Angiotensin-(1–7) Receptor Mas Deficiency Does Not Exacerbate Cardiac Atrophy Following High-Level Spinal Cord Injury in Mice
Experimental spinal cord injury (SCI) causes a morphological and functional deterioration of the heart, in which the renin–angiotensin system (RAS) might play a role. The recently discovered non-canonical axis of RAS with angiotensin-(1–7) and its receptor Mas, which is associated with cardioprotect...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-03-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2020.00203/full |
| _version_ | 1818854221688078336 |
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| author | Anne Järve Anne Järve Fatimunnisa Qadri Mihail Todiras Mihail Todiras Shirley Schmolke Natalia Alenina Natalia Alenina Michael Bader Michael Bader Michael Bader Michael Bader |
| author_facet | Anne Järve Anne Järve Fatimunnisa Qadri Mihail Todiras Mihail Todiras Shirley Schmolke Natalia Alenina Natalia Alenina Michael Bader Michael Bader Michael Bader Michael Bader |
| author_sort | Anne Järve |
| collection | DOAJ |
| description | Experimental spinal cord injury (SCI) causes a morphological and functional deterioration of the heart, in which the renin–angiotensin system (RAS) might play a role. The recently discovered non-canonical axis of RAS with angiotensin-(1–7) and its receptor Mas, which is associated with cardioprotection could be essential to prevent damage to the heart following SCI. We investigated the cardiac consequences of SCI and the role of Mas in female wild-type (WT, n = 22) and mice deficient of Mas (Mas–/–, n = 25) which underwent spinal cord transection at thoracic level T4 (T4-Tx) or sham-operation by echocardiography (0, 7, 21, and 28 days post-SCI), histology and gene expression analysis at 1 or 2 months post-SCI. We found left ventricular mass reduction with preserved ejection fraction (EF) and fractional shortening in WT as well as Mas–/– mice. Cardiac output was reduced in Mas–/– mice, whereas stroke volume (SV) was reduced in WT T4-Tx mice. Echocardiographic indices did not differ between the genotypes. Smaller heart weight (HW) and smaller cardiomyocyte diameter at 1 month post-SCI compared to sham mice was independent of genotype. The muscle-specific E3 ubiquitin ligases Atrogin-1/MAFbx and MuRF1 were upregulated or showed a trend for upregulation in WT mice at 2 months post-SCI, respectively. Angiotensinogen gene expression was upregulated at 1 month post-SCI and angiotensin II receptor type 2 downregulated at 2 month post-SCI in Mas–/– mice. Mas was downregulated post-SCI. Cardiac atrophy following SCI, not exacerbated by lack of Mas, is a physiological reaction as there were no signs of cardiac pathology and dysfunction. |
| first_indexed | 2024-12-19T07:49:16Z |
| format | Article |
| id | doaj.art-f207d01beffb4fbdb5446767bcfccc92 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-19T07:49:16Z |
| publishDate | 2020-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-f207d01beffb4fbdb5446767bcfccc922022-12-21T20:30:15ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-03-011110.3389/fphys.2020.00203512398Angiotensin-(1–7) Receptor Mas Deficiency Does Not Exacerbate Cardiac Atrophy Following High-Level Spinal Cord Injury in MiceAnne Järve0Anne Järve1Fatimunnisa Qadri2Mihail Todiras3Mihail Todiras4Shirley Schmolke5Natalia Alenina6Natalia Alenina7Michael Bader8Michael Bader9Michael Bader10Michael Bader11Max Delbrück Center for Molecular Medicine, Helmholtz Association of German Research Centers, Berlin, GermanyPartner Site Berlin, German Center for Cardiovascular Research, Berlin, GermanyMax Delbrück Center for Molecular Medicine, Helmholtz Association of German Research Centers, Berlin, GermanyMax Delbrück Center for Molecular Medicine, Helmholtz Association of German Research Centers, Berlin, GermanyNicolae Testemiţanu State University of Medicine and Pharmacy, Chişinãu, MoldovaMax Delbrück Center for Molecular Medicine, Helmholtz Association of German Research Centers, Berlin, GermanyMax Delbrück Center for Molecular Medicine, Helmholtz Association of German Research Centers, Berlin, GermanyPartner Site Berlin, German Center for Cardiovascular Research, Berlin, GermanyMax Delbrück Center for Molecular Medicine, Helmholtz Association of German Research Centers, Berlin, GermanyPartner Site Berlin, German Center for Cardiovascular Research, Berlin, GermanyCharité Universitätsmedizin Berlin, Berlin, GermanyInstitute for Biology, University of Lübeck, Lübeck, GermanyExperimental spinal cord injury (SCI) causes a morphological and functional deterioration of the heart, in which the renin–angiotensin system (RAS) might play a role. The recently discovered non-canonical axis of RAS with angiotensin-(1–7) and its receptor Mas, which is associated with cardioprotection could be essential to prevent damage to the heart following SCI. We investigated the cardiac consequences of SCI and the role of Mas in female wild-type (WT, n = 22) and mice deficient of Mas (Mas–/–, n = 25) which underwent spinal cord transection at thoracic level T4 (T4-Tx) or sham-operation by echocardiography (0, 7, 21, and 28 days post-SCI), histology and gene expression analysis at 1 or 2 months post-SCI. We found left ventricular mass reduction with preserved ejection fraction (EF) and fractional shortening in WT as well as Mas–/– mice. Cardiac output was reduced in Mas–/– mice, whereas stroke volume (SV) was reduced in WT T4-Tx mice. Echocardiographic indices did not differ between the genotypes. Smaller heart weight (HW) and smaller cardiomyocyte diameter at 1 month post-SCI compared to sham mice was independent of genotype. The muscle-specific E3 ubiquitin ligases Atrogin-1/MAFbx and MuRF1 were upregulated or showed a trend for upregulation in WT mice at 2 months post-SCI, respectively. Angiotensinogen gene expression was upregulated at 1 month post-SCI and angiotensin II receptor type 2 downregulated at 2 month post-SCI in Mas–/– mice. Mas was downregulated post-SCI. Cardiac atrophy following SCI, not exacerbated by lack of Mas, is a physiological reaction as there were no signs of cardiac pathology and dysfunction.https://www.frontiersin.org/article/10.3389/fphys.2020.00203/fullrenin–angiotensin systemcardiac atrophyatrogenessympathetic nervous systemfibrosis |
| spellingShingle | Anne Järve Anne Järve Fatimunnisa Qadri Mihail Todiras Mihail Todiras Shirley Schmolke Natalia Alenina Natalia Alenina Michael Bader Michael Bader Michael Bader Michael Bader Angiotensin-(1–7) Receptor Mas Deficiency Does Not Exacerbate Cardiac Atrophy Following High-Level Spinal Cord Injury in Mice Frontiers in Physiology renin–angiotensin system cardiac atrophy atrogenes sympathetic nervous system fibrosis |
| title | Angiotensin-(1–7) Receptor Mas Deficiency Does Not Exacerbate Cardiac Atrophy Following High-Level Spinal Cord Injury in Mice |
| title_full | Angiotensin-(1–7) Receptor Mas Deficiency Does Not Exacerbate Cardiac Atrophy Following High-Level Spinal Cord Injury in Mice |
| title_fullStr | Angiotensin-(1–7) Receptor Mas Deficiency Does Not Exacerbate Cardiac Atrophy Following High-Level Spinal Cord Injury in Mice |
| title_full_unstemmed | Angiotensin-(1–7) Receptor Mas Deficiency Does Not Exacerbate Cardiac Atrophy Following High-Level Spinal Cord Injury in Mice |
| title_short | Angiotensin-(1–7) Receptor Mas Deficiency Does Not Exacerbate Cardiac Atrophy Following High-Level Spinal Cord Injury in Mice |
| title_sort | angiotensin 1 7 receptor mas deficiency does not exacerbate cardiac atrophy following high level spinal cord injury in mice |
| topic | renin–angiotensin system cardiac atrophy atrogenes sympathetic nervous system fibrosis |
| url | https://www.frontiersin.org/article/10.3389/fphys.2020.00203/full |
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