High Soluble Endoglin Levels Affect Aortic Vascular Function during Mice Aging
Endoglin is a 180 kDa transmembrane glycoprotein that was demonstrated to be present in two different endoglin forms, namely membrane endoglin (Eng) and soluble endoglin (sEng). Increased sEng levels in the circulation have been detected in atherosclerosis, arterial hypertension, and type II diabete...
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MDPI AG
2021-12-01
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| Series: | Journal of Cardiovascular Development and Disease |
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| Online Access: | https://www.mdpi.com/2308-3425/8/12/173 |
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| author | Iveta Nejmanová Barbora Vitverová Samira Eissazadeh Katarina Tripská Ivone Cristina Igreja Sa Radomír Hyšpler Ivana Němečkova Miguel Pericacho Petr Nachtigal |
| author_facet | Iveta Nejmanová Barbora Vitverová Samira Eissazadeh Katarina Tripská Ivone Cristina Igreja Sa Radomír Hyšpler Ivana Němečkova Miguel Pericacho Petr Nachtigal |
| author_sort | Iveta Nejmanová |
| collection | DOAJ |
| description | Endoglin is a 180 kDa transmembrane glycoprotein that was demonstrated to be present in two different endoglin forms, namely membrane endoglin (Eng) and soluble endoglin (sEng). Increased sEng levels in the circulation have been detected in atherosclerosis, arterial hypertension, and type II diabetes mellitus. Moreover, sEng was shown to aggravate endothelial dysfunction when combined with a high-fat diet, suggesting it might be a risk factor for the development of endothelial dysfunction in combination with other risk factors. Therefore, this study hypothesized that high sEng levels exposure for 12 months combined with aging (an essential risk factor of atherosclerosis development) would aggravate vascular function in mouse aorta. Male transgenic mice with high levels of human sEng in plasma (Sol-Eng<sup>+</sup>) and their age-matched male transgenic littermates that do not develop high soluble endoglin (Control) on a chow diet were used. The aging process was initiated to contribute to endothelial dysfunction/atherosclerosis development, and it lasted 12 months. Wire myograph analysis showed impairment contractility in the Sol-Eng<sup>+</sup> group when compared to the control group after KCl and PGF<sub>2</sub><sub>α</sub> administration. Endothelium-dependent responsiveness to Ach was not significantly different between these groups. Western blot analysis revealed significantly decreased protein expression of Eng, p-eNOS, and ID1 expression in the Sol-Eng<sup>+</sup> group compared to the control group suggesting reduced Eng signaling. In conclusion, we demonstrated for the first time that long-term exposure to high levels of sEng during aging results in alteration of vasoconstriction properties of the aorta, reduced eNOS phosphorylation, decreased Eng expression, and altered Eng signaling. These findings suggest that sEng can be considered a risk factor for the development of vascular dysfunction during aging and a potential therapeutical target for pharmacological intervention. |
| first_indexed | 2024-03-10T03:52:15Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2308-3425 |
| language | English |
| last_indexed | 2024-03-10T03:52:15Z |
| publishDate | 2021-12-01 |
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| series | Journal of Cardiovascular Development and Disease |
| spelling | doaj.art-fb45bfcea7f44f50866f1ed99d6668e02023-11-23T08:54:55ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252021-12-0181217310.3390/jcdd8120173High Soluble Endoglin Levels Affect Aortic Vascular Function during Mice AgingIveta Nejmanová0Barbora Vitverová1Samira Eissazadeh2Katarina Tripská3Ivone Cristina Igreja Sa4Radomír Hyšpler5Ivana Němečkova6Miguel Pericacho7Petr Nachtigal8Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech RepublicDepartment of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech RepublicDepartment of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech RepublicDepartment of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech RepublicDepartment of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech RepublicCentrum for Research and Development, University Hospital, 500 05 Hradec Kralove, Czech RepublicDepartment of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech RepublicRenal and Cardiovascular Research Unit, Department of Physiology and Pharmacology, Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, 37007 Salamanca, SpainDepartment of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech RepublicEndoglin is a 180 kDa transmembrane glycoprotein that was demonstrated to be present in two different endoglin forms, namely membrane endoglin (Eng) and soluble endoglin (sEng). Increased sEng levels in the circulation have been detected in atherosclerosis, arterial hypertension, and type II diabetes mellitus. Moreover, sEng was shown to aggravate endothelial dysfunction when combined with a high-fat diet, suggesting it might be a risk factor for the development of endothelial dysfunction in combination with other risk factors. Therefore, this study hypothesized that high sEng levels exposure for 12 months combined with aging (an essential risk factor of atherosclerosis development) would aggravate vascular function in mouse aorta. Male transgenic mice with high levels of human sEng in plasma (Sol-Eng<sup>+</sup>) and their age-matched male transgenic littermates that do not develop high soluble endoglin (Control) on a chow diet were used. The aging process was initiated to contribute to endothelial dysfunction/atherosclerosis development, and it lasted 12 months. Wire myograph analysis showed impairment contractility in the Sol-Eng<sup>+</sup> group when compared to the control group after KCl and PGF<sub>2</sub><sub>α</sub> administration. Endothelium-dependent responsiveness to Ach was not significantly different between these groups. Western blot analysis revealed significantly decreased protein expression of Eng, p-eNOS, and ID1 expression in the Sol-Eng<sup>+</sup> group compared to the control group suggesting reduced Eng signaling. In conclusion, we demonstrated for the first time that long-term exposure to high levels of sEng during aging results in alteration of vasoconstriction properties of the aorta, reduced eNOS phosphorylation, decreased Eng expression, and altered Eng signaling. These findings suggest that sEng can be considered a risk factor for the development of vascular dysfunction during aging and a potential therapeutical target for pharmacological intervention.https://www.mdpi.com/2308-3425/8/12/173soluble endoglinendoglin signalingvascular functionmice |
| spellingShingle | Iveta Nejmanová Barbora Vitverová Samira Eissazadeh Katarina Tripská Ivone Cristina Igreja Sa Radomír Hyšpler Ivana Němečkova Miguel Pericacho Petr Nachtigal High Soluble Endoglin Levels Affect Aortic Vascular Function during Mice Aging Journal of Cardiovascular Development and Disease soluble endoglin endoglin signaling vascular function mice |
| title | High Soluble Endoglin Levels Affect Aortic Vascular Function during Mice Aging |
| title_full | High Soluble Endoglin Levels Affect Aortic Vascular Function during Mice Aging |
| title_fullStr | High Soluble Endoglin Levels Affect Aortic Vascular Function during Mice Aging |
| title_full_unstemmed | High Soluble Endoglin Levels Affect Aortic Vascular Function during Mice Aging |
| title_short | High Soluble Endoglin Levels Affect Aortic Vascular Function during Mice Aging |
| title_sort | high soluble endoglin levels affect aortic vascular function during mice aging |
| topic | soluble endoglin endoglin signaling vascular function mice |
| url | https://www.mdpi.com/2308-3425/8/12/173 |
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