Cheek-Pro-Heart: What Can the Buccal Mucosa Do for Arrhythmogenic Cardiomyopathy?

Area of Science:

• Cardiology
• Molecular Biology
• Genetics

Background:

• Arrhythmogenic cardiomyopathy (ACM) is a serious heart muscle disease linked to ventricular arrhythmias and sudden cardiac death (SCD).
• Diagnosing ACM remains challenging, despite over 40 years of research.
• A specific set of five proteins (plakoglobin, Cx43, Nav1.5, SAP97, GSK3β) shows altered distribution in ACM myocardial samples, forming a diagnostic signature.

Purpose of the Study:

• To review the potential of using buccal cells as a surrogate for myocardial tissue in diagnosing and managing ACM.
• To explore how protein re-localization in buccal cells can aid in early diagnosis, risk stratification, and monitoring therapeutic responses in ACM patients.
• To highlight the utility of cultured buccal cells as an ex vivo model for studying ACM pathogenesis and drug responses.

Main Methods:

• Analysis of protein re-distribution patterns in myocardial samples from ACM patients.
• Investigation of protein re-localization in buccal cells as a parallel to cardiac changes.
• Review of studies examining the correlation between protein shifts, disease progression, and treatment efficacy.

Main Results:

• A molecular signature comprising five key proteins aids in post-mortem SCD diagnosis.
• Buccal cells exhibit similar protein re-localization patterns to heart muscle in ACM patients.
• Protein shifts in buccal cells correlate with disease onset, progression, and response to anti-arrhythmic therapy.

Conclusions:

• Buccal cells offer a viable, less invasive alternative to myocardial biopsies for ACM diagnosis and patient management.
• The analysis of buccal cell protein signatures can facilitate diagnosis, risk stratification, and monitoring of treatment effectiveness in living ACM patients.
• Cultured buccal cells provide a valuable ex vivo platform for understanding ACM mechanisms and personalized medicine approaches.