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TRPV4‐associated alterations of Ca 2+ pulsars in a murine model of pulmonary hypertension secondary to heart failure (1090.11)
Author(s) -
Dayeh Nour,
Safar Steven,
Gillis MarcAntoine,
Blanchette Alexandre,
Dupuis Jocelyn,
Ledoux Jonathan
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.1090.11
Subject(s) - pulmonary hypertension , endothelium , intracellular , trpv4 , vasodilation , homeostasis , heart failure , medicine , endocrinology , chemistry , endothelial dysfunction , cardiology , biology , biochemistry , transient receptor potential channel , receptor
Heart failure is the most frequent cause of pulmonary hypertension (PH) (group 2). Pathophysiological mechanisms modulating pulmonary vascular tone and leading to group 2‐PH are poorly defined. Since Ca 2+ homeostasis is crucial to endothelial control of vascular tone, mechanisms involved, including TRPV4 channels, may be altered. This study aimed to characterize intracellular Ca 2+ dynamics in pulmonary endothelium and their alterations in group 2 PH. A mouse model of group 2 PH was developed and 3 rd order resistance arteries were isolated to investigate endothelial intracellular Ca 2+ . TRPV4 involvement was studied using a high‐speed confocal microscope. Characterization of endothelial localized calcium transients, similar to Ca 2+ pulsars, was carried out in pulmonary arteries from control mice. Exposure of Sham arteries to GSK1016790A (100 nM), a TRPV4‐agonist, increased the frequency (1.5 fold) of Ca 2+ pulsars. However, exposure to GSK1016790A had little if any effect on Ca 2+ dynamics in PH arteries. TRPV4 channel expression at both mRNA and protein levels within pulmonary endothelium was confirmed by qPCR, IHC and WB approaches. Our data suggest a potential role for endothelial TRPV4 in vasoregulatory alterations involving local Ca 2+ dynamics. This study strengthens our understanding of endothelial Ca 2+ dyshomeostasis occurring in a clinically relevant model of PH. Grant Funding Source : FRQS, HSFC, FICM, CIHR