TY - JOUR
T1 - Glycation of ryanodine receptor in circulating lymphocytes predicts the response to cardiac resynchronization therapy
AU - Gambardella, Jessica
AU - Jankauskas, Stanislovas S.
AU - D'Ascia, Salvatore Luca
AU - Sardu, Celestino
AU - Matarese, Alessandro
AU - Minicucci, Fabio
AU - Mone, Pasquale
AU - Santulli, Gaetano
N1 - Funding Information:
The Santulli's Lab is supported in part by the National Institutes of Health (NIH: R01-HL146691, R01-DK033823, R01-HL159062, R01-DK123259, R56-AG066431, T32-HL144456, and R00-DK107895, to G.S.), by the Diabetes Action Research and Education Foundation (to G.S.), by the Irma T. Hirschl and Monique Weill-Caulier Trusts (to G.S.), and by the American Heart Association (AHA-20POST35211151 to J.G. and AHA-21POST836407 to S.S.J.).
Publisher Copyright:
© 2021 International Society for Heart and Lung Transplantation
PY - 2022/4
Y1 - 2022/4
N2 - Finding reliable parameters to identify patients with heart failure (HF) that will respond to cardiac resynchronization therapy (CRT) represents a major challenge. We and others have observed post-translational modifications of Ryanodine Receptor (RyR) in several tissues (including skeletal muscle and circulating lymphocytes) of patients with advanced HF. We designed a prospective study to test the hypothesis that RyR1 glycation in circulating lymphocytes could predict CRT responsiveness in patients with non-ischemic HF. We enrolled 94 patients who underwent CRT and 30 individuals without HF, examining RyR1 glycation in peripheral lymphocytes at enrollment and after 1 year. We found that baseline RyR1 glycation independently predicts CRT response at 1 year after adjusting for age, diabetes, QRS duration and morphology, echocardiographic dyssynchrony, and hypertension. Moreover, RyR1 glycation in circulating lymphocytes significantly correlated with pathologic intracellular calcium leak. Taken together, our data show for the first time that RyR1 glycation in circulating lymphocytes represents a novel biomarker to predict CRT responsiveness.
AB - Finding reliable parameters to identify patients with heart failure (HF) that will respond to cardiac resynchronization therapy (CRT) represents a major challenge. We and others have observed post-translational modifications of Ryanodine Receptor (RyR) in several tissues (including skeletal muscle and circulating lymphocytes) of patients with advanced HF. We designed a prospective study to test the hypothesis that RyR1 glycation in circulating lymphocytes could predict CRT responsiveness in patients with non-ischemic HF. We enrolled 94 patients who underwent CRT and 30 individuals without HF, examining RyR1 glycation in peripheral lymphocytes at enrollment and after 1 year. We found that baseline RyR1 glycation independently predicts CRT response at 1 year after adjusting for age, diabetes, QRS duration and morphology, echocardiographic dyssynchrony, and hypertension. Moreover, RyR1 glycation in circulating lymphocytes significantly correlated with pathologic intracellular calcium leak. Taken together, our data show for the first time that RyR1 glycation in circulating lymphocytes represents a novel biomarker to predict CRT responsiveness.
KW - CRT
KW - RyR
KW - glycosylation
KW - heart failure
KW - post-translational modifications
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U2 - 10.1016/j.healun.2021.12.008
DO - 10.1016/j.healun.2021.12.008
M3 - Article
C2 - 35042640
AN - SCOPUS:85122969791
SN - 1053-2498
VL - 41
SP - 438
EP - 441
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
IS - 4
ER -
