Premium
Age‐related Changes in Endothelial Ca 2+ Signaling Revealed by Imaging from Inside Arteries at Normal Physiological Pressures
Author(s) -
Wilson Calum,
Saunter Christopher,
Girkin John,
McCarron John
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.553.10
Subject(s) - endothelium , acetylcholine , electrical impedance myography , chemistry , calcium signaling , endothelial dysfunction , lumen (anatomy) , calcium , calcium in biology , endocrinology , endothelial stem cell , medicine , biophysics , vasodilation , intracellular , biology , biochemistry , in vitro
Aging is the summation of many, mostly invisible, but deleterious changes associated with altered structure and function of the cardiovascular system. Age‐induced impairment of endothelial function contributes to and reinforces the changes that occur in vascular disease. Normally, the endothelium transduces multiple chemical and mechanical signals into changes in cytoplasmic calcium (Ca 2+ ) concentration that control vascular function. Thus, understanding age‐related functional changes in the endothelium requires an appreciation of Ca 2+ control. We developed a wide‐field, gradient‐index (GRIN) fluorescence imaging system to visualize the endothelium from within the lumen of intact, pressurized arteries. The GRIN system enables rapid imaging of a 500 μm diameter area of the curved endothelial surface (~200 endothelial cells; ECs) with subcellular resolution. We also developed a semi‐automated data extraction procedure to quantify signal dynamics in the individual ECs loaded with fluorescent Ca 2+ indicators. In the carotid artery of young rats (3 months), acetylcholine (ACh) evoked endothelial Ca 2+ signals that were suppressed as intraluminal pressure increased. In aged rats (18 months) the pressure‐dependent suppression of ACh‐evoked Ca 2+ signaling and the frequency of ACh‐evoked intracellular Ca 2+ oscillations were reduced, whilst the temporal propagation of Ca 2+ signals increased. Significantly, dose response measurements revealed that aging increased EC sensitivity to ACh, yet had no effect on the magnitude of the Ca 2+ response in each cell. We propose that such alterations in EC Ca 2+ signaling may manifest as a loss of functionality, and explain endothelial dysfunction in aging.