems. The effects of in vivo BNP administration on Sca-1/Flk-1 progenitors and on vasculogenesis in the hindlimb ischemia model were then assayed in wild-type mice. RESULTS: A significant correlation was found between circulating N-terminal ProBNP levels and EPC-CFU numbers. We observed a dose-dependent effect of BNP on the numbers of CFU and proliferation capacity of human EPCs as well as on their adhesive, migratory, and tube formation properties, in vitro. Systemic BNP administration to mice led to a significant increase in bone marrow Sca-1/Flk-1 EPCs and improvement in blood flow and capillary density in the ischemic limbs of mice. CONCLUSIONS: BNP promotes vessel growth by increasing the number of endothelial progenitors and enhancing their functional properties. These provasculogenic properties of BNP could account for some of its beneficial effects in chronic heart failure patients and may be harnessed for the purpose of improving collateral formation in ischemic subjects. FAU - Shmilovich, Haim AU - Shmilovich H AD - Department of Cardiology, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Ben-Shoshan, Jeremy AU - Ben-Shoshan J FAU - Tal, Reshef AU - Tal R FAU - Afek, Arnon AU - Afek A FAU - Barshack, Iris AU - Barshack I FAU - Maysel-Auslander, Sofia AU - Maysel-Auslander S FAU - Harats, Dror AU - Harats D FAU - Keren, Gad AU - Keren G FAU - George, Jacob AU - George J LA - eng PT - Journal Article PL - United States TA - Tissue Eng Part A JT - Tissue engineering. Part A JID - 101466659 RN - 0 (ATXN1 protein, human) RN - 0 (Ataxin-1) RN - 0 (Ataxins) RN - 0 (Atxn1 protein, mouse) RN - 0 (Drug Combinations) RN - 0 (Laminin) RN - 0 (Nerve Tissue Proteins) RN - 0 (Nuclear Proteins) RN - 0 (Peptide Fragments) RN - 0 (Proteoglycans) RN - 0 (pro-brain natriuretic peptide (1-76)) RN - 114471-18-0 (Natriuretic Peptide, Brain) RN - 119978-18-6 (matrigel) RN - 9007-34-5 (Collagen) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1) SB - IM MH - Animals MH - Ataxin-1 MH - Ataxins MH - Bone Marrow Cells/cytology/drug effects MH - Cell Adhesion/drug effects MH - Cell Count MH - Cell Movement/drug effects MH - Collagen/metabolism MH - Colony-Forming Units Assay MH - Drug Combinations MH - Endothelial Cells/*cytology/drug effects/enzymology MH - Heart Failure/blood MH - Humans MH - Ischemia MH - Laminin/metabolism MH - Mice MH - Natriuretic Peptide, Brain/administration & dosage/blood/*metabolism/pharmacology MH - Neovascularization, Pathologic/metabolism MH - *Neovascularization, Physiologic/drug effects MH - Nerve Tissue Proteins/metabolism MH - Nuclear Proteins/metabolism MH - Peptide Fragments/blood MH - Phosphatidylinositol 3-Kinases/metabolism MH - Proteoglycans/metabolism MH - Stem Cells/*cytology/drug effects/enzymology MH - Vascular Endothelial Growth Factor Receptor-1/metabolism EDAT- 2009/03/12 09:00 MHDA- 2009/10/29 06:00 CRDT- 2009/03/12 09:00 PHST- 2009/03/12 09:00 [entrez] PHST- 2009/03/12 09:00 [pubmed] PHST- 2009/10/29 06:00 [medline] AID - 10.1089/ten.TEA.2008.0414 [doi] PST - ppublish SO - Tissue Eng Part A. 2009 Sep;15(9):2741-9. doi: 10.1089/ten.TEA.2008.0414.