Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2166089 | Cell Calcium | 2013 | 11 Pages |
Abstract
Vascular smooth muscle cells undergo phenotypic switches after damage which may contribute to proliferative disorders of the vessel wall. This process has been related to remodeling of Ca2+ channels. We have tested the ability of cultured human coronary artery smooth muscle cells (hCASMCs) to return from a proliferative to a quiescent behavior and the contribution of intracellular Ca2+ remodeling to the process. We found that cultured, early passage hCASMCs showed a high proliferation rate, sustained increases in cytosolic [Ca2+] in response to angiotensin II, residual voltage-operated Ca2+ entry, increased Stim1 and enhanced store-operated currents. Non-steroidal anti-inflammatory drugs inhibited store-operated Ca2+ entry and abolished cell proliferation in a mitochondria-dependent manner. After a few passages, hCASMCs turned to a quiescent phenotype characterized by lack of proliferation, oscillatory Ca2+ response to angiotensin II, increased Ca2+ store content, enhanced voltage-operated Ca2+ entry and Cav1.2 expression, and decreases in Stim1, store-operated current and store-operated Ca2+ entry. We conclude that proliferating hCASMCs return to quiescence and this switch is associated to a remodeling of Ca2+ channels and their control by subcellular organelles, thus providing a window of opportunity for targeting phenotype-specific Ca2+ channels involved in proliferation.
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Authors
Eva Muñoz, Miriam Hernández-Morales, Diego Sobradillo, Asunción Rocher, LucÃa Núñez, Carlos Villalobos,