Mice with endothelial cell‐selective adhesion molecule deficiency develop coronary microvascular rarefaction and left ventricle diastolic dysfunction
Abstract Endothelial cell‐selective adhesion molecule (ESAM) regulates inflammatory cell adhesion and transmigration and promotes angiogenesis. Here, we examined the role of ESAM in cardiac vascularization, inflammatory cell infiltration, and left ventricle (LV) diastolic function under basal and he...
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| Format: | Article |
| Language: | English |
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Wiley
2023-03-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.15643 |
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| author | Vadym Buncha Katie Anne Fopiano Liwei Lang Celestine Williams Anatolij Horuzsko Jessica Andrea Filosa Gaston Kapuku Zsolt Bagi |
| author_facet | Vadym Buncha Katie Anne Fopiano Liwei Lang Celestine Williams Anatolij Horuzsko Jessica Andrea Filosa Gaston Kapuku Zsolt Bagi |
| author_sort | Vadym Buncha |
| collection | DOAJ |
| description | Abstract Endothelial cell‐selective adhesion molecule (ESAM) regulates inflammatory cell adhesion and transmigration and promotes angiogenesis. Here, we examined the role of ESAM in cardiac vascularization, inflammatory cell infiltration, and left ventricle (LV) diastolic function under basal and hemodynamic stress conditions. We employed mice with homozygous genetic deletion of ESAM (ESAM−/−) and also performed uninephrectomy and aldosterone infusion (UNX‐Aldo) to induce volume and pressure overload. Using echocardiography, we found that ESAM−/− mice display no change in systolic function. However, they develop LV diastolic dysfunction, as indicated by a significantly reduced E/A ratio (E = early, A = late mitral inflow peak velocities), increased E/e’ ratio, isovolumic relaxation time (IVRT), and E wave deceleration time. An unbiased automated tracing and 3D reconstruction of coronary vasculature revealed that ESAM−/− mice had reduced coronary vascular density. Arteries of ESAM−/− mice exhibited impaired endothelial sprouting and in cultured endothelial cells siRNA‐mediated ESAM knockdown reduced tube formation. Changes in ESAM−/− mice were accompanied by elevated myocardial inflammatory cytokine and myeloperoxidase‐positive neutrophil levels. Furthermore, UNX‐Aldo procedure in wild type mice induced LV diastolic dysfunction, which was accompanied by significantly increased serum ESAM levels. When compared to wild types, ESAM−/− mice with UNX‐Aldo displayed worsening of LV diastolic function, as indicated by increased IVRT and pulmonary edema. Thus, we propose that ESAM plays a mechanistic role in proper myocardial vascularization and the maintenance of LV diastolic function under basal and hemodynamic stress conditions. |
| first_indexed | 2024-03-08T19:17:24Z |
| format | Article |
| id | doaj.art-514d96ab2ffe4a84a50dcbd6f20cd596 |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-03-08T19:17:24Z |
| publishDate | 2023-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-514d96ab2ffe4a84a50dcbd6f20cd5962023-12-27T04:12:43ZengWileyPhysiological Reports2051-817X2023-03-01116n/an/a10.14814/phy2.15643Mice with endothelial cell‐selective adhesion molecule deficiency develop coronary microvascular rarefaction and left ventricle diastolic dysfunctionVadym Buncha0Katie Anne Fopiano1Liwei Lang2Celestine Williams3Anatolij Horuzsko4Jessica Andrea Filosa5Gaston Kapuku6Zsolt Bagi7Department of Physiology Medical College of Georgia, Augusta University Georgia Augusta USADepartment of Physiology Medical College of Georgia, Augusta University Georgia Augusta USADepartment of Physiology Medical College of Georgia, Augusta University Georgia Augusta USADepartment of Medicine Georgia Prevention Institute, Medical College of Georgia, Augusta University Augusta Georgia USAGeorgia Cancer Center Medical College of Georgia, Augusta University Georgia Augusta USADepartment of Physiology Medical College of Georgia, Augusta University Georgia Augusta USADepartment of Medicine Georgia Prevention Institute, Medical College of Georgia, Augusta University Augusta Georgia USADepartment of Physiology Medical College of Georgia, Augusta University Georgia Augusta USAAbstract Endothelial cell‐selective adhesion molecule (ESAM) regulates inflammatory cell adhesion and transmigration and promotes angiogenesis. Here, we examined the role of ESAM in cardiac vascularization, inflammatory cell infiltration, and left ventricle (LV) diastolic function under basal and hemodynamic stress conditions. We employed mice with homozygous genetic deletion of ESAM (ESAM−/−) and also performed uninephrectomy and aldosterone infusion (UNX‐Aldo) to induce volume and pressure overload. Using echocardiography, we found that ESAM−/− mice display no change in systolic function. However, they develop LV diastolic dysfunction, as indicated by a significantly reduced E/A ratio (E = early, A = late mitral inflow peak velocities), increased E/e’ ratio, isovolumic relaxation time (IVRT), and E wave deceleration time. An unbiased automated tracing and 3D reconstruction of coronary vasculature revealed that ESAM−/− mice had reduced coronary vascular density. Arteries of ESAM−/− mice exhibited impaired endothelial sprouting and in cultured endothelial cells siRNA‐mediated ESAM knockdown reduced tube formation. Changes in ESAM−/− mice were accompanied by elevated myocardial inflammatory cytokine and myeloperoxidase‐positive neutrophil levels. Furthermore, UNX‐Aldo procedure in wild type mice induced LV diastolic dysfunction, which was accompanied by significantly increased serum ESAM levels. When compared to wild types, ESAM−/− mice with UNX‐Aldo displayed worsening of LV diastolic function, as indicated by increased IVRT and pulmonary edema. Thus, we propose that ESAM plays a mechanistic role in proper myocardial vascularization and the maintenance of LV diastolic function under basal and hemodynamic stress conditions.https://doi.org/10.14814/phy2.15643angiogenesiscoronarydiastolic dysfunctionHFpEFinflammation |
| spellingShingle | Vadym Buncha Katie Anne Fopiano Liwei Lang Celestine Williams Anatolij Horuzsko Jessica Andrea Filosa Gaston Kapuku Zsolt Bagi Mice with endothelial cell‐selective adhesion molecule deficiency develop coronary microvascular rarefaction and left ventricle diastolic dysfunction Physiological Reports angiogenesis coronary diastolic dysfunction HFpEF inflammation |
| title | Mice with endothelial cell‐selective adhesion molecule deficiency develop coronary microvascular rarefaction and left ventricle diastolic dysfunction |
| title_full | Mice with endothelial cell‐selective adhesion molecule deficiency develop coronary microvascular rarefaction and left ventricle diastolic dysfunction |
| title_fullStr | Mice with endothelial cell‐selective adhesion molecule deficiency develop coronary microvascular rarefaction and left ventricle diastolic dysfunction |
| title_full_unstemmed | Mice with endothelial cell‐selective adhesion molecule deficiency develop coronary microvascular rarefaction and left ventricle diastolic dysfunction |
| title_short | Mice with endothelial cell‐selective adhesion molecule deficiency develop coronary microvascular rarefaction and left ventricle diastolic dysfunction |
| title_sort | mice with endothelial cell selective adhesion molecule deficiency develop coronary microvascular rarefaction and left ventricle diastolic dysfunction |
| topic | angiogenesis coronary diastolic dysfunction HFpEF inflammation |
| url | https://doi.org/10.14814/phy2.15643 |
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