Loading…
Control of Proliferation of Human Vascular Endothelial Cells: Characterization of the Response of Human Umbilical Vein Endothelial Cells to Fibroblast Growth Factor, Epidermal Growth Factor, and Thrombin
Because the response of human endothelial cells to growth factors and conditioning agents has broad implications for our understanding of wound healing, angiogenesis, and human atherogenesis, we have investigated the responses of these cells to the fibroblast (FGF) and epidermal growth factors (EGF)...
Saved in:
Published in: | The Journal of cell biology 1978-06, Vol.77 (3), p.774-788 |
---|---|
Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c465t-aebd85218ef8f911f2353a39327a029ed7fad94548ad40101dc7ccb2e0b97f713 |
---|---|
cites | |
container_end_page | 788 |
container_issue | 3 |
container_start_page | 774 |
container_title | The Journal of cell biology |
container_volume | 77 |
creator | Gospodarowicz, Denis Brown, Kenneth D. Birdwell, Charles R. Zetter, Bruce R. |
description | Because the response of human endothelial cells to growth factors and conditioning agents has broad implications for our understanding of wound healing, angiogenesis, and human atherogenesis, we have investigated the responses of these cells to the fibroblast (FGF) and epidermal growth factors (EGF), as well as to the protease thrombin, which has been previously shown to potentiate the growth response of other cell types of FGF and EGF. Because the vascular endothelial cells that form the inner lining of blood vessels may be expected to be exposed to high thrombin concentrations after trauma or in pathological states associated with thrombosis, they are of particular interest with respect to the physiological role of this protease in potentiating cell proliferation. Our results indicate that human vascular endothelial cells respond poorly to either FGF or thrombin alone. In contrast, when cells are maintained in the presence of thrombin, their proliferative response to FGF is greatly increased even in cultures seeded at a density as low as 3 cells/ mm2. Human vascular endothelial cells also respond to EGF and thrombin, although their rate of proliferation is much slower than when maintained with FGF and thrombin. In contrast, bovine vascular endothelial cells derived from vascular territories as diverse as the bovine heart, aortic arch, and umbilical vein respond maximally to FGF alone and neither respond to nor bind EGF. Furthermore, the response of bovine vascular endothelial cells to FGF was not potentiated by thrombin, indicating that the set of factors controlling the proliferation of vascular endothelial cells could be species-dependent. The requirement of cultured human vascular endothelial cells for thrombin could explain why the human cells, in contrast to bovine endothelial cells, are so difficult to maintain in tissue culture. Our results demonstrate that by using FGF and thrombin one can develop cultures of human vascular endothelial cells capable of being passage repeatedly while maintaining a high mitotic index. The stock cultures used for these studies have been passed weekly with a split ratio of 1 to 10 and are currently in their 30th passage. These cultures are indistinguishable from earlier passages when examined for the presence of Weibel-Palade bodies or Factor VIII antigen. We conclude that the use of FGF and thrombin can prevent the precocious senescence observed in most human endothelial cell cultures previously described. |
doi_str_mv | 10.1083/jcb.77.3.774 |
format | article |
fullrecord | <record><control><sourceid>jstor_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2110143</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>1608467</jstor_id><sourcerecordid>1608467</sourcerecordid><originalsourceid>FETCH-LOGICAL-c465t-aebd85218ef8f911f2353a39327a029ed7fad94548ad40101dc7ccb2e0b97f713</originalsourceid><addsrcrecordid>eNplkU1v1DAQhi3E11K4ceTgE6dmsWMnTjggoWi3RaoEQm2v1sSxiVeOvdgJCP4ifwpXW-3ycZmR_L7zjDUvQi8pWVPSsDc71a-FWLNc-AO0ohUnRUM5eYhWhJS0aKuyeoqepbQjhHDB2RP0mJGG1PUK_eqCn2NwOBj8KXdrdITZBn_3cLlM4PEtJLU4iHjjhzCP2llwuNPOpbe4GyGCmnW0P49T2YI_67QPPukT5WbqrbMqj95q6_9n4Tngre1j6B2kGV_E8H0e8TbDQzzHm70ddJyy-R8B_ICvxxgy3T9Hjwy4pF_c9zN0s91cd5fF1ceLD937q0LxupoL0P3QVCVttGlMS6kpWcWAtawUQMpWD8LA0PKKNzBwQgkdlFCqLzXpW2EEZWfo3YG7X_pJD0rnC4KT-2gniD9kACv_Vrwd5ZfwTZY00zjLgNf3gBi-LjrNcrJJ5SuA12FJUnDCWsHbbDw_GFUMKUVtjksokXfZy5y9FEKyXHi2v_rzY0fzIeyTvEv5didUTRpeC_YbYWu5Jg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>74039749</pqid></control><display><type>article</type><title>Control of Proliferation of Human Vascular Endothelial Cells: Characterization of the Response of Human Umbilical Vein Endothelial Cells to Fibroblast Growth Factor, Epidermal Growth Factor, and Thrombin</title><source>JSTOR Archival Journals and Primary Sources Collection</source><creator>Gospodarowicz, Denis ; Brown, Kenneth D. ; Birdwell, Charles R. ; Zetter, Bruce R.</creator><creatorcontrib>Gospodarowicz, Denis ; Brown, Kenneth D. ; Birdwell, Charles R. ; Zetter, Bruce R.</creatorcontrib><description>Because the response of human endothelial cells to growth factors and conditioning agents has broad implications for our understanding of wound healing, angiogenesis, and human atherogenesis, we have investigated the responses of these cells to the fibroblast (FGF) and epidermal growth factors (EGF), as well as to the protease thrombin, which has been previously shown to potentiate the growth response of other cell types of FGF and EGF. Because the vascular endothelial cells that form the inner lining of blood vessels may be expected to be exposed to high thrombin concentrations after trauma or in pathological states associated with thrombosis, they are of particular interest with respect to the physiological role of this protease in potentiating cell proliferation. Our results indicate that human vascular endothelial cells respond poorly to either FGF or thrombin alone. In contrast, when cells are maintained in the presence of thrombin, their proliferative response to FGF is greatly increased even in cultures seeded at a density as low as 3 cells/ mm2. Human vascular endothelial cells also respond to EGF and thrombin, although their rate of proliferation is much slower than when maintained with FGF and thrombin. In contrast, bovine vascular endothelial cells derived from vascular territories as diverse as the bovine heart, aortic arch, and umbilical vein respond maximally to FGF alone and neither respond to nor bind EGF. Furthermore, the response of bovine vascular endothelial cells to FGF was not potentiated by thrombin, indicating that the set of factors controlling the proliferation of vascular endothelial cells could be species-dependent. The requirement of cultured human vascular endothelial cells for thrombin could explain why the human cells, in contrast to bovine endothelial cells, are so difficult to maintain in tissue culture. Our results demonstrate that by using FGF and thrombin one can develop cultures of human vascular endothelial cells capable of being passage repeatedly while maintaining a high mitotic index. The stock cultures used for these studies have been passed weekly with a split ratio of 1 to 10 and are currently in their 30th passage. These cultures are indistinguishable from earlier passages when examined for the presence of Weibel-Palade bodies or Factor VIII antigen. We conclude that the use of FGF and thrombin can prevent the precocious senescence observed in most human endothelial cell cultures previously described.</description><identifier>ISSN: 0021-9525</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.77.3.774</identifier><identifier>PMID: 308066</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Animals ; Aorta, Thoracic ; Cattle ; Cell Division - drug effects ; Cell growth ; Cell lines ; Cells ; Culture Techniques ; Cultured cells ; Endothelial cells ; Endothelium - cytology ; Endothelium - drug effects ; Epidermal Growth Factor - pharmacology ; Epithelial cells ; Fetal Heart ; Growth Substances - pharmacology ; Human umbilical vein endothelial cells ; Humans ; Peptides - pharmacology ; Pituitary Hormones - pharmacology ; Thoracic aorta ; Thrombin - pharmacology ; Umbilical Veins ; Ungulates</subject><ispartof>The Journal of cell biology, 1978-06, Vol.77 (3), p.774-788</ispartof><rights>Copyright 1978 The Rockefeller University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c465t-aebd85218ef8f911f2353a39327a029ed7fad94548ad40101dc7ccb2e0b97f713</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/1608467$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/1608467$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,58213,58446</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/308066$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gospodarowicz, Denis</creatorcontrib><creatorcontrib>Brown, Kenneth D.</creatorcontrib><creatorcontrib>Birdwell, Charles R.</creatorcontrib><creatorcontrib>Zetter, Bruce R.</creatorcontrib><title>Control of Proliferation of Human Vascular Endothelial Cells: Characterization of the Response of Human Umbilical Vein Endothelial Cells to Fibroblast Growth Factor, Epidermal Growth Factor, and Thrombin</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><description>Because the response of human endothelial cells to growth factors and conditioning agents has broad implications for our understanding of wound healing, angiogenesis, and human atherogenesis, we have investigated the responses of these cells to the fibroblast (FGF) and epidermal growth factors (EGF), as well as to the protease thrombin, which has been previously shown to potentiate the growth response of other cell types of FGF and EGF. Because the vascular endothelial cells that form the inner lining of blood vessels may be expected to be exposed to high thrombin concentrations after trauma or in pathological states associated with thrombosis, they are of particular interest with respect to the physiological role of this protease in potentiating cell proliferation. Our results indicate that human vascular endothelial cells respond poorly to either FGF or thrombin alone. In contrast, when cells are maintained in the presence of thrombin, their proliferative response to FGF is greatly increased even in cultures seeded at a density as low as 3 cells/ mm2. Human vascular endothelial cells also respond to EGF and thrombin, although their rate of proliferation is much slower than when maintained with FGF and thrombin. In contrast, bovine vascular endothelial cells derived from vascular territories as diverse as the bovine heart, aortic arch, and umbilical vein respond maximally to FGF alone and neither respond to nor bind EGF. Furthermore, the response of bovine vascular endothelial cells to FGF was not potentiated by thrombin, indicating that the set of factors controlling the proliferation of vascular endothelial cells could be species-dependent. The requirement of cultured human vascular endothelial cells for thrombin could explain why the human cells, in contrast to bovine endothelial cells, are so difficult to maintain in tissue culture. Our results demonstrate that by using FGF and thrombin one can develop cultures of human vascular endothelial cells capable of being passage repeatedly while maintaining a high mitotic index. The stock cultures used for these studies have been passed weekly with a split ratio of 1 to 10 and are currently in their 30th passage. These cultures are indistinguishable from earlier passages when examined for the presence of Weibel-Palade bodies or Factor VIII antigen. We conclude that the use of FGF and thrombin can prevent the precocious senescence observed in most human endothelial cell cultures previously described.</description><subject>Animals</subject><subject>Aorta, Thoracic</subject><subject>Cattle</subject><subject>Cell Division - drug effects</subject><subject>Cell growth</subject><subject>Cell lines</subject><subject>Cells</subject><subject>Culture Techniques</subject><subject>Cultured cells</subject><subject>Endothelial cells</subject><subject>Endothelium - cytology</subject><subject>Endothelium - drug effects</subject><subject>Epidermal Growth Factor - pharmacology</subject><subject>Epithelial cells</subject><subject>Fetal Heart</subject><subject>Growth Substances - pharmacology</subject><subject>Human umbilical vein endothelial cells</subject><subject>Humans</subject><subject>Peptides - pharmacology</subject><subject>Pituitary Hormones - pharmacology</subject><subject>Thoracic aorta</subject><subject>Thrombin - pharmacology</subject><subject>Umbilical Veins</subject><subject>Ungulates</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1978</creationdate><recordtype>article</recordtype><recordid>eNplkU1v1DAQhi3E11K4ceTgE6dmsWMnTjggoWi3RaoEQm2v1sSxiVeOvdgJCP4ifwpXW-3ycZmR_L7zjDUvQi8pWVPSsDc71a-FWLNc-AO0ohUnRUM5eYhWhJS0aKuyeoqepbQjhHDB2RP0mJGG1PUK_eqCn2NwOBj8KXdrdITZBn_3cLlM4PEtJLU4iHjjhzCP2llwuNPOpbe4GyGCmnW0P49T2YI_67QPPukT5WbqrbMqj95q6_9n4Tngre1j6B2kGV_E8H0e8TbDQzzHm70ddJyy-R8B_ICvxxgy3T9Hjwy4pF_c9zN0s91cd5fF1ceLD937q0LxupoL0P3QVCVttGlMS6kpWcWAtawUQMpWD8LA0PKKNzBwQgkdlFCqLzXpW2EEZWfo3YG7X_pJD0rnC4KT-2gniD9kACv_Vrwd5ZfwTZY00zjLgNf3gBi-LjrNcrJJ5SuA12FJUnDCWsHbbDw_GFUMKUVtjksokXfZy5y9FEKyXHi2v_rzY0fzIeyTvEv5didUTRpeC_YbYWu5Jg</recordid><startdate>19780601</startdate><enddate>19780601</enddate><creator>Gospodarowicz, Denis</creator><creator>Brown, Kenneth D.</creator><creator>Birdwell, Charles R.</creator><creator>Zetter, Bruce R.</creator><general>Rockefeller University Press</general><general>The Rockefeller University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19780601</creationdate><title>Control of Proliferation of Human Vascular Endothelial Cells: Characterization of the Response of Human Umbilical Vein Endothelial Cells to Fibroblast Growth Factor, Epidermal Growth Factor, and Thrombin</title><author>Gospodarowicz, Denis ; Brown, Kenneth D. ; Birdwell, Charles R. ; Zetter, Bruce R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c465t-aebd85218ef8f911f2353a39327a029ed7fad94548ad40101dc7ccb2e0b97f713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1978</creationdate><topic>Animals</topic><topic>Aorta, Thoracic</topic><topic>Cattle</topic><topic>Cell Division - drug effects</topic><topic>Cell growth</topic><topic>Cell lines</topic><topic>Cells</topic><topic>Culture Techniques</topic><topic>Cultured cells</topic><topic>Endothelial cells</topic><topic>Endothelium - cytology</topic><topic>Endothelium - drug effects</topic><topic>Epidermal Growth Factor - pharmacology</topic><topic>Epithelial cells</topic><topic>Fetal Heart</topic><topic>Growth Substances - pharmacology</topic><topic>Human umbilical vein endothelial cells</topic><topic>Humans</topic><topic>Peptides - pharmacology</topic><topic>Pituitary Hormones - pharmacology</topic><topic>Thoracic aorta</topic><topic>Thrombin - pharmacology</topic><topic>Umbilical Veins</topic><topic>Ungulates</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gospodarowicz, Denis</creatorcontrib><creatorcontrib>Brown, Kenneth D.</creatorcontrib><creatorcontrib>Birdwell, Charles R.</creatorcontrib><creatorcontrib>Zetter, Bruce R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gospodarowicz, Denis</au><au>Brown, Kenneth D.</au><au>Birdwell, Charles R.</au><au>Zetter, Bruce R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Control of Proliferation of Human Vascular Endothelial Cells: Characterization of the Response of Human Umbilical Vein Endothelial Cells to Fibroblast Growth Factor, Epidermal Growth Factor, and Thrombin</atitle><jtitle>The Journal of cell biology</jtitle><addtitle>J Cell Biol</addtitle><date>1978-06-01</date><risdate>1978</risdate><volume>77</volume><issue>3</issue><spage>774</spage><epage>788</epage><pages>774-788</pages><issn>0021-9525</issn><eissn>1540-8140</eissn><abstract>Because the response of human endothelial cells to growth factors and conditioning agents has broad implications for our understanding of wound healing, angiogenesis, and human atherogenesis, we have investigated the responses of these cells to the fibroblast (FGF) and epidermal growth factors (EGF), as well as to the protease thrombin, which has been previously shown to potentiate the growth response of other cell types of FGF and EGF. Because the vascular endothelial cells that form the inner lining of blood vessels may be expected to be exposed to high thrombin concentrations after trauma or in pathological states associated with thrombosis, they are of particular interest with respect to the physiological role of this protease in potentiating cell proliferation. Our results indicate that human vascular endothelial cells respond poorly to either FGF or thrombin alone. In contrast, when cells are maintained in the presence of thrombin, their proliferative response to FGF is greatly increased even in cultures seeded at a density as low as 3 cells/ mm2. Human vascular endothelial cells also respond to EGF and thrombin, although their rate of proliferation is much slower than when maintained with FGF and thrombin. In contrast, bovine vascular endothelial cells derived from vascular territories as diverse as the bovine heart, aortic arch, and umbilical vein respond maximally to FGF alone and neither respond to nor bind EGF. Furthermore, the response of bovine vascular endothelial cells to FGF was not potentiated by thrombin, indicating that the set of factors controlling the proliferation of vascular endothelial cells could be species-dependent. The requirement of cultured human vascular endothelial cells for thrombin could explain why the human cells, in contrast to bovine endothelial cells, are so difficult to maintain in tissue culture. Our results demonstrate that by using FGF and thrombin one can develop cultures of human vascular endothelial cells capable of being passage repeatedly while maintaining a high mitotic index. The stock cultures used for these studies have been passed weekly with a split ratio of 1 to 10 and are currently in their 30th passage. These cultures are indistinguishable from earlier passages when examined for the presence of Weibel-Palade bodies or Factor VIII antigen. We conclude that the use of FGF and thrombin can prevent the precocious senescence observed in most human endothelial cell cultures previously described.</abstract><cop>United States</cop><pub>Rockefeller University Press</pub><pmid>308066</pmid><doi>10.1083/jcb.77.3.774</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0021-9525 |
ispartof | The Journal of cell biology, 1978-06, Vol.77 (3), p.774-788 |
issn | 0021-9525 1540-8140 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2110143 |
source | JSTOR Archival Journals and Primary Sources Collection |
subjects | Animals Aorta, Thoracic Cattle Cell Division - drug effects Cell growth Cell lines Cells Culture Techniques Cultured cells Endothelial cells Endothelium - cytology Endothelium - drug effects Epidermal Growth Factor - pharmacology Epithelial cells Fetal Heart Growth Substances - pharmacology Human umbilical vein endothelial cells Humans Peptides - pharmacology Pituitary Hormones - pharmacology Thoracic aorta Thrombin - pharmacology Umbilical Veins Ungulates |
title | Control of Proliferation of Human Vascular Endothelial Cells: Characterization of the Response of Human Umbilical Vein Endothelial Cells to Fibroblast Growth Factor, Epidermal Growth Factor, and Thrombin |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T08%3A30%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Control%20of%20Proliferation%20of%20Human%20Vascular%20Endothelial%20Cells:%20Characterization%20of%20the%20Response%20of%20Human%20Umbilical%20Vein%20Endothelial%20Cells%20to%20Fibroblast%20Growth%20Factor,%20Epidermal%20Growth%20Factor,%20and%20Thrombin&rft.jtitle=The%20Journal%20of%20cell%20biology&rft.au=Gospodarowicz,%20Denis&rft.date=1978-06-01&rft.volume=77&rft.issue=3&rft.spage=774&rft.epage=788&rft.pages=774-788&rft.issn=0021-9525&rft.eissn=1540-8140&rft_id=info:doi/10.1083/jcb.77.3.774&rft_dat=%3Cjstor_pubme%3E1608467%3C/jstor_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c465t-aebd85218ef8f911f2353a39327a029ed7fad94548ad40101dc7ccb2e0b97f713%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=74039749&rft_id=info:pmid/308066&rft_jstor_id=1608467&rfr_iscdi=true |