Cerebral adaptations to chronic anemia in a model of erythropoietin-deficient mice exposed to hypoxia
Anemia and hypoxia in rats result in an increase in factors potentially involved in cerebral angiogenesis. Therefore, the aim of this study was to assess the effect of chronic anemia and/or chronic hypoxia on cerebral cellular responses and angiogenesis in wild-type and anemic transgenic mice. These...
Uloženo v:
| Vydáno v: | American journal of physiology. Regulatory, integrative and comparative physiology Ročník 296; číslo 3; s. R801 |
|---|---|
| Hlavní autoři: | , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
01.03.2009
|
| Témata: | |
| ISSN: | 0363-6119 |
| On-line přístup: | Zjistit podrobnosti o přístupu |
| Tagy: |
Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
|
| Abstract | Anemia and hypoxia in rats result in an increase in factors potentially involved in cerebral angiogenesis. Therefore, the aim of this study was to assess the effect of chronic anemia and/or chronic hypoxia on cerebral cellular responses and angiogenesis in wild-type and anemic transgenic mice. These studies were done in erythropoietin-deficient mice (Epo-TAg(h)) in normoxia and following acute (one day) and chronic (14 days, barometric pressure = 420 mmHg) hypoxia. In normoxia, Epo-TAg(h) mice showed an increase in transcript and protein levels of hypoxia-inducible factor 1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), erythropoietin receptors (EpoR), phospho-STAT-5/STAT-5 ratio, and neuronal neuronal nitric oxide synthase (nNOS) along with a higher cerebral capillary density. In wild-type (WT) mice, acute hypoxia increased all of the studied factors, while in chronic hypoxia, HIF-1alpha, EpoR, phospho-STAT-5/STAT-5 ratio, nNOS, and inducible NOS remained elevated, with an increase in capillary density. Surprisingly, in Epo-TAg(h) mice, chronic hypoxia did not further increase any factor except the nitric oxide metabolites, while HIF-1alpha, EpoR, and phospho-STAT-5/STAT-5 ratio were reduced. Normoxic Epo-TAg(h) mice developed cerebral angiogenesis through the HIF-1alpha/VEGF pathway. In acute hypoxia, WT mice up-regulated all of the studied factors, including cerebral NO. Polycythemia and angiogenesis occurred with acclimatization to chronic hypoxia only in WT mice. In Epo-TAg(h), the decrease in HIF-1alpha, VEGF proteins, and phospho-STAT-5 ratio in chronic hypoxia suggest that neuroprotective and angiogenesis pathways are altered. |
|---|---|
| AbstractList | Anemia and hypoxia in rats result in an increase in factors potentially involved in cerebral angiogenesis. Therefore, the aim of this study was to assess the effect of chronic anemia and/or chronic hypoxia on cerebral cellular responses and angiogenesis in wild-type and anemic transgenic mice. These studies were done in erythropoietin-deficient mice (Epo-TAg(h)) in normoxia and following acute (one day) and chronic (14 days, barometric pressure = 420 mmHg) hypoxia. In normoxia, Epo-TAg(h) mice showed an increase in transcript and protein levels of hypoxia-inducible factor 1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), erythropoietin receptors (EpoR), phospho-STAT-5/STAT-5 ratio, and neuronal neuronal nitric oxide synthase (nNOS) along with a higher cerebral capillary density. In wild-type (WT) mice, acute hypoxia increased all of the studied factors, while in chronic hypoxia, HIF-1alpha, EpoR, phospho-STAT-5/STAT-5 ratio, nNOS, and inducible NOS remained elevated, with an increase in capillary density. Surprisingly, in Epo-TAg(h) mice, chronic hypoxia did not further increase any factor except the nitric oxide metabolites, while HIF-1alpha, EpoR, and phospho-STAT-5/STAT-5 ratio were reduced. Normoxic Epo-TAg(h) mice developed cerebral angiogenesis through the HIF-1alpha/VEGF pathway. In acute hypoxia, WT mice up-regulated all of the studied factors, including cerebral NO. Polycythemia and angiogenesis occurred with acclimatization to chronic hypoxia only in WT mice. In Epo-TAg(h), the decrease in HIF-1alpha, VEGF proteins, and phospho-STAT-5 ratio in chronic hypoxia suggest that neuroprotective and angiogenesis pathways are altered.Anemia and hypoxia in rats result in an increase in factors potentially involved in cerebral angiogenesis. Therefore, the aim of this study was to assess the effect of chronic anemia and/or chronic hypoxia on cerebral cellular responses and angiogenesis in wild-type and anemic transgenic mice. These studies were done in erythropoietin-deficient mice (Epo-TAg(h)) in normoxia and following acute (one day) and chronic (14 days, barometric pressure = 420 mmHg) hypoxia. In normoxia, Epo-TAg(h) mice showed an increase in transcript and protein levels of hypoxia-inducible factor 1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), erythropoietin receptors (EpoR), phospho-STAT-5/STAT-5 ratio, and neuronal neuronal nitric oxide synthase (nNOS) along with a higher cerebral capillary density. In wild-type (WT) mice, acute hypoxia increased all of the studied factors, while in chronic hypoxia, HIF-1alpha, EpoR, phospho-STAT-5/STAT-5 ratio, nNOS, and inducible NOS remained elevated, with an increase in capillary density. Surprisingly, in Epo-TAg(h) mice, chronic hypoxia did not further increase any factor except the nitric oxide metabolites, while HIF-1alpha, EpoR, and phospho-STAT-5/STAT-5 ratio were reduced. Normoxic Epo-TAg(h) mice developed cerebral angiogenesis through the HIF-1alpha/VEGF pathway. In acute hypoxia, WT mice up-regulated all of the studied factors, including cerebral NO. Polycythemia and angiogenesis occurred with acclimatization to chronic hypoxia only in WT mice. In Epo-TAg(h), the decrease in HIF-1alpha, VEGF proteins, and phospho-STAT-5 ratio in chronic hypoxia suggest that neuroprotective and angiogenesis pathways are altered. Anemia and hypoxia in rats result in an increase in factors potentially involved in cerebral angiogenesis. Therefore, the aim of this study was to assess the effect of chronic anemia and/or chronic hypoxia on cerebral cellular responses and angiogenesis in wild-type and anemic transgenic mice. These studies were done in erythropoietin-deficient mice (Epo-TAg(h)) in normoxia and following acute (one day) and chronic (14 days, barometric pressure = 420 mmHg) hypoxia. In normoxia, Epo-TAg(h) mice showed an increase in transcript and protein levels of hypoxia-inducible factor 1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), erythropoietin receptors (EpoR), phospho-STAT-5/STAT-5 ratio, and neuronal neuronal nitric oxide synthase (nNOS) along with a higher cerebral capillary density. In wild-type (WT) mice, acute hypoxia increased all of the studied factors, while in chronic hypoxia, HIF-1alpha, EpoR, phospho-STAT-5/STAT-5 ratio, nNOS, and inducible NOS remained elevated, with an increase in capillary density. Surprisingly, in Epo-TAg(h) mice, chronic hypoxia did not further increase any factor except the nitric oxide metabolites, while HIF-1alpha, EpoR, and phospho-STAT-5/STAT-5 ratio were reduced. Normoxic Epo-TAg(h) mice developed cerebral angiogenesis through the HIF-1alpha/VEGF pathway. In acute hypoxia, WT mice up-regulated all of the studied factors, including cerebral NO. Polycythemia and angiogenesis occurred with acclimatization to chronic hypoxia only in WT mice. In Epo-TAg(h), the decrease in HIF-1alpha, VEGF proteins, and phospho-STAT-5 ratio in chronic hypoxia suggest that neuroprotective and angiogenesis pathways are altered. |
| Author | Duvallet, Alain Pichon, Aurélien Quidu, Patricia El Hasnaoui-Saadani, Raja Launay, Thierry Marchant, Dominique Olivier, Paul Beaudry, Michèle Richalet, Jean-Paul Favret, Fabrice |
| Author_xml | – sequence: 1 givenname: Raja surname: El Hasnaoui-Saadani fullname: El Hasnaoui-Saadani, Raja organization: Université Paris, Bobigny, France – sequence: 2 givenname: Aurélien surname: Pichon fullname: Pichon, Aurélien – sequence: 3 givenname: Dominique surname: Marchant fullname: Marchant, Dominique – sequence: 4 givenname: Paul surname: Olivier fullname: Olivier, Paul – sequence: 5 givenname: Thierry surname: Launay fullname: Launay, Thierry – sequence: 6 givenname: Patricia surname: Quidu fullname: Quidu, Patricia – sequence: 7 givenname: Michèle surname: Beaudry fullname: Beaudry, Michèle – sequence: 8 givenname: Alain surname: Duvallet fullname: Duvallet, Alain – sequence: 9 givenname: Jean-Paul surname: Richalet fullname: Richalet, Jean-Paul – sequence: 10 givenname: Fabrice surname: Favret fullname: Favret, Fabrice |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/19109375$$D View this record in MEDLINE/PubMed |
| BookMark | eNo1kD1PwzAYhD0U0VL4AwzIE1uKHcdOPKKKL6kSC8yRP95QV4kdbEdq_z1BlOmku0cn3V2hhQ8eELqlZEMpLx_UYYzwNW0IoVRuSkKaBVoRJlghZmOJrlI6EEIqVrFLtKSSEslqvkKwhQg6qh4rq8assgs-4Ryw2cfgncHKw-AUdh4rPAQLPQ4dhnjKcz4GB9n5wkLnjAOf8eAMYDiOIYH9bdmfxnB06hpddKpPcHPWNfp8fvrYvha795e37eOuMExWuWCqkcAt4byS0tQKKqEBlKa6sbrWteANJcKAAavZnFSUcVF2UndWmabryjW6_-sdY_ieIOV2cMlA388rwpRaIaTggtAZvDuDkx7AtmN0g4qn9v-Y8gdzCGmU |
| CitedBy_id | crossref_primary_10_1111_trf_13703 crossref_primary_10_1053_j_jvca_2011_07_024 crossref_primary_10_1371_journal_pone_0029378 crossref_primary_10_1016_j_resp_2013_01_003 crossref_primary_10_1007_s12630_009_9201_z crossref_primary_10_1016_j_biopha_2021_111547 crossref_primary_10_1155_2010_137817 crossref_primary_10_3389_fphys_2022_850418 crossref_primary_10_3390_ijms18071519 crossref_primary_10_1007_s12630_012_9861_y crossref_primary_10_1073_pnas_1114026108 crossref_primary_10_1016_j_aquatox_2017_10_003 crossref_primary_10_1016_j_resp_2017_04_003 crossref_primary_10_1002_jmri_27210 crossref_primary_10_1093_bja_aer350 crossref_primary_10_1016_j_resp_2017_07_002 crossref_primary_10_1089_ham_2013_1121 crossref_primary_10_1111_trf_12565 crossref_primary_10_1002_phy2_223 crossref_primary_10_3389_fphys_2024_1293247 crossref_primary_10_1016_j_stem_2011_07_001 crossref_primary_10_1007_s00424_009_0775_7 crossref_primary_10_1186_s13034_020_00352_4 crossref_primary_10_1016_j_anclin_2016_06_007 crossref_primary_10_1016_j_bpa_2012_12_002 crossref_primary_10_1053_j_jvca_2017_11_043 |
| ContentType | Journal Article |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1152/ajpregu.00119.2008 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Anatomy & Physiology |
| ExternalDocumentID | 19109375 |
| Genre | Research Support, Non-U.S. Gov't Journal Article |
| GroupedDBID | 23M 2WC 39C 4.4 53G 5GY 5VS 6J9 8M5 AAFWJ ACIWK ACPRK ADBBV AFFNX AFRAH ALMA_UNASSIGNED_HOLDINGS BAWUL BKKCC BKOMP BTFSW C1A CGR CUY CVF EBS ECM EIF EJD EMOBN F5P H13 ITBOX KQ8 NPM OK1 P2P PQQKQ RAP RHI RPL RPRKH TAE TR2 UKR W8F WH7 WOQ XSW YSK YYP ~02 7X8 |
| ID | FETCH-LOGICAL-c394t-3a89e5d055499c7ae46beeab1b8db7b7658106cecedb3bee413562f9bfdac8ff2 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 35 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000263745200037&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 0363-6119 |
| IngestDate | Sun Nov 09 12:46:09 EST 2025 Thu Apr 03 06:59:33 EDT 2025 |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 3 |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c394t-3a89e5d055499c7ae46beeab1b8db7b7658106cecedb3bee413562f9bfdac8ff2 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| PMID | 19109375 |
| PQID | 66965601 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_66965601 pubmed_primary_19109375 |
| PublicationCentury | 2000 |
| PublicationDate | 2009-Mar 20090301 |
| PublicationDateYYYYMMDD | 2009-03-01 |
| PublicationDate_xml | – month: 03 year: 2009 text: 2009-Mar |
| PublicationDecade | 2000 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | American journal of physiology. Regulatory, integrative and comparative physiology |
| PublicationTitleAlternate | Am J Physiol Regul Integr Comp Physiol |
| PublicationYear | 2009 |
| SSID | ssj0004343 |
| Score | 2.0932734 |
| Snippet | Anemia and hypoxia in rats result in an increase in factors potentially involved in cerebral angiogenesis. Therefore, the aim of this study was to assess the... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | R801 |
| SubjectTerms | Anemia - physiopathology Animals Body Weight - physiology Brain - physiopathology Cerebral Cortex - metabolism Chronic Disease Erythropoietin - deficiency Erythropoietin - genetics Erythropoietin - metabolism Hemoglobins - metabolism Hypoxia - physiopathology Hypoxia-Inducible Factor 1, alpha Subunit - biosynthesis Hypoxia-Inducible Factor 1, alpha Subunit - genetics Immunoassay Immunohistochemistry Male Mice Mice, Inbred CBA Mice, Knockout Nitric Oxide - metabolism Receptors, Erythropoietin - biosynthesis Receptors, Erythropoietin - genetics Reverse Transcriptase Polymerase Chain Reaction RNA - biosynthesis RNA - isolation & purification STAT5 Transcription Factor - metabolism Vascular Endothelial Growth Factor A - metabolism |
| Title | Cerebral adaptations to chronic anemia in a model of erythropoietin-deficient mice exposed to hypoxia |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/19109375 https://www.proquest.com/docview/66965601 |
| Volume | 296 |
| WOSCitedRecordID | wos000263745200037&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV07T8MwELYKZWDhVR7l6QGxRU3qJE4kJFQhKgaoOgDqVvlxgSCahLRF7b_n7DQSC2JgyRIlSuyz7z5_d_cRcokrJkR8EziqKxCgRB5zpHQjJ0HX6fpcMm21CF4e-GAQjUbxsEGu61oYk1ZZ74l2o9a5MmfknTCMTZ8Y76b4dIxmlOFWVwIaa6TJMJAxNs1HP3qFsypnzjCVoefFdclM0O2I96KE17mlIWy1SvR7gGkdTX_7f5-4Q7ZWASbtVRaxSxqQ7ZFWL0NwPVnSK2pTPu1ZeovALZSGOP6gQouiIuWndJZTVbXMpSKDSSpomlFBrWYOzRMK5bISV0hNubSjwTShQN9FjbI9hUWRT0Gbt7wti3yRin3y3L97ur13VroLjmKxP3OYiGIItBsY7Ki4AD-UAEJ6MtKSS45BCwJJBQq0ZHgH_SBGUUksEy1UlCTdA7Ke5RkcERoHXGuZRDrgzPf9QHAGAhFNLFwNTMs2uaiHcox2bcgK_LN8Ph3Xg9kmh9VsjIuq_cYYEaaLQVVw_OezJ2SzIn9MytgpaSa4ouGMbKivWTotz6254HUwfPwG74HNhg |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Cerebral+adaptations+to+chronic+anemia+in+a+model+of+erythropoietin-deficient+mice+exposed+to+hypoxia&rft.jtitle=American+journal+of+physiology.+Regulatory%2C+integrative+and+comparative+physiology&rft.au=El+Hasnaoui-Saadani%2C+Raja&rft.au=Pichon%2C+Aur%C3%A9lien&rft.au=Marchant%2C+Dominique&rft.au=Olivier%2C+Paul&rft.date=2009-03-01&rft.issn=0363-6119&rft.volume=296&rft.issue=3&rft.spage=R801&rft_id=info:doi/10.1152%2Fajpregu.00119.2008&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0363-6119&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0363-6119&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0363-6119&client=summon |