Data from: Layer-specific proteomic analysis of human hearts in patients with sudden cardiac death

Recent studies have shown that decreased longitudinal strain in
speckle-tracking echography can predict sudden cardiac death (SCD) in
patients with cardiac hypertrophy (CH). Histologically, the heart wall
consists of the inner longitudinal, middle circular, and outer
longitudinal layers. Thus, layer-specific proteomic changes may contribute
to SCD risk. The three layers in human cardiac tissues were obtained
during autopsies of SCD, compensated CH, and control cases (18 cases aged
> 40 years, 54 samples in total). SCD cases consisted of patients
with ischemic or hypertensive heart failure, whereas CH and control cases
were accidental deaths. After histological analysis, cardiomyocytes were
collected separately from the three layers of the left ventricular wall
using laser microdissection. The extracted proteins were analyzed using
liquid chromatography–tandem mass spectrometry, followed by label-free
quantification. Histologically, cardiomyocytes were enlarged in all layers
of SCD and CH cases without significant progression of myocardial
fibrosis. The proteomic profiles of SCD and CH cases were distinguishable
from those of control cases, especially in the inner layer. The levels of
mitochondrial and calcium-handling proteins were significantly decreased
in SCD hearts. Arrhythmogenic changes, including decreased PKP2 and RYR2
levels, developed in a stepwise manner from control through CH to SCD,
most prominently in the inner layer. Immunohistochemical analysis showed
reduced levels of PKP2 in intercalated disks and RYR2 in sarcomeres.
Because proteomic alterations precede the progression of myocardial
fibrosis, their detection may enhance the accuracy of postmortem diagnosis
of SCD in middle-aged and older asymptomatic individuals with CH.