Inflammation in Cardiomyopathies: Cellular Mechanisms Across Cardiac Phenotype.

Area of Science:

• Cardiovascular Medicine
• Immunology
• Pathophysiology

Background:

• Cardiomyopathies are traditionally classified by structural and genetic factors.
• Emerging evidence indicates chronic myocardial inflammation is a key driver of disease progression across various cardiomyopathies.
• This review focuses on the shared inflammatory mechanisms in hypertrophic cardiomyopathy, Anderson-Fabry disease, cardiac amyloidosis, arrhythmogenic cardiomyopathy, and dilated cardiomyopathy.

Purpose of the Study:

• To synthesize current literature on cellular and molecular inflammatory mechanisms in distinct cardiomyopathies.
• To identify common endogenous triggers and immune pathways involved in cardiomyopathy pathogenesis.
• To explore the potential of immunomodulatory therapies for treating cardiomyopathies.

Main Methods:

• Literature review of cellular and molecular inflammatory mechanisms in cardiomyopathies.
• Analysis of endogenous triggers acting as damage-associated molecular patterns.
• Examination of innate and adaptive immune cascades, including Toll-like receptors, NF-κB, and NLRP3 inflammasome.

Main Results:

• Common endogenous triggers (metabolic substrates, amyloid fibrils, mechanical stress, viral genomes) activate immune responses.
• Activation of Toll-like receptors, NF-κB, and NLRP3 inflammasome creates a pro-inflammatory microenvironment.
• This inflammation promotes fibroblast reprogramming, myocardial edema, and fibrotic remodeling, contributing to disease progression.

Conclusions:

• Inflammation is a central pathophysiological mechanism in cardiomyopathies, not merely a secondary bystander.
• Shared immune pathways provide a framework for improved risk stratification.
• Targeted immunomodulatory therapies hold potential for altering disease trajectories in cardiomyopathies.