Regulatory role for nucleosome assembly protein-1 in the proliferative and vasculogenic phenotype of pulmonary endothelium

• Published in: American journal of physiology. Lung cellular and molecular physiology 2008-03, Vol.294 (3), p.L431-L439
• Main Authors: Clark, Jennifer, Alvarez, Diego F, Alexeyev, Mikhail, King, Judy A. C, Huang, Lan, Yoder, Mervin C, Stevens, Troy
• Format: Article
• Language: English
• Subjects: Animals; Blood vessels; Cell Cycle Proteins - physiology; Cell growth; Cell Proliferation - drug effects; Cells; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Gene expression; Griffonia simplicifolia; Helix pomatia; Lungs; Microcirculation - cytology; Microcirculation - physiology; Neovascularization, Physiologic - physiology; Nuclear Proteins - physiology; Nucleosome Assembly Protein 1; Phenotype; Proteins
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00316.2007

Departments of 1 Pharmacology, 2 Cell Biology and Neuroscience, and 3 Pathology, 4 Center for Lung Biology, University of South Alabama College of Medicine, Mobile, Alabama; and Departments of 5 Biochemistry and Molecular Biology and 6 Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana Submitted 6 August 2007 ; accepted in final form 31 October 2007 Pulmonary microvascular endothelial cells (PMVECs) are enriched with progenitor cells that underlie their rapid proliferation and vasculogenic capacity. However, the molecular basis for such an enhanced growth potential is unknown. Nucleosome assembly protein-1 (NAP1), and its related family of proteins, have been incriminated in control of cell growth in a range of species. We therefore sought to determine whether NAP1 contributes to the rapid proliferation and vasculogenesis that is observed in PMVECs. NAP1 was expressed at a high level in two fast-growing cell types, including PMVECs and resident microvascular endothelial progenitor cells that were selected from PMVECs, whereas it was expressed at a low level in slow-growing pulmonary artery endothelial cells (PAECs). Heterologous NAP1 expression increased the growth potential of PAECs, whereas inhibiting NAP1 expression reduced the growth potential of PMVECs. Despite its impact on endothelial cell growth, NAP1 did not influence the expression of endothelial cell-selective markers (PECAM-1, VE-cadherin, von Willebrand factor), and it did not influence cell type-specific lectin binding criterion; PMVECs interact with Griffonia simplicifolia lectin, whereas PAECs interact with Helix pomatia lectin. PMVECs possess a higher basal transelectrical resistance than do PAECs, indicative of their more restrictive barrier property. Changing NAP1 expression did not normalize this basal barrier function between PMVECs and PAECs. To examine whether the growth-promoting actions of NAP1 influence blood vessel formation, endothelial cells were mixed into Matrigel and subcutaneously implanted. PMVECs generated eightfold more blood vessels than did PAECs over a 10-day time course. Heterologous NAP1 expression in PAECs increased the number of blood vessels formed by this cell type, where blood vessel growth approached that seen with PMVECs. Thus, our findings indicate that NAP1 functions as an important regulator of the proliferative and vasculogenic endothelial cell phenotype without globally impacting endothelial cell phenotype specification. angiogenesi