Increased Sarcolipin Expression and Adrenergic Drive in Humans With Preserved Left Ventricular Ejection Fraction and Chronic Isolated Mitral Regurgitation

Junying Zheng; Danielle M Yancey; Mustafa I Ahmed; Chih-Chang Wei; Pamela C Powell; Mayilvahanan Shanmugam; Himanshu Gupta; Steven G Lloyd; David C McGiffin; Chun G Schiros; Thomas S Denney; Gopal J Babu; Louis J Dell’Italia

doi:10.1161/CIRCHEARTFAILURE.113.000519

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Increased Sarcolipin Expression and Adrenergic Drive in Humans With Preserved Left Ventricular Ejection Fraction and Chronic Isolated Mitral Regurgitation

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Increased Sarcolipin Expression and Adrenergic Drive in Humans With Preserved Left Ventricular Ejection Fraction and Chronic Isolated Mitral Regurgitation

Junying Zheng, Danielle M Yancey, Mustafa I Ahmed, Chih-Chang Wei, Pamela C Powell, Mayilvahanan Shanmugam, Himanshu Gupta, Steven G Lloyd, David C McGiffin, Chun G Schiros, …

Circulation. Heart failure, Vol.7(1), pp.194-202

01/2014

DOI: https://doi.org/10.1161/CIRCHEARTFAILURE.113.000519

PMCID: PMC3925978

PMID: 24297688

Abstract

Background— There is currently no therapy proven to attenuate left ventricular (LV) dilatation and dysfunction in volume overload induced by isolated mitral regurgitation (MR). To better understand molecular signatures underlying isolated MR, we performed LV gene expression analyses and overlaid regulated genes into ingenuity pathway analysis in patients with isolated MR. Methods and Results— Gene arrays from LV tissue of 35 patients, taken at the time of surgical repair for isolated MR, were compared with 13 normal controls. Cine-MRI was performed in 31 patients before surgery to measure LV function and volume from serial short-axis summation. LV end-diastolic volume was 2-fold ( P =0.005) higher in MR patients than in normal controls, and LV ejection fraction was 64±7% (50%–79%) in MR patients. Ingenuity pathway analysis identified significant activation of pathways involved in β-adrenergic, cAMP, and G-protein–coupled signaling, whereas there was downregulation of pathways associated with complement activation and acute phase response. SERCA2a and phospholamban protein were unchanged in MR versus control left ventricles. However, mRNA and protein levels of the sarcoplasmic reticulum Ca 2+ ATPase (SERCA) regulatory protein sarcolipin, which is predominantly expressed in normal atria, were increased 12- and 6-fold, respectively. Immunofluorescence analysis confirmed the absence of sarcolipin in normal left ventricles and its marked upregulation in MR left ventricles. Conclusions— These results demonstrate alterations in multiple pathways associated with β-adrenergic signaling and sarcolipin in the left ventricles of patients with isolated MR and LV ejection fraction >50%, suggesting a beneficial role for β-adrenergic blockade in isolated MR.

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Title: Increased Sarcolipin Expression and Adrenergic Drive in Humans With Preserved Left Ventricular Ejection Fraction and Chronic Isolated Mitral Regurgitation
Creators: Junying Zheng - From Birmingham Veteran Affairs Medical Center (C.C.W., H.G., S.G.L., L.J.D.), Department of Medicine, Division of Cardiovascular Disease (J.Z., D.M.Y., M.I.A., C.C.W., P.C.P., H.G., S.G.L., L.J.D.), and Division of Cardiovascular Surgery (D.C.M.), University of Alabama at Birmingham; Department of Electrical and Computer Engineering, Auburn University, AL (C.G.S., T.S.D.); and Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey–NJMS, Newark (M.S., G
Danielle M Yancey - From Birmingham Veteran Affairs Medical Center (C.C.W., H.G., S.G.L., L.J.D.), Department of Medicine, Division of Cardiovascular Disease (J.Z., D.M.Y., M.I.A., C.C.W., P.C.P., H.G., S.G.L., L.J.D.), and Division of Cardiovascular Surgery (D.C.M.), University of Alabama at Birmingham; Department of Electrical and Computer Engineering, Auburn University, AL (C.G.S., T.S.D.); and Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey–NJMS, Newark (M.S., G
Mustafa I Ahmed - From Birmingham Veteran Affairs Medical Center (C.C.W., H.G., S.G.L., L.J.D.), Department of Medicine, Division of Cardiovascular Disease (J.Z., D.M.Y., M.I.A., C.C.W., P.C.P., H.G., S.G.L., L.J.D.), and Division of Cardiovascular Surgery (D.C.M.), University of Alabama at Birmingham; Department of Electrical and Computer Engineering, Auburn University, AL (C.G.S., T.S.D.); and Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey–NJMS, Newark (M.S., G
Chih-Chang Wei - From Birmingham Veteran Affairs Medical Center (C.C.W., H.G., S.G.L., L.J.D.), Department of Medicine, Division of Cardiovascular Disease (J.Z., D.M.Y., M.I.A., C.C.W., P.C.P., H.G., S.G.L., L.J.D.), and Division of Cardiovascular Surgery (D.C.M.), University of Alabama at Birmingham; Department of Electrical and Computer Engineering, Auburn University, AL (C.G.S., T.S.D.); and Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey–NJMS, Newark (M.S., G
Pamela C Powell - From Birmingham Veteran Affairs Medical Center (C.C.W., H.G., S.G.L., L.J.D.), Department of Medicine, Division of Cardiovascular Disease (J.Z., D.M.Y., M.I.A., C.C.W., P.C.P., H.G., S.G.L., L.J.D.), and Division of Cardiovascular Surgery (D.C.M.), University of Alabama at Birmingham; Department of Electrical and Computer Engineering, Auburn University, AL (C.G.S., T.S.D.); and Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey–NJMS, Newark (M.S., G
Mayilvahanan Shanmugam - From Birmingham Veteran Affairs Medical Center (C.C.W., H.G., S.G.L., L.J.D.), Department of Medicine, Division of Cardiovascular Disease (J.Z., D.M.Y., M.I.A., C.C.W., P.C.P., H.G., S.G.L., L.J.D.), and Division of Cardiovascular Surgery (D.C.M.), University of Alabama at Birmingham; Department of Electrical and Computer Engineering, Auburn University, AL (C.G.S., T.S.D.); and Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey–NJMS, Newark (M.S., G
Himanshu Gupta - From Birmingham Veteran Affairs Medical Center (C.C.W., H.G., S.G.L., L.J.D.), Department of Medicine, Division of Cardiovascular Disease (J.Z., D.M.Y., M.I.A., C.C.W., P.C.P., H.G., S.G.L., L.J.D.), and Division of Cardiovascular Surgery (D.C.M.), University of Alabama at Birmingham; Department of Electrical and Computer Engineering, Auburn University, AL (C.G.S., T.S.D.); and Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey–NJMS, Newark (M.S., G
Steven G Lloyd - From Birmingham Veteran Affairs Medical Center (C.C.W., H.G., S.G.L., L.J.D.), Department of Medicine, Division of Cardiovascular Disease (J.Z., D.M.Y., M.I.A., C.C.W., P.C.P., H.G., S.G.L., L.J.D.), and Division of Cardiovascular Surgery (D.C.M.), University of Alabama at Birmingham; Department of Electrical and Computer Engineering, Auburn University, AL (C.G.S., T.S.D.); and Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey–NJMS, Newark (M.S., G
David C McGiffin - From Birmingham Veteran Affairs Medical Center (C.C.W., H.G., S.G.L., L.J.D.), Department of Medicine, Division of Cardiovascular Disease (J.Z., D.M.Y., M.I.A., C.C.W., P.C.P., H.G., S.G.L., L.J.D.), and Division of Cardiovascular Surgery (D.C.M.), University of Alabama at Birmingham; Department of Electrical and Computer Engineering, Auburn University, AL (C.G.S., T.S.D.); and Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey–NJMS, Newark (M.S., G
Chun G Schiros - From Birmingham Veteran Affairs Medical Center (C.C.W., H.G., S.G.L., L.J.D.), Department of Medicine, Division of Cardiovascular Disease (J.Z., D.M.Y., M.I.A., C.C.W., P.C.P., H.G., S.G.L., L.J.D.), and Division of Cardiovascular Surgery (D.C.M.), University of Alabama at Birmingham; Department of Electrical and Computer Engineering, Auburn University, AL (C.G.S., T.S.D.); and Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey–NJMS, Newark (M.S., G
Thomas S Denney - From Birmingham Veteran Affairs Medical Center (C.C.W., H.G., S.G.L., L.J.D.), Department of Medicine, Division of Cardiovascular Disease (J.Z., D.M.Y., M.I.A., C.C.W., P.C.P., H.G., S.G.L., L.J.D.), and Division of Cardiovascular Surgery (D.C.M.), University of Alabama at Birmingham; Department of Electrical and Computer Engineering, Auburn University, AL (C.G.S., T.S.D.); and Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey–NJMS, Newark (M.S., G
Gopal J Babu - From Birmingham Veteran Affairs Medical Center (C.C.W., H.G., S.G.L., L.J.D.), Department of Medicine, Division of Cardiovascular Disease (J.Z., D.M.Y., M.I.A., C.C.W., P.C.P., H.G., S.G.L., L.J.D.), and Division of Cardiovascular Surgery (D.C.M.), University of Alabama at Birmingham; Department of Electrical and Computer Engineering, Auburn University, AL (C.G.S., T.S.D.); and Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey–NJMS, Newark (M.S., G
Louis J Dell’Italia - From Birmingham Veteran Affairs Medical Center (C.C.W., H.G., S.G.L., L.J.D.), Department of Medicine, Division of Cardiovascular Disease (J.Z., D.M.Y., M.I.A., C.C.W., P.C.P., H.G., S.G.L., L.J.D.), and Division of Cardiovascular Surgery (D.C.M.), University of Alabama at Birmingham; Department of Electrical and Computer Engineering, Auburn University, AL (C.G.S., T.S.D.); and Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey–NJMS, Newark (M.S., G
Publication Details: Circulation. Heart failure, Vol.7(1), pp.194-202
Date published: 01/2014
Academic Unit: Cell Biology and Molecular Medicine (NJMS)
Language: English
Resource Type: Journal article
Identifiers: 991031666122704646