The Role of Inflammation and Immunity in Cardiovascular Disease: Molecular Mechanisms and Therapeutic Targets
TL;DR
Evidence on immune landscapes and core inflammatory networks in cardiovascular diseases are synthesized, focusing on TLR–NF‐κB signaling, NLRP3 inflammasomes, cGAS–STING‐dependent cytosolic DNA sensing, alternative mitochondrial nucleic acid‐sensing platforms, and redox‐immunometabolic gating, to provide a conceptual basis for moving cardiovascular inflammatory therapy from broad suppression toward more precise network regulation.
Abstract
Cardiovascular inflammation is increasingly recognized not merely as a secondary response to hemodynamic or metabolic injury, but as a determinant of disease initiation, progression, and remodeling. In the injured heart and vasculature, danger sensing, inflammatory priming, inflammasome activation, nucleic acid recognition, immunometabolic rewiring, immunothrombosis, adaptive immune remodeling, and defective resolution form interdependent circuits rather than isolated pathways. A key challenge is to understand how these circuits shift from adaptive clearance and repair to persistent immune activation, fibrosis, and functional decline. Here, we synthesize evidence on immune landscapes and core inflammatory networks in cardiovascular diseases, focusing on TLR–NF‐κB signaling, NLRP3 inflammasomes, cGAS–STING‐dependent cytosolic DNA sensing, alternative mitochondrial nucleic acid‐sensing platforms, and redox‐immunometabolic gating. We highlight mitochondrial quality control and mitochondria‐derived DAMPs, including mtDNA, mtROS, ATP, cardiolipin, and oxidized lipids, as an upstream interface linking metabolic stress to sterile immune activation. We further organize disease‐specific inflammatory patterns through a stage‐cell‐threshold perspective across ischemic injury, vascular and metabolic disease, and cardiomyopathic remodeling. Finally, we discuss network‐guided therapeutic strategies, translational limitations, biomarkers, endpoints, and safety considerations. This integrated perspective provides a conceptual basis for moving cardiovascular inflammatory therapy from broad suppression toward more precise network regulation.