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. Author manuscript; available in PMC: 2021 May 5.
Published in final edited form as: Circulation. 2020 Mar 3;141(18):1477–1493. doi: 10.1161/CIRCULATIONAHA.119.043504

Figure 1. Left ventricular tissue from ARVC patients is characterized by integrin β1D down-regulation and RyR2 Ser-2030 hyper-phosphorylation.

Figure 1.

(A) Representative ECG recordings from four patients with ARVC obtained during hospitalization but before cardiac transplantation. (B) Quantification of proteins associated with intracellular calcium release from the sarcoplasmic reticulum from protein mass spectrometry analyses. (C) Representative immunofluorescence images obtained using antiserum against integrin β1D in fixed left ventricle tissue sections from healthy donor (HD, left) or ARVC patients (right). (D) Quantification of integrin β1D Immunofluorescence intensity (n=4 per group; Each group includes 5 slides). (E) Representative immunoblots for integrin β1D, total RyR2, pRyR2 Ser-2808, pRyR2 Ser-2814, pRyR2 Ser-2030 and GAPDH protein expression in left ventricular tissue homogenates from HDs or patients with ARVC. (F) Quantification of integrin β1D immunoblots shown in (E) relative to GAPDH expression (n=4 per group). Note that both mature and precursor forms of β1D integrin subunit were reduced. (G-I) Quantification of immunoblots showing increased phosphorylation of RyR2 at Ser-2030 in left ventricle tissue from patients with ARVC compared to HD tissue HD. There were no significant differences between the groups in RyR2 phosphorylation at Ser-2808 or Ser-2814. (n=4 per group). The data represent the means ± SEM; *P<0.05; ***P<0.001; n.s., not significant; Student’s t test. Abbreviations: ARVC, Arrhythmogenic right ventricular cardiomyopathy; HD, Healthy Donors; β1D, integrin β1D; RyR2, Ryanodine Receptor 2; BIN1, Bridging integrator 1; Cav1.2, L-type Cav1.2 calcium channel; CaM, Calmodulin; CASQ2, Calsequestrin 2; IP3R2; Inositol 1,4,5-trisphosphate receptor, type 2; ITGB1, Integrin beta-1; JCTN, Junctin; JP2, Junctophilin-2; NCX1, Na+/Ca2+ exchanger, isoform 1; PLB, phospholamban; SERCA2a; Sarcoplasmic / endoplasmic reticulum Ca2+ ATPase 2a; TRDN, Triadin; GAPDH, glyceraldehyde 3-phosphate dehydrogenase.