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Cardiovascular stress signals (e.g., hemodynamic shear, oxidized lipids, and ischemia) act on endothelial and immune cells to activate and amplify inflammation through NF-κB, the NLRP3 inflammasome, and JAK/STAT signaling, inducing proinflammatory cytokines/chemokines (IL-6, IL-1β, TNF-α, and CCL2) and self-amplifying circuits; clinically, inflammatory burden is reflected by biomarkers such as hs-CRP, IL-6, and Lp-PLA2. In parallel, immune cells undergo metabolic remodeling (e.g., glucose flux through glycolysis to pyruvate/lactate vs. OXPHOS and fatty-acid oxidation), which tunes immune function and cell-fate decisions and contributes to atherosclerotic plaque instability. Cellular stress triggers regulated death modalities (apoptosis, autophagy, and ferroptosis), releasing DAMPs (e.g., ATP, HMGB1, and mtDNA) that reshape the cytokine/DAMP milieu and further modulate immunity between effector/proinflammatory programs (e.g., M1 macrophages, ROS, and Th1/Th17) and resolution/repair programs (e.g., M2 macrophages, Tregs, and IL-10). Together, these interconnected processes culminate in myocardial remodeling and injury, highlighting the IICM systems perspective as a foundation for CVD precision medicine.
Credit
Dezhi Guo and Wangzheqi Zhang
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