Use of Kv1.3 channel blockers for the prevention of restenosis in human vessels: Mechanisms and outcomes in diabetic patients
Vascular smooth muscle cells (VSMCs) can undergo phenotypic modulation (PM) to a dedifferentiated state, which contributes to angiogenesis and vessel repair. PM is triggered by vascular surgeries such as those directed to unclog obstructed vessels. However, an excessive VSMC migration and proliferat...
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| Formato: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | España |
| Recursos: | Universidad de Valladolid |
| Repositorio: | UVaDOC. Repositorio Documental de la Universidad de Valladolid |
| OAI Identifier: | oai:uvadoc.uva.es:10324/43490 |
| Acesso em linha: | https://doi.org/10.35376/10324/43490 http://uvadoc.uva.es/handle/10324/43490 |
| Access Level: | acceso abierto |
| Palavra-chave: | Kv1.5 Kv1.3 Diabetes 32 Ciencias Médicas |
| Resumo: | Vascular smooth muscle cells (VSMCs) can undergo phenotypic modulation (PM) to a dedifferentiated state, which contributes to angiogenesis and vessel repair. PM is triggered by vascular surgeries such as those directed to unclog obstructed vessels. However, an excessive VSMC migration and proliferation drives intimal hyperplasia (IH) leading to restenosis. This situation is even worse in patients with background diseases like type 2 diabetes mellitus (T2DM). T2DM patients have more aggressive forms of vascular disease and worse outcomes, with exacerbated restenosis after vascular surgery. We have previously demonstrated that an increased functional expression of the potassium channel Kv1.3 contributes to PM in several models of VSMCs, as Kv1.3 blockers inhibit VSMCs migration and proliferation. In addition, we found that Kv1.3 increased activity upon PM is a consequence of Kv1.5 downregulation, so that the changes in Kv1.3 to Kv1.5 ratio can define VSMCs phenotype. |
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