Angiotensin II-Induced Cardiovascular Fibrosis Is Attenuated by NO-Sensitive Guanylyl Cyclase1
In the NO/cGMP signaling cascade, relevant in the cardiovascular system, two NO-sensitive guanylyl cyclase (NO-GC) isoforms are responsible for NO-dependent cGMP generation. Here, the impact of the major NO-GC isoform, NO-GC1, on fibrosis development in the cardiovascular system was studied in NO-GC...
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MDPI AG
2020-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/11/2436 |
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| author | Kathrin Broekmans Jan Giesen Lukas Menges Doris Koesling Michael Russwurm |
| author_facet | Kathrin Broekmans Jan Giesen Lukas Menges Doris Koesling Michael Russwurm |
| author_sort | Kathrin Broekmans |
| collection | DOAJ |
| description | In the NO/cGMP signaling cascade, relevant in the cardiovascular system, two NO-sensitive guanylyl cyclase (NO-GC) isoforms are responsible for NO-dependent cGMP generation. Here, the impact of the major NO-GC isoform, NO-GC1, on fibrosis development in the cardiovascular system was studied in NO-GC1-deficient mice treated with AngiotensinII (AngII), known to induce vascular and cardiac remodeling. Morphometric analysis of NO-GC1 KO’s aortae demonstrated an enhanced increase of perivascular area after AngII treatment accompanied by a higher aortic collagen1 mRNA content. Increased perivascular fibrosis also occurred in cardiac vessels of AngII-treated NO-GC1 KO mice. In line, AngII-induced interstitial fibrosis was 32% more pronounced in NO-GC1 KO than in WT myocardia associated with a higher cardiac Col1 and other fibrotic marker protein content. In sum, increased perivascular and cardiac interstitial fibrosis together with the enhanced collagen1 mRNA content in AngII-treated NO-GC1-deficient mice represent an exciting manifestation of antifibrotic properties of cGMP formed by NO-GC1, a finding with great pharmaco-therapeutic implications. |
| first_indexed | 2024-03-10T15:01:34Z |
| format | Article |
| id | doaj.art-e44c1c6a1db84540819bdd4f158db93a |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T15:01:34Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-e44c1c6a1db84540819bdd4f158db93a2023-11-20T20:11:48ZengMDPI AGCells2073-44092020-11-01911243610.3390/cells9112436Angiotensin II-Induced Cardiovascular Fibrosis Is Attenuated by NO-Sensitive Guanylyl Cyclase1Kathrin Broekmans0Jan Giesen1Lukas Menges2Doris Koesling3Michael Russwurm4Institut für Pharmakologie und Toxikologie, Med. Fak. MA N1, Ruhr-Universität Bochum, 44780 Bochum, GermanyInstitut für Pharmakologie und Toxikologie, Med. Fak. MA N1, Ruhr-Universität Bochum, 44780 Bochum, GermanyInstitut für Pharmakologie und Toxikologie, Med. Fak. MA N1, Ruhr-Universität Bochum, 44780 Bochum, GermanyInstitut für Pharmakologie und Toxikologie, Med. Fak. MA N1, Ruhr-Universität Bochum, 44780 Bochum, GermanyInstitut für Pharmakologie und Toxikologie, Med. Fak. MA N1, Ruhr-Universität Bochum, 44780 Bochum, GermanyIn the NO/cGMP signaling cascade, relevant in the cardiovascular system, two NO-sensitive guanylyl cyclase (NO-GC) isoforms are responsible for NO-dependent cGMP generation. Here, the impact of the major NO-GC isoform, NO-GC1, on fibrosis development in the cardiovascular system was studied in NO-GC1-deficient mice treated with AngiotensinII (AngII), known to induce vascular and cardiac remodeling. Morphometric analysis of NO-GC1 KO’s aortae demonstrated an enhanced increase of perivascular area after AngII treatment accompanied by a higher aortic collagen1 mRNA content. Increased perivascular fibrosis also occurred in cardiac vessels of AngII-treated NO-GC1 KO mice. In line, AngII-induced interstitial fibrosis was 32% more pronounced in NO-GC1 KO than in WT myocardia associated with a higher cardiac Col1 and other fibrotic marker protein content. In sum, increased perivascular and cardiac interstitial fibrosis together with the enhanced collagen1 mRNA content in AngII-treated NO-GC1-deficient mice represent an exciting manifestation of antifibrotic properties of cGMP formed by NO-GC1, a finding with great pharmaco-therapeutic implications.https://www.mdpi.com/2073-4409/9/11/2436angiotensinnitric oxideguanylyl cyclasecGMP |
| spellingShingle | Kathrin Broekmans Jan Giesen Lukas Menges Doris Koesling Michael Russwurm Angiotensin II-Induced Cardiovascular Fibrosis Is Attenuated by NO-Sensitive Guanylyl Cyclase1 Cells angiotensin nitric oxide guanylyl cyclase cGMP |
| title | Angiotensin II-Induced Cardiovascular Fibrosis Is Attenuated by NO-Sensitive Guanylyl Cyclase1 |
| title_full | Angiotensin II-Induced Cardiovascular Fibrosis Is Attenuated by NO-Sensitive Guanylyl Cyclase1 |
| title_fullStr | Angiotensin II-Induced Cardiovascular Fibrosis Is Attenuated by NO-Sensitive Guanylyl Cyclase1 |
| title_full_unstemmed | Angiotensin II-Induced Cardiovascular Fibrosis Is Attenuated by NO-Sensitive Guanylyl Cyclase1 |
| title_short | Angiotensin II-Induced Cardiovascular Fibrosis Is Attenuated by NO-Sensitive Guanylyl Cyclase1 |
| title_sort | angiotensin ii induced cardiovascular fibrosis is attenuated by no sensitive guanylyl cyclase1 |
| topic | angiotensin nitric oxide guanylyl cyclase cGMP |
| url | https://www.mdpi.com/2073-4409/9/11/2436 |
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