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Changes in vascular reactivity and endothelial Ca 2+ dynamics with chronic low flow
Author(s) -
Taylor Mark S.,
Choi Chungsik,
Bayazid Leith,
Glosemeyer Katherine E.,
Baker Calvin C. P.,
Weber David S.
Publication year - 2017
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/micc.12354
Subject(s) - neointima , endothelium , endothelial dysfunction , vasodilation , medicine , cardiology , chemistry , anatomy , restenosis , stent
Disruption of blood flow promotes endothelial dysfunction and predisposes vessels to remodeling and atherosclerosis. Recent findings suggest that spatial and temporal tuning of local Ca 2+ signals along the endothelium is vital to vascular function. In this study, we examined whether chronic flow disruption causes alteration of dynamic endothelial Ca 2+ signal patterning associated with changes in vascular structure and function. For these studies, we performed surgical PL of the left carotid arteries of mice to establish chronic low flow for 2 weeks; right carotid arteries remained open and served as controls (C). Histological sections showed substantial remodeling of PL compared to C arteries, including formation of neointima. Isometric force measurements revealed increased PE ‐induced contractions and decreased KC l‐induced contractions in PL vs C arteries. Endothelium‐dependent vasorelaxation in response to AC h; 10 −8 to 10 −5 mol/L) was significantly impaired in PL vs C vessels. Evaluation of endothelial Ca 2+ using confocal imaging and custom analysis exposed distinct impairment of Ca 2+ dynamics in PL arteries, characterized by reduction in active sites and truncation of events, corresponding to attenuated vasorelaxation. Our findings suggest that endothelial dysfunction in developing vascular disease may be characterized by distinct shifts in the spatial and temporal patterns of localized Ca 2+ signals.