Language
English
Publication Date
10-12-2025
Journal
International Journal of Molecular Sciences
DOI
10.3390/ijms26209931
PMID
41155225
PMCID
PMC12563235
PubMedCentral® Posted Date
10-12-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Cardiac inflammation and hypertrophy develop as a pathologic response to an array of insults, such as myocardial infarctions, chronic systemic hypertension, and valvular defects. Due to the high prevalence of such conditions, there is an increasing need to prevent and halt cardiac hypertrophy. Because cardiac damage and subsequent remodeling can lead to arrhythmias, heart failure, and even sudden cardiac death, inhibition of cardiac hypertrophy is key to reducing cardiovascular-related mortality. The immune system is the driving force behind inflammatory reactions. All three pathways of complement system activation-classical, lectin, and alternative-are implicated in developing cardiac damage, inflammation, and hypertrophy due to infectious and non-infectious causes, autoimmune diseases, genetic polymorphisms, and forms of complement dysregulation. Of interest in this review is the role of the complement system, a collection of soluble and membrane-bound proteins that mediate inflammatory processes through interactions with signaling molecules and immune cells. This review comprehensively discusses the roles of these complement pathways in contagious, chronic inflammatory, genetic, and metabolic diseases. An overview of the completed and terminated clinical trials aimed at preventing cardiovascular mortality by targeting various aspects of the complement system and inflammatory reaction is included. Most current treatments for cardiac inflammation and remodeling primarily target the renin-angiotensin-aldosterone system (RAAS), which prevents further remodeling by reducing myocardial workload. However, moving forward, there may be a place for emerging anti-complement therapeutics, which impair the inflammatory response that generates hypertrophy itself.
Keywords
Humans, Cardiomegaly, Complement System Proteins, Animals, Inflammation, Complement Activation, Renin-Angiotensin System, complement immune system, complement anaphylatoxins, cardiac inflammation, cardiac hypertrophy, cardiac remodeling, autoimmune diseases, cardiovascular events, infectious diseases, genetic defects in complement genes, complement in metabolic diseases, cardiovascular adversities, cardiovascular diseases, cardiac arrhythmias
Published Open-Access
yes
Recommended Citation
Hok, Kathryn D; Rich, Haydn E; Shadid, Anthony; et al., "Functional Roles of the Complement Immune System in Cardiac Inflammation and Hypertrophy" (2025). The Brown Foundation: Institute of Molecular Medicine. 132.
https://digitalcommons.library.tmc.edu/molecular_med/132