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Significance of store operated calcium entry in human abdominal aortic aneurysm vascular smooth muscle cells (1057.3)
Author(s) -
Bailey Marc,
Young Richard,
Rode Baptiste,
Foster Richard,
Li Jing,
Beech David
Publication year - 2014
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.28.1_supplement.1057.3
Subject(s) - vascular smooth muscle , thapsigargin , abdominal aortic aneurysm , orai1 , microbiology and biotechnology , medicine , stim1 , endocrinology , biology , calcium , aneurysm , smooth muscle , surgery
Abdominal aortic aneurysm (AAA) is a focal dilatation of the abdominal aorta associated with defective vascular smooth muscle cell (VSMC) function. Store operated calcium entry (SOCE) through Orai1 can modulate cell behaviour. We investigate if SOCE is present in AAA VSMC and if pharmacological blockade impacts cellular behaviour. Methods VMSC were cultured from human AAA and internal mammary artery (IMA). Gene expression was studied by real‐time PCR, calcium imaging using fura‐2AM in response to thapsigargin or platelet derived growth factor (PDGF) and functional assays (proliferation, migration, apoptosis) by time‐lapse fluorescent microscopy. The SOCE inhibitor S66 and its novel analogue JPIII were compared to vehicle control (dimethylsulfoxide).Student t‐test was used to compare responses. Results Orai1/STIM1 mRNA was detected in both cell populations and a SOCE response observed, which was inhibited by S66 or JPIII. The proportion of signal blocked was greater in the AAA VSMC than the IMA VSMC after PDGF stimulation. In functional experiments, treatment of the AAA VSMC with JPIII had no effect on proliferation or migration but conferred protection against apoptosis, which was itself increased in the AAA compared to the IMA VSMC. Conclusion SOCE is functional in AAA VSMC and inhibition protects against apoptosis. The channels warrant further study as a potential therapeutic avenue for AAA. Grant Funding Source : Supported by the British Heart Foundation