Molecular basis of coronary artery disease–malignancy comorbidity: inflammation, immunometabolism, thrombosis, and cardio-oncology translation

Figures

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  Figure 1. Central mechanistic model of CAD–malignancy comorbidity. Shared drivers, including aging, cardiometabolic risk factors, and cancer therapy, promote CHIP-driven myeloid remodeling. This hub amplifies inflammasome activation, immunometabolic stress, thromboinflammation, and endothelial/checkpoint disruption, thereby contributing to CAD progression, tumor-promoting inflammation, immune evasion, cancer-associated thrombosis, and metastasis.

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  Figure 2. Mechanistic overview of CAD–malignancy comorbidity. Shared clinical risk factors (age, smoking, obesity, diabetes, dyslipidemia, chronic inflammation) converge with tumor type-specific modifiers (inflammation, hypercoagulability, platelet activation) and molecular pathways (clonal hematopoiesis, inflammasome activation, immune dysregulation, endothelial dysfunction, NETs, coagulation) to drive bidirectional cardiovascular and cancer pathology. Arrows indicate key interactions and amplification loops connecting vascular and oncologic disease processes.

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  Figure 3. Chronic inflammation as a shared driver of CAD–malignancy comorbidity. Systemic inflammatory mediators promote endothelial dysfunction, leukocyte recruitment, plaque progression, tumor growth, angiogenesis, immune evasion, and thromboinflammation. Clonal hematopoiesis-associated myeloid remodeling activates AIM2 and NLRP3 inflammasomes, amplifying IL-1β/IL-18 release and vascular inflammation. Anti-inflammatory strategies, including colchicine and inflammasome pathway modulation, may provide translational opportunities for selected high-risk patients.

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  Figure 4. Clonal hematopoiesis (CHIP) links cancer predisposition and coronary artery disease (CAD) through immune-cell remodeling, immunometabolic reprogramming, and inflammasome activation. CHIP-mutant myeloid cells activate AIM2 and NLRP3 inflammasomes, producing IL-1β and IL-18, which amplify vascular inflammation, plaque progression, and tumor-promoting inflammation. CHIP-informed anti-inflammatory strategies, such as colchicine and biomarker-guided monitoring, represent translational opportunities to mitigate cardiovascular risk while preserving oncologic control.

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  Figure 5. Immunometabolic remodeling links CAD and malignancy through shared macrophage and T-cell programs. In atherosclerotic plaques, metabolically reprogrammed macrophages promote lipid uptake, foam-cell formation, inflammasome activation, and plaque instability. In tumors, TAMs support angiogenesis, immune suppression, and metastasis. T-cell clonal expansion, tolerance failure, checkpoint imbalance, and CD40L–CD40 signaling further amplify vascular inflammation and tumor immune dysregulation.

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  Figure 6. Thromboinflammatory mechanisms linking CAD and malignancy. Platelet activation, endothelial dysfunction, coagulation cascade activation, and NET formation jointly promote plaque instability, arterial thrombosis, cancer-associated thrombosis, tumor cell survival, endothelial adhesion, and metastatic dissemination. Platelet–tumor cell crosstalk, VCAM-1-mediated endothelial activation, and NET-dependent fibrin scaffolds represent shared vascular mechanisms and potential therapeutic targets for antiplatelet, anticoagulant, endothelial-directed, and anti-inflammatory interventions.

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  Figure 7. Adaptive immune mechanisms linking atherosclerotic plaques and malignancy. Coronary plaques and tumors both contain antigen-experienced immune cells shaped by T-cell clonal expansion, tolerance failure, immune checkpoint regulation, and CD40L–CD40 signaling. Checkpoint pathways may restrain plaque inflammation while supporting tumor immune escape, whereas immune checkpoint blockade can enhance antitumor immunity but may also promote vascular immune activation and cardiovascular risk.