title: Physiological concentration of atrial natriuretic peptide induces endothelial regeneration in vitro.
abstract: Both nitric oxide (NO) and natriuretic peptides produce apoptosis of vascular smooth muscle cells. However, there is evidence that NO induces endothelial cell proliferation, which suggests that there is a difference in the response of endothelial cells to natriuretic peptides. The purpose of this study was to investigate the effect of atrial natriuretic peptide (ANP) on human endothelial cell survival. ANP within the physiological concentration (10(-11) mol/l) induced a 52% increase in the number of human coronary arterial endothelial cells and a 63% increase in human umbilical vein endothelial cells at a low concentration of serum. The increase in cell numbers was blocked by pretreatment with RP8-CPT-cGMP (RP8), a cGMP-dependent protein kinase inhibitor, with wortmannin, an Akt/PKB inhibitor, and with PD-98059, an ERK1/2 inhibitor. In a Transwell migration test, ANP also increased the cell migration, and RP8, wortmannin, and PD-98059 blocked this increase. A wound healing assay was performed to examine the effects of ANP on regeneration in vitro. ANP increased both cell numbers and migration, but the effects were blocked by the above three kinase inhibitors. ANP increased the expression of phospho-Akt and of phospho-ERK1/2 within 1.5 h. These results suggest that ANP can potentiate endothelial regeneration by cGMP-dependent protein kinase stimulation and subsequent Akt and ERK1/2 activations.
authors.affiliation: Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Kook
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
authors.forename: Bong Seok
authors.initials: BS
authors.lastname: Choi
authors.forename: Naoki
authors.initials: N
authors.lastname: Sawada
authors.forename: Kentaro
authors.initials: K
authors.lastname: Doi
authors.forename: Tae Ju
authors.initials: TJ
authors.lastname: Hwang
authors.forename: Kyung Keun
authors.initials: KK
authors.lastname: Kim
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arai
authors.forename: Yung Hong
authors.initials: YH
authors.lastname: Baik
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000199:Actins / Q000032:analysis; D000730:Androstadienes / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage* / Q000502:physiology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D012038:Regeneration; D013873:Thionucleotides / Q000494:pharmacology; D014471:Umbilical Veins; D000077191:Wortmannin; D014945:Wound Healing
chemical_list: C090860:8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphorothioate; D000199:Actins; D000730:Androstadienes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D011518:Proto-Oncogene Proteins; D013873:Thionucleotides; D009320:Atrial Natriuretic Factor; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D017869:Cyclic GMP-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D006152:Cyclic GMP; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin