Angiotensin II binding and extracellular matrix remodelling in a rat model of myocardial infarction
Clinical evidence points to a role for angiotensin II (Ang II) in the post-infarction remodelling of cardiac hypertrophy. The present study was designed to investigate the remodelling process in an animal model of myocardial infarction (MI) using the following criteria: 1) histological studies to ex...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publications
2000-12-01
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| Series: | Journal of the Renin-Angiotensin-Aldosterone System |
| Online Access: | https://doi.org/10.3317/jraas.2000.069 |
| _version_ | 1797285418726588416 |
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| author | Marwan E El-Sabban Khaled A Hassan Adel E Birbari Khalil M Bitar Anwar B Bikhazi |
| author_facet | Marwan E El-Sabban Khaled A Hassan Adel E Birbari Khalil M Bitar Anwar B Bikhazi |
| author_sort | Marwan E El-Sabban |
| collection | DOAJ |
| description | Clinical evidence points to a role for angiotensin II (Ang II) in the post-infarction remodelling of cardiac hypertrophy. The present study was designed to investigate the remodelling process in an animal model of myocardial infarction (MI) using the following criteria: 1) histological studies to examine the re-vascularisation process and collagen deposition in different regions of the myocardium; 2) histological evidence to investigate the cell type distribution using cell-specific markers; 3) histological and Western blot analysis to localise Ang II receptor subtypes (AT 1 -receptor and AT 2 -receptor) and to study their regulation; 4) kinetics of the binding of Ang II to its receptors in a heart perfusion model; and 5) to assess the effect of the Ang II antagonist (losartan) on these parameters. MI was induced by ligation of the left anterior descending coronary artery of Sprague-Dawley rats. Four different animal groups were established: 1) sham-operated, non-treated; 2) sham-operated, treated with losartan; 3) myocardial infarct, non-treated; and 4) myocardial infarct, treated with losartan. In infarcted rat hearts, fibroblasts and collagen types I and III increased in the remnant viable region of the left ventricle compared with sham-operated rats. One month of losartan treatment in myocardial infarcted rats revealed insignificant changes in fibroblasts and collagen types I and III compared with sham controls. Also, myocardial infarction increased AT 1 -receptor protein levels compared with sham-operated controls, as judged by Western blotting. In losartan-treated myocardial infarct animals, no changes were detected at the level of AT 1 -receptor expression compared with non-treated myocardial infarct rats. Binding studies of Ang II on endothelial cell lining and directly on myocytes in sham-operated and infarcted perfused rat hearts revealed that, in myocardial infarcted-animals, Ang II binding affinity increased both in the endothelium and in myofibres. This may be considered a major putative effect of the peptide in potentiating the pharmacodynamics of hypertrophy. In losartan-treated myocardial infarcted-animals, a marked increase in the binding affinities of Ang II for the AT 2 -receptor subtype was observed. Hence, potential cardioprotective effects of the AT 1 -receptor antagonist are proposed. |
| first_indexed | 2024-03-07T18:02:56Z |
| format | Article |
| id | doaj.art-bf6f70941503438c97a69ab6795e5170 |
| institution | Directory Open Access Journal |
| issn | 1470-3203 |
| language | English |
| last_indexed | 2024-03-07T18:02:56Z |
| publishDate | 2000-12-01 |
| publisher | SAGE Publications |
| record_format | Article |
| series | Journal of the Renin-Angiotensin-Aldosterone System |
| spelling | doaj.art-bf6f70941503438c97a69ab6795e51702024-03-02T10:24:28ZengSAGE PublicationsJournal of the Renin-Angiotensin-Aldosterone System1470-32032000-12-01110.3317/jraas.2000.069Angiotensin II binding and extracellular matrix remodelling in a rat model of myocardial infarctionMarwan E El-SabbanKhaled A HassanAdel E BirbariKhalil M BitarAnwar B BikhaziClinical evidence points to a role for angiotensin II (Ang II) in the post-infarction remodelling of cardiac hypertrophy. The present study was designed to investigate the remodelling process in an animal model of myocardial infarction (MI) using the following criteria: 1) histological studies to examine the re-vascularisation process and collagen deposition in different regions of the myocardium; 2) histological evidence to investigate the cell type distribution using cell-specific markers; 3) histological and Western blot analysis to localise Ang II receptor subtypes (AT 1 -receptor and AT 2 -receptor) and to study their regulation; 4) kinetics of the binding of Ang II to its receptors in a heart perfusion model; and 5) to assess the effect of the Ang II antagonist (losartan) on these parameters. MI was induced by ligation of the left anterior descending coronary artery of Sprague-Dawley rats. Four different animal groups were established: 1) sham-operated, non-treated; 2) sham-operated, treated with losartan; 3) myocardial infarct, non-treated; and 4) myocardial infarct, treated with losartan. In infarcted rat hearts, fibroblasts and collagen types I and III increased in the remnant viable region of the left ventricle compared with sham-operated rats. One month of losartan treatment in myocardial infarcted rats revealed insignificant changes in fibroblasts and collagen types I and III compared with sham controls. Also, myocardial infarction increased AT 1 -receptor protein levels compared with sham-operated controls, as judged by Western blotting. In losartan-treated myocardial infarct animals, no changes were detected at the level of AT 1 -receptor expression compared with non-treated myocardial infarct rats. Binding studies of Ang II on endothelial cell lining and directly on myocytes in sham-operated and infarcted perfused rat hearts revealed that, in myocardial infarcted-animals, Ang II binding affinity increased both in the endothelium and in myofibres. This may be considered a major putative effect of the peptide in potentiating the pharmacodynamics of hypertrophy. In losartan-treated myocardial infarcted-animals, a marked increase in the binding affinities of Ang II for the AT 2 -receptor subtype was observed. Hence, potential cardioprotective effects of the AT 1 -receptor antagonist are proposed.https://doi.org/10.3317/jraas.2000.069 |
| spellingShingle | Marwan E El-Sabban Khaled A Hassan Adel E Birbari Khalil M Bitar Anwar B Bikhazi Angiotensin II binding and extracellular matrix remodelling in a rat model of myocardial infarction Journal of the Renin-Angiotensin-Aldosterone System |
| title | Angiotensin II binding and extracellular matrix remodelling in a rat model of myocardial infarction |
| title_full | Angiotensin II binding and extracellular matrix remodelling in a rat model of myocardial infarction |
| title_fullStr | Angiotensin II binding and extracellular matrix remodelling in a rat model of myocardial infarction |
| title_full_unstemmed | Angiotensin II binding and extracellular matrix remodelling in a rat model of myocardial infarction |
| title_short | Angiotensin II binding and extracellular matrix remodelling in a rat model of myocardial infarction |
| title_sort | angiotensin ii binding and extracellular matrix remodelling in a rat model of myocardial infarction |
| url | https://doi.org/10.3317/jraas.2000.069 |
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