Endothelial Glycocalyx of Peritubular Capillaries in Experimental Diabetic Nephropathy: A Target of ACE Inhibitor-Induced Kidney Microvascular Protection
Peritubular capillary rarefaction is a recurrent aspect of progressive nephropathies. We previously found that peritubular capillary density was reduced in BTBR <i>ob</i>/<i>ob</i> mice with type 2 diabetic nephropathy. In this model, we searched for abnormalities in the ultr...
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MDPI AG
2023-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/22/16543 |
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| author | Monica Locatelli Daniela Rottoli Rayan Mahmoud Mauro Abbate Daniela Corna Domenico Cerullo Susanna Tomasoni Giuseppe Remuzzi Carlamaria Zoja Ariela Benigni Daniela Macconi |
| author_facet | Monica Locatelli Daniela Rottoli Rayan Mahmoud Mauro Abbate Daniela Corna Domenico Cerullo Susanna Tomasoni Giuseppe Remuzzi Carlamaria Zoja Ariela Benigni Daniela Macconi |
| author_sort | Monica Locatelli |
| collection | DOAJ |
| description | Peritubular capillary rarefaction is a recurrent aspect of progressive nephropathies. We previously found that peritubular capillary density was reduced in BTBR <i>ob</i>/<i>ob</i> mice with type 2 diabetic nephropathy. In this model, we searched for abnormalities in the ultrastructure of peritubular capillaries, with a specific focus on the endothelial glycocalyx, and evaluated the impact of treatment with an angiotensin-converting enzyme inhibitor (ACEi). Mice were intracardially perfused with lanthanum to visualise the glycocalyx. Transmission electron microscopy analysis revealed endothelial cell abnormalities and basement membrane thickening in the peritubular capillaries of BTBR <i>ob</i>/<i>ob</i> mice compared to wild-type mice. Remodelling and focal loss of glycocalyx was observed in lanthanum-stained diabetic kidneys, associated with a reduction in glycocalyx components, including sialic acids, as detected through specific lectins. ACEi treatment preserved the endothelial glycocalyx and attenuated the ultrastructural abnormalities of peritubular capillaries. In diabetic mice, peritubular capillary damage was associated with an enhanced tubular expression of heparanase, which degrades heparan sulfate residues of the glycocalyx. Heparanase was also detected in renal interstitial macrophages that expressed tumor necrosis factor-α. All these abnormalities were mitigated by ACEi. Our findings suggest that, in experimental diabetic nephropathy, preserving the endothelial glycocalyx is important in order to protect peritubular capillaries from damage and loss. |
| first_indexed | 2024-03-09T16:45:30Z |
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| language | English |
| last_indexed | 2024-03-09T16:45:30Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ef2e6dc15b4645879253904262d6b5e12023-11-24T14:48:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124221654310.3390/ijms242216543Endothelial Glycocalyx of Peritubular Capillaries in Experimental Diabetic Nephropathy: A Target of ACE Inhibitor-Induced Kidney Microvascular ProtectionMonica Locatelli0Daniela Rottoli1Rayan Mahmoud2Mauro Abbate3Daniela Corna4Domenico Cerullo5Susanna Tomasoni6Giuseppe Remuzzi7Carlamaria Zoja8Ariela Benigni9Daniela Macconi10Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, 24126 Bergamo, ItalyIstituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, 24126 Bergamo, ItalyIstituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, 24126 Bergamo, ItalyIstituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, 24126 Bergamo, ItalyIstituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, 24126 Bergamo, ItalyIstituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, 24126 Bergamo, ItalyIstituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, 24126 Bergamo, ItalyIstituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, 24126 Bergamo, ItalyIstituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, 24126 Bergamo, ItalyIstituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, 24126 Bergamo, ItalyIstituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, 24126 Bergamo, ItalyPeritubular capillary rarefaction is a recurrent aspect of progressive nephropathies. We previously found that peritubular capillary density was reduced in BTBR <i>ob</i>/<i>ob</i> mice with type 2 diabetic nephropathy. In this model, we searched for abnormalities in the ultrastructure of peritubular capillaries, with a specific focus on the endothelial glycocalyx, and evaluated the impact of treatment with an angiotensin-converting enzyme inhibitor (ACEi). Mice were intracardially perfused with lanthanum to visualise the glycocalyx. Transmission electron microscopy analysis revealed endothelial cell abnormalities and basement membrane thickening in the peritubular capillaries of BTBR <i>ob</i>/<i>ob</i> mice compared to wild-type mice. Remodelling and focal loss of glycocalyx was observed in lanthanum-stained diabetic kidneys, associated with a reduction in glycocalyx components, including sialic acids, as detected through specific lectins. ACEi treatment preserved the endothelial glycocalyx and attenuated the ultrastructural abnormalities of peritubular capillaries. In diabetic mice, peritubular capillary damage was associated with an enhanced tubular expression of heparanase, which degrades heparan sulfate residues of the glycocalyx. Heparanase was also detected in renal interstitial macrophages that expressed tumor necrosis factor-α. All these abnormalities were mitigated by ACEi. Our findings suggest that, in experimental diabetic nephropathy, preserving the endothelial glycocalyx is important in order to protect peritubular capillaries from damage and loss.https://www.mdpi.com/1422-0067/24/22/16543diabetic nephropathyperitubular capillaryendothelial glycocalyxangiotensin-converting enzyme inhibitor |
| spellingShingle | Monica Locatelli Daniela Rottoli Rayan Mahmoud Mauro Abbate Daniela Corna Domenico Cerullo Susanna Tomasoni Giuseppe Remuzzi Carlamaria Zoja Ariela Benigni Daniela Macconi Endothelial Glycocalyx of Peritubular Capillaries in Experimental Diabetic Nephropathy: A Target of ACE Inhibitor-Induced Kidney Microvascular Protection International Journal of Molecular Sciences diabetic nephropathy peritubular capillary endothelial glycocalyx angiotensin-converting enzyme inhibitor |
| title | Endothelial Glycocalyx of Peritubular Capillaries in Experimental Diabetic Nephropathy: A Target of ACE Inhibitor-Induced Kidney Microvascular Protection |
| title_full | Endothelial Glycocalyx of Peritubular Capillaries in Experimental Diabetic Nephropathy: A Target of ACE Inhibitor-Induced Kidney Microvascular Protection |
| title_fullStr | Endothelial Glycocalyx of Peritubular Capillaries in Experimental Diabetic Nephropathy: A Target of ACE Inhibitor-Induced Kidney Microvascular Protection |
| title_full_unstemmed | Endothelial Glycocalyx of Peritubular Capillaries in Experimental Diabetic Nephropathy: A Target of ACE Inhibitor-Induced Kidney Microvascular Protection |
| title_short | Endothelial Glycocalyx of Peritubular Capillaries in Experimental Diabetic Nephropathy: A Target of ACE Inhibitor-Induced Kidney Microvascular Protection |
| title_sort | endothelial glycocalyx of peritubular capillaries in experimental diabetic nephropathy a target of ace inhibitor induced kidney microvascular protection |
| topic | diabetic nephropathy peritubular capillary endothelial glycocalyx angiotensin-converting enzyme inhibitor |
| url | https://www.mdpi.com/1422-0067/24/22/16543 |
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