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Role of Receptor Activator of Nuclear Factor k B Ligand (RANKL) in Coronary Smooth Muscle Contraction and Medial Calcification
Author(s) -
Barnard April,
Noblet Jillian,
Goodwill Adam,
Kiel Alex,
Sturek Joshua,
Tune Johnathan
Publication year - 2017
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.31.1_supplement.1017.18
Subject(s) - rankl , medicine , endocrinology , coronary arteries , vascular smooth muscle , calcification , chemistry , receptor , activator (genetics) , artery , smooth muscle
Recent evidence indicates that coronary perivascular adipose tissue (PVAT) secretes osteogenic factors including receptor activator of nuclear factor k B ligand (RANKL) which may contribute to the initiation and progression of coronary calcification. This study was designed to examine the vascular effects of RANKL on vasomotor function and arterial calcification in ex vivo cultured epicardial coronary arteries from healthy swine. Isolated arterial rings (~3mm length) were cultured with or without RANKL (300 pM) or the RANKL endogenous antagonist osteoprotegrin (OPG; 30 pM) for acute, 2 or 8 days in osteogenic media (DMEM supplemented with 30% fetal bovine serum, 3.8 mM phosphate, 7.5 U/ml alkaline phosphatase). Isometric tension studies of acutely treated arteries demonstrated no effect of RANKL or OPG on coronary arteries contractions to KCl (0 – 60mM) or relaxations to bradykinin (1 nM – 1μM). In contrast, KCl contractions were attenuated ~25% by RANKL incubation for 2 days (P = 0.02) and 8 days of culture (P = 0.002). OPG exposure had no effect on contractile function of cultured rings. Vascular smooth muscle viability following 8 day of culture was verified by concentration‐dependent relaxation to adenosine (10nM – 10μM), which was similar in all treatment groups. Von Kossa staining revealed time dependent increases in medial coronary calcification following 2–8 days of culture with RANKL (P = 0.037). Coronary calcification in arteries exposed to OPG were similar to untreated time controls (P = 0.853). Taken together, these data suggest the potential of RANKL to promote trans‐differentiation and calcification of coronary vascular smooth muscle.