Enhanced store-operated Ca2+ influx and ORAI1 expression in ventricular fibroblasts from human failing heart

• Published in: Biology open 2017-03, Vol.6 (3), p.326-332
• Main Authors: Ross, Gracious R., Bajwa, Tanvir, Edwards, Stacie, Emelyanova, Larisa, Rizvi, Farhan, Holmuhamedov, Ekhson L., Werner, Paul, Downey, Francis X., Tajik, A. Jamil, Jahangir, Arshad
• Format: Article
• Language: English
• Subjects: Calcium; Calcium (intracellular); Calcium channels; Calcium imaging; Calcium influx; Calcium ions; Calcium signalling; Cardiac fibrosis; Cell culture; Channels; Collagen; Collagen (type I); Congestive heart failure; Correlation coefficient; Correlation coefficients; Deposition; Extracellular matrix; Fibroblasts; Fibrosis; Fluo-3; Heart; Heart diseases; Heart failure; Histology; Immunoblotting; Incubation; Intracellular; Localization; Orai1 protein; Polymerase chain reaction; Pore formation; STIM1 protein; Store-operated Ca2+ entry; Thapsigargin; Ventricle
• ISSN: 2046-6390; 2046-6390
• DOI: 10.1242/bio.022632

Excessive cardiac fibrosis, characterized by increased collagen-rich extracellular matrix (ECM) deposition, is a major predisposing factor for mechanical and electrical dysfunction in heart failure (HF). The human ventricular fibroblast (hVF) remodeling mechanisms that cause excessive collagen deposition in HF are unclear, although reports suggest a role for [Ca2+]i in fibrosis. Therefore, we determined the association of differences in cellular Ca2+ dynamics and collagen secretion/deposition between hVFs from failing and normal (control) hearts. Histology of left ventricle sections (Masson trichrome) confirmed excessive fibrosis in HF vs normal. In vitro, hVFs from HF showed increased secretion/deposition of soluble collagen in 48 hours of culture compared with control [85.9±7.4 μg/106 vs 58.5±8.8 μg/106 cells, P