Oligonucleotide Microarrays Identified Potential Regulatory Genes Related to Early Outward Arterial Remodeling Induced by Tissue Plasminogen Activator
Constrictive vascular remodeling limiting blood flow, as well as compensatory outward remodeling, has been observed in many cardiovascular diseases; however, the underlying mechanisms regulating the remodeling response of the vessels remain unclear. Plasminogen activators (PA) are involved in many o...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2019-04-01
|
Series: | Frontiers in Physiology |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2019.00493/full |
_version_ | 1818343894936453120 |
---|---|
author | Olga Plekhanova Olga Plekhanova Yelena Parfyonova Yelena Parfyonova Irina Beloglazova Irina Beloglazova Bradford C. Berk Vsevolod Tkachuk Vsevolod Tkachuk |
author_facet | Olga Plekhanova Olga Plekhanova Yelena Parfyonova Yelena Parfyonova Irina Beloglazova Irina Beloglazova Bradford C. Berk Vsevolod Tkachuk Vsevolod Tkachuk |
author_sort | Olga Plekhanova |
collection | DOAJ |
description | Constrictive vascular remodeling limiting blood flow, as well as compensatory outward remodeling, has been observed in many cardiovascular diseases; however, the underlying mechanisms regulating the remodeling response of the vessels remain unclear. Plasminogen activators (PA) are involved in many of the processes of vascular remodeling. We have shown previously that increased levels of tissue-type PA (tPA) contributes to outward vascular remodeling. To elucidate the mechanisms involved in the induction of outward remodeling we characterized changes in the expression profiles of 8799 genes in injured rat carotid arteries 1 and 4 days after recombinant tPA treatment compared to vehicle. Periadventitial tPA significantly increased lumen size and vessel area, encompassed by the external elastic lamina, at both one and 4 days after treatment. Among 41 differentially expressed known genes 1 day after tPA application, five genes were involved in gene transcription, five genes were related to the regulation of vascular tone [for example, thromboxane A2 receptor (D32080) or non-selective-type endothelin receptor (S65355)], and eight genes were identified as participating in vascular innervation [for example, calpain (D14478) or neural cell adhesion molecule L1 (X59149)]. Four days after injury in tPA-treated arteries, four genes, regulating vascular tone, were differentially expressed. Thus, tPA promotes outward arterial remodeling after injury, at least in part, by regulating expression of genes in the vessel wall related to function of the nervous system and vascular tone. |
first_indexed | 2024-12-13T16:37:50Z |
format | Article |
id | doaj.art-02e39f6d464a41bb80d42777bbe36dae |
institution | Directory Open Access Journal |
issn | 1664-042X |
language | English |
last_indexed | 2024-12-13T16:37:50Z |
publishDate | 2019-04-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Physiology |
spelling | doaj.art-02e39f6d464a41bb80d42777bbe36dae2022-12-21T23:38:21ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2019-04-011010.3389/fphys.2019.00493439628Oligonucleotide Microarrays Identified Potential Regulatory Genes Related to Early Outward Arterial Remodeling Induced by Tissue Plasminogen ActivatorOlga Plekhanova0Olga Plekhanova1Yelena Parfyonova2Yelena Parfyonova3Irina Beloglazova4Irina Beloglazova5Bradford C. Berk6Vsevolod Tkachuk7Vsevolod Tkachuk8Faculty of Medicine, Lomonosov Moscow State University, Moscow, RussiaNational Medical Research Center of Cardiology, Moscow, RussiaFaculty of Medicine, Lomonosov Moscow State University, Moscow, RussiaNational Medical Research Center of Cardiology, Moscow, RussiaFaculty of Medicine, Lomonosov Moscow State University, Moscow, RussiaNational Medical Research Center of Cardiology, Moscow, RussiaAab Cardiovascular Research Institute, University of Rochester Medical Center, Rochester, NY, United StatesFaculty of Medicine, Lomonosov Moscow State University, Moscow, RussiaNational Medical Research Center of Cardiology, Moscow, RussiaConstrictive vascular remodeling limiting blood flow, as well as compensatory outward remodeling, has been observed in many cardiovascular diseases; however, the underlying mechanisms regulating the remodeling response of the vessels remain unclear. Plasminogen activators (PA) are involved in many of the processes of vascular remodeling. We have shown previously that increased levels of tissue-type PA (tPA) contributes to outward vascular remodeling. To elucidate the mechanisms involved in the induction of outward remodeling we characterized changes in the expression profiles of 8799 genes in injured rat carotid arteries 1 and 4 days after recombinant tPA treatment compared to vehicle. Periadventitial tPA significantly increased lumen size and vessel area, encompassed by the external elastic lamina, at both one and 4 days after treatment. Among 41 differentially expressed known genes 1 day after tPA application, five genes were involved in gene transcription, five genes were related to the regulation of vascular tone [for example, thromboxane A2 receptor (D32080) or non-selective-type endothelin receptor (S65355)], and eight genes were identified as participating in vascular innervation [for example, calpain (D14478) or neural cell adhesion molecule L1 (X59149)]. Four days after injury in tPA-treated arteries, four genes, regulating vascular tone, were differentially expressed. Thus, tPA promotes outward arterial remodeling after injury, at least in part, by regulating expression of genes in the vessel wall related to function of the nervous system and vascular tone.https://www.frontiersin.org/article/10.3389/fphys.2019.00493/fulltissue type plasminogen activatoroutward vascular remodelingmicroarrayvascular tonearterial injury |
spellingShingle | Olga Plekhanova Olga Plekhanova Yelena Parfyonova Yelena Parfyonova Irina Beloglazova Irina Beloglazova Bradford C. Berk Vsevolod Tkachuk Vsevolod Tkachuk Oligonucleotide Microarrays Identified Potential Regulatory Genes Related to Early Outward Arterial Remodeling Induced by Tissue Plasminogen Activator Frontiers in Physiology tissue type plasminogen activator outward vascular remodeling microarray vascular tone arterial injury |
title | Oligonucleotide Microarrays Identified Potential Regulatory Genes Related to Early Outward Arterial Remodeling Induced by Tissue Plasminogen Activator |
title_full | Oligonucleotide Microarrays Identified Potential Regulatory Genes Related to Early Outward Arterial Remodeling Induced by Tissue Plasminogen Activator |
title_fullStr | Oligonucleotide Microarrays Identified Potential Regulatory Genes Related to Early Outward Arterial Remodeling Induced by Tissue Plasminogen Activator |
title_full_unstemmed | Oligonucleotide Microarrays Identified Potential Regulatory Genes Related to Early Outward Arterial Remodeling Induced by Tissue Plasminogen Activator |
title_short | Oligonucleotide Microarrays Identified Potential Regulatory Genes Related to Early Outward Arterial Remodeling Induced by Tissue Plasminogen Activator |
title_sort | oligonucleotide microarrays identified potential regulatory genes related to early outward arterial remodeling induced by tissue plasminogen activator |
topic | tissue type plasminogen activator outward vascular remodeling microarray vascular tone arterial injury |
url | https://www.frontiersin.org/article/10.3389/fphys.2019.00493/full |
work_keys_str_mv | AT olgaplekhanova oligonucleotidemicroarraysidentifiedpotentialregulatorygenesrelatedtoearlyoutwardarterialremodelinginducedbytissueplasminogenactivator AT olgaplekhanova oligonucleotidemicroarraysidentifiedpotentialregulatorygenesrelatedtoearlyoutwardarterialremodelinginducedbytissueplasminogenactivator AT yelenaparfyonova oligonucleotidemicroarraysidentifiedpotentialregulatorygenesrelatedtoearlyoutwardarterialremodelinginducedbytissueplasminogenactivator AT yelenaparfyonova oligonucleotidemicroarraysidentifiedpotentialregulatorygenesrelatedtoearlyoutwardarterialremodelinginducedbytissueplasminogenactivator AT irinabeloglazova oligonucleotidemicroarraysidentifiedpotentialregulatorygenesrelatedtoearlyoutwardarterialremodelinginducedbytissueplasminogenactivator AT irinabeloglazova oligonucleotidemicroarraysidentifiedpotentialregulatorygenesrelatedtoearlyoutwardarterialremodelinginducedbytissueplasminogenactivator AT bradfordcberk oligonucleotidemicroarraysidentifiedpotentialregulatorygenesrelatedtoearlyoutwardarterialremodelinginducedbytissueplasminogenactivator AT vsevolodtkachuk oligonucleotidemicroarraysidentifiedpotentialregulatorygenesrelatedtoearlyoutwardarterialremodelinginducedbytissueplasminogenactivator AT vsevolodtkachuk oligonucleotidemicroarraysidentifiedpotentialregulatorygenesrelatedtoearlyoutwardarterialremodelinginducedbytissueplasminogenactivator |