2026-04-14T15:41:17Zhttps://uvadoc.uva.es/oai/request
oai:uvadoc.uva.es:10324/390052024-12-18T07:40:04Zcom_10324_32522com_10324_952com_10324_894com_10324_43677com_10324_954com_10324_1134com_10324_931col_10324_32523col_10324_43678col_10324_1213
UVaDOC author Arévalo Martínez, Marycarmen author Cidad Velasco, María Del Pilar author García Mateo, Nadia author Moreno Estar, Sara author Serna Pérez, Julia author Fernández, Mirella author Swärd, Karl author Simarro Grande, María author Fuente García, Miguel Ángel de la author López López, José Ramón author Pérez García, María Teresa 2019-11-04T09:36:19Z 2019-11-04T09:36:19Z 2019 Arterioscler Thromb Vasc Biol. 2019 Oct 10:ATVBAHA119313492. doi: 10.1161/ATVBAHA.119.313492 1079-5642 http://uvadoc.uva.es/handle/10324/39005 10.1161/ATVBAHA.119.313492 Arteriosclerosis, Thrombosis, and Vascular Biology 1524-4636 Objective: We have previously described that changes in the expression of Kv channels associate to phenotypic modulation (PM), so that Kv1.3 /Kv1.5 ratio is a landmark of vascular smooth muscle cells (VSMCs) phenotype. Moreover, we demonstrated that the Kv1.3 functional expression is relevant for PM in several types of vascular lesions. Here, we explore the efficacy of Kv1.3 inhibition for the prevention of remodeling in human vessels, and the mechanisms linking the switch in Kv1.3 /Kv1.5 ratio to PM. Approach and Results: Vascular remodeling was explored using organ culture and primary cultures of VSMCs obtained from human vessels. We studied the effects of Kv1.3 inhibition on serum-induced remodeling, as well as the impact of viral vector-mediated overexpression of Kv channels or myocardin knock-down. Kv1.3 blockade prevented remodeling by inhibiting proliferation, migration and extracellular matrix (ECM) secretion. PM activated Kv1.3 via downregulation of Kv1.5. Hence, both Kv1.3 blockers and Kv1.5 overexpression inhibited remodeling in a non-additive fashion. Finally, myocardin knock-down induced vessel remodeling and Kv1.5 downregulation and myocardin overexpression increased Kv1.5, while Kv1.5 overexpression inhibited PM without changing myocardin expression. Conclusions: We demonstrate that Kv1.5 channel gene is a myocardin-regulated, VSMCs contractile marker. Kv1.5 downregulation upon PM leaves Kv1.3 as the dominant Kv1 channel expressed in dedifferentiated cells. We demonstrated that the inhibition of Kv1.3 channel function with selective blockers or by preventing Kv1.5 downregulation can represent an effective, novel strategy for the prevention of intimal hyperplasia and restenosis of the human vessels used for coronary angioplasty procedures. spa Myocardin-Dependent Kv1.5 Channel Expression Prevents Phenotypic Modulation of Human Vessels in Organ Culture info:eu-repo/semantics/article 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