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Myocardin-Dependent...
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Arévalo-Martínez, MarycarmenUniversity of Valladolid
(författare)
Myocardin-Dependent Kv1.5 Channel Expression Prevents Phenotypic Modulation of Human Vessels in Organ Culture
- Artikel/kapitelEngelska2019
Förlag, utgivningsår, omfång ...
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:2993d507-192c-4c34-8fd6-0eee146fa6b0
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https://lup.lub.lu.se/record/2993d507-192c-4c34-8fd6-0eee146fa6b0URI
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https://doi.org/10.1161/ATVBAHA.119.313492DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
Anmärkningar
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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 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 vascular smooth muscle cells 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 secretion. PM activated Kv1.3 via downregulation of Kv1.5. Hence, both Kv1.3 blockers and Kv1.5 overexpression inhibited remodeling in a nonadditive 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, vascular smooth muscle cells 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.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Cidad, PilarUniversity of Valladolid
(författare)
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García-Mateo, NadiaUniversity of Valladolid
(författare)
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Moreno-Estar, SaraUniversity of Valladolid
(författare)
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Serna, JuliaUniversity of Valladolid
(författare)
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Fernández, MirellaUniversity of Valladolid
(författare)
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Swärd, KarlLund University,Lunds universitet,Cellulär biomekanik,Forskargrupper vid Lunds universitet,Cellular Biomechanics,Lund University Research Groups(Swepub:lu)mphy-ksw
(författare)
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Simarro, MaríaUniversity of Valladolid
(författare)
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de la Fuente, Miguel A.University of Valladolid
(författare)
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López-López, José R.University of Valladolid
(författare)
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Pérez-García, M. TeresaUniversity of Valladolid
(författare)
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University of ValladolidCellulär biomekanik
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Arteriosclerosis, Thrombosis, and Vascular Biology39:12, s. 273-2861524-4636
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Till lärosätets databas
- Av författaren/redakt...
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Arévalo-Martínez ...
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Cidad, Pilar
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García-Mateo, Na ...
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Moreno-Estar, Sa ...
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Serna, Julia
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Fernández, Mirel ...
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visa fler...
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Swärd, Karl
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Simarro, María
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de la Fuente, Mi ...
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López-López, Jos ...
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Pérez-García, M. ...
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Cell och molekyl ...
- Artiklar i publikationen
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Arteriosclerosis ...
- Av lärosätet
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Lunds universitet