TY - JOUR
T1 - Effects of adiponectin on calcium-handling proteins in heart failure with preserved ejection fraction
AU - Tanaka, Komei
AU - Wilson, Richard M.
AU - Essick, Eric E.
AU - Duffen, Jennifer L.
AU - Scherer, Philipp E.
AU - Ouchi, Noriyuki
AU - Sam, Flora
N1 - Publisher Copyright:
© 2014 American Heart Association, Inc.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - Background-Despite the increasing prevalence of heart failure with preserved ejection fraction (HFpEF) in humans, there remains no therapeutic options for HFpEF. Adiponectin, an adipocyte-derived cytokine, exerts cardioprotective actions, and its deficiency is implicated in the development of hypertension and HF with reduced ejection fraction. Similarly, adiponectin deficiency in HFpEF exacerbates left ventricular hypertrophy, diastolic dysfunction, and HF. However, the therapeutic effects of adiponectin in HFpEF remain unknown. We sought to test the hypothesis that chronic adiponectin overexpression protects against the progression of HF in a murine model of HFpEF. Methods and Results-Adiponectin transgenic and wild-type mice underwent uninephrectomy, a continuous saline or daldosterone infusion and given 1.0% sodium chloride drinking water for 4 weeks. Aldosterone-infused wild-type mice developed HFpEF with hypertension, left ventricular hypertrophy, and diastolic dysfunction. Aldosterone infusion increased myocardial oxidative stress and decreased sarcoplasmic reticulum Ca2+-ATPase protein expression in HFpEF. Although total phospholamban protein expression was unchanged, there was a decreased expression of protein kinase A-dependent phospholamban phosphorylation at Ser16 and CaMKII (Ca2+/calmodulin-dependent protein kinase II)-dependent phospholamban phosphorylation at Thr17. Adiponectin overexpression in aldosterone-infused mice ameliorated left ventricular hypertrophy, diastolic dysfunction, lung congestion, and myocardial oxidative stress without affecting blood pressure and left ventricular EF. This improvement in diastolic dysfunction parameters in aldosteroneinfused adiponectin transgenic mice was accompanied by the preserved protein expression of protein kinase A-dependent phosphorylation of phospholamban at Ser16. Adiponectin replacement prevented the progression of aldosterone-induced HFpEF, independent of blood pressure, by improving diastolic dysfunction and by modulating cardiac hypertrophy. Conclusions-These findings suggest that adiponectin may have therapeutic effects in patients with HFpEF.
AB - Background-Despite the increasing prevalence of heart failure with preserved ejection fraction (HFpEF) in humans, there remains no therapeutic options for HFpEF. Adiponectin, an adipocyte-derived cytokine, exerts cardioprotective actions, and its deficiency is implicated in the development of hypertension and HF with reduced ejection fraction. Similarly, adiponectin deficiency in HFpEF exacerbates left ventricular hypertrophy, diastolic dysfunction, and HF. However, the therapeutic effects of adiponectin in HFpEF remain unknown. We sought to test the hypothesis that chronic adiponectin overexpression protects against the progression of HF in a murine model of HFpEF. Methods and Results-Adiponectin transgenic and wild-type mice underwent uninephrectomy, a continuous saline or daldosterone infusion and given 1.0% sodium chloride drinking water for 4 weeks. Aldosterone-infused wild-type mice developed HFpEF with hypertension, left ventricular hypertrophy, and diastolic dysfunction. Aldosterone infusion increased myocardial oxidative stress and decreased sarcoplasmic reticulum Ca2+-ATPase protein expression in HFpEF. Although total phospholamban protein expression was unchanged, there was a decreased expression of protein kinase A-dependent phospholamban phosphorylation at Ser16 and CaMKII (Ca2+/calmodulin-dependent protein kinase II)-dependent phospholamban phosphorylation at Thr17. Adiponectin overexpression in aldosterone-infused mice ameliorated left ventricular hypertrophy, diastolic dysfunction, lung congestion, and myocardial oxidative stress without affecting blood pressure and left ventricular EF. This improvement in diastolic dysfunction parameters in aldosteroneinfused adiponectin transgenic mice was accompanied by the preserved protein expression of protein kinase A-dependent phosphorylation of phospholamban at Ser16. Adiponectin replacement prevented the progression of aldosterone-induced HFpEF, independent of blood pressure, by improving diastolic dysfunction and by modulating cardiac hypertrophy. Conclusions-These findings suggest that adiponectin may have therapeutic effects in patients with HFpEF.
KW - Adiponectin
KW - Calcium-binding proteins
KW - Diastolic
KW - Heart failure
KW - Hypertrophy
KW - Left ventricular
KW - Oxidative stress
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U2 - 10.1161/CIRCHEARTFAILURE.114.001279
DO - 10.1161/CIRCHEARTFAILURE.114.001279
M3 - Article
C2 - 25149095
AN - SCOPUS:84925780303
SN - 1941-3289
VL - 7
SP - 976
EP - 985
JO - Circulation: Heart Failure
JF - Circulation: Heart Failure
IS - 6
ER -