Abstract
Arrhythmogenic cardiomyopathy (ACM) is a heart muscle disease associated with ventricular arrhythmias and a high risk of sudden cardiac death (SCD). Although the disease was described over 40 years ago, its diagnosis is still difficult. Several studies have identified a set of five proteins (plakoglobin, Cx43, Nav1.5, SAP97 and GSK3β), which are consistently re-distributed in myocardial samples from ACM patients. Not all protein shifts are specific to ACM, but their combination has provided us with a molecular signature for the disease, which has greatly aided post-mortem diagnosis of SCD victims. The use of this signature, however, was heretofore restricted in living patients, as the analysis requires a heart sample. Recent studies have shown that buccal cells behave similarly to the heart in terms of protein re-localization. Protein shifts are associated with disease onset, deterioration and favorable response to anti-arrhythmic therapy. Accordingly, buccal cells can be used as a surrogate for the myocardium to aid diagnosis, risk stratification and even monitor response to pharmaceutical interventions. Buccal cells can also be kept in culture, hence providing an ex vivo model from the patient, which can offer insights into the mechanisms of disease pathogenesis, including drug response. This review summarizes how the cheek can aid the heart in the battle against ACM.