Left ventricular non-compaction is associated with lateral disconnection of cardiomyocytes and down-regulation of Ephrin-B1

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Abstract Background Ephrin-B1 (Ep) is a major component of lateral junctions (LJ) of cardiomyocytes conferring cell-cell essential mechanical and electrical interactions. We investigated the structure of LJ as well as Ep expression in human left ventricular non-compaction (LVNC). Materials and Methods left ventricular endomyocardial biopsies (LVEMB) from 13 patients with LVNC (M 8; F 5 mean age 48± 12.8) recognized by cardiac magnetic resonance (LV non-compaction/compaction ratio> 2.3) and LV angiography (intramural channels arising from endocardium), with reduced contractility (LVEF<50%) in 6 cases, were processed for histology, electron-microscopy, PCR for the most common viral genomes and western blot assessment of Ep. Results At histology, intramural channels arising from endocardium were partially or completely unendotheliolized and showed platelet activation up to formation of organized thrombi. Cardiomyocytes diffusely showed various degree of disconnection up to complete detachment. At electron microscopy myocyte disconnection was systematically identified at lateral junction with preserved structure of intercalated disk. Overlapping virus negative lymphocytic myocarditis was observed in 6 out of 13 (46%) of patients with LVNC. Western blot evaluation of Ep was 3.4-fold lower than controls (6229±3197 vs 21451±5054 arbitrary units), p=0.2187. (p<0.001) Conclusions LVNC is associated with lateral disconnection of cardiomyocytes and down-regulation of Ep. Overlapping virus-negative myocarditis is detectable in up to 46% of cases. Figure legend Panels A and B represent CMR images showing extensive intramural channels denoting LVNC. Panel C: histological section in H&E (200 X) of a LV endomyocardial biopsy from a patient affected by LVNC showing diffuse cardiomyocytes’ disconnection with formation of large intramural channels. Panel D: Electron microscopy of a LV endomyocardial biopsy from a patient with LVNC indicating a lateral detachment of cardiomyocytes which surface is completely unendotheliolized. Panels E-F: Immunofluorescence for Ep demonstrating its remarkable down-regulation in a LV biopsy from a LVNC subject (panel E) compared with normal control (panel F).Panels G-H: Western blot quantification of Ep in the myocardium of 13 patients with LVNC (panel G) indicating a 3.4 fold reduction of Ep expression in LVNC pts vs normal controls (panel H) Alpha-sarcomeric actin (45 Kd) was used as control.

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