Role of endothelin in the induction of cardiac hypertrophy in vitro.
Endothelin (ET-1) is a peptide hormone mediating a wide variety of biological processes and is associated with development of cardiac dysfunction. Generally, ET-1 is regarded as a molecular marker released only in correlation with the observation of a hypertrophic response or in conjunction with oth...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3422284?pdf=render |
| _version_ | 1819213204444676096 |
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| author | Tepmanas Bupha-Intr Kaylan M Haizlip Paul M L Janssen |
| author_facet | Tepmanas Bupha-Intr Kaylan M Haizlip Paul M L Janssen |
| author_sort | Tepmanas Bupha-Intr |
| collection | DOAJ |
| description | Endothelin (ET-1) is a peptide hormone mediating a wide variety of biological processes and is associated with development of cardiac dysfunction. Generally, ET-1 is regarded as a molecular marker released only in correlation with the observation of a hypertrophic response or in conjunction with other hypertrophic stress. Although the cardiac hypertrophic effect of ET-1 is demonstrated, inotropic properties of cardiac muscle during chronic ET-1-induced hypertrophy remain largely unclear. Through the use of a novel in vitro multicellular culture system, changes in contractile force and kinetics of rabbit cardiac trabeculae in response to 1 nM ET-1 for 24 hours can be observed. Compared to the initial force at t = 0 hours, ET-1 treated muscles showed a ~2.5 fold increase in developed force after 24 hours without any effect on time to peak contraction or time to 90% relaxation. ET-1 increased muscle diameter by 12.5 ± 3.2% from the initial size, due to increased cell width compared to non-ET-1 treated muscles. Using specific signaling antagonists, inhibition of NCX, CaMKII, MAPKK, and IP3 could attenuate the effect of ET-1 on increased developed force. However, among these inhibitions only IP3 receptor blocker could not prevent the increase muscle size by ET-1. Interestingly, though calcineurin-NFAT inhibition could not suppress the effect of ET-1 on force development, it did prevent muscle hypertrophy. These findings suggest that ET-1 provokes both inotropic and hypertrophic activations on myocardium in which both activations share the same signaling pathway through MAPK and CaMKII in associated with NCX activity. |
| first_indexed | 2024-12-23T06:55:09Z |
| format | Article |
| id | doaj.art-7e128206d0a1441881dd311fe89369dd |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T06:55:09Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7e128206d0a1441881dd311fe89369dd2022-12-21T17:56:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4317910.1371/journal.pone.0043179Role of endothelin in the induction of cardiac hypertrophy in vitro.Tepmanas Bupha-IntrKaylan M HaizlipPaul M L JanssenEndothelin (ET-1) is a peptide hormone mediating a wide variety of biological processes and is associated with development of cardiac dysfunction. Generally, ET-1 is regarded as a molecular marker released only in correlation with the observation of a hypertrophic response or in conjunction with other hypertrophic stress. Although the cardiac hypertrophic effect of ET-1 is demonstrated, inotropic properties of cardiac muscle during chronic ET-1-induced hypertrophy remain largely unclear. Through the use of a novel in vitro multicellular culture system, changes in contractile force and kinetics of rabbit cardiac trabeculae in response to 1 nM ET-1 for 24 hours can be observed. Compared to the initial force at t = 0 hours, ET-1 treated muscles showed a ~2.5 fold increase in developed force after 24 hours without any effect on time to peak contraction or time to 90% relaxation. ET-1 increased muscle diameter by 12.5 ± 3.2% from the initial size, due to increased cell width compared to non-ET-1 treated muscles. Using specific signaling antagonists, inhibition of NCX, CaMKII, MAPKK, and IP3 could attenuate the effect of ET-1 on increased developed force. However, among these inhibitions only IP3 receptor blocker could not prevent the increase muscle size by ET-1. Interestingly, though calcineurin-NFAT inhibition could not suppress the effect of ET-1 on force development, it did prevent muscle hypertrophy. These findings suggest that ET-1 provokes both inotropic and hypertrophic activations on myocardium in which both activations share the same signaling pathway through MAPK and CaMKII in associated with NCX activity.http://europepmc.org/articles/PMC3422284?pdf=render |
| spellingShingle | Tepmanas Bupha-Intr Kaylan M Haizlip Paul M L Janssen Role of endothelin in the induction of cardiac hypertrophy in vitro. PLoS ONE |
| title | Role of endothelin in the induction of cardiac hypertrophy in vitro. |
| title_full | Role of endothelin in the induction of cardiac hypertrophy in vitro. |
| title_fullStr | Role of endothelin in the induction of cardiac hypertrophy in vitro. |
| title_full_unstemmed | Role of endothelin in the induction of cardiac hypertrophy in vitro. |
| title_short | Role of endothelin in the induction of cardiac hypertrophy in vitro. |
| title_sort | role of endothelin in the induction of cardiac hypertrophy in vitro |
| url | http://europepmc.org/articles/PMC3422284?pdf=render |
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