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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\u2013NF\u2010\u03baB signaling, NLRP3 inflammasomes, cGAS\u2013STING\u2010dependent cytosolic DNA sensing, alternative mitochondrial nucleic acid\u2010sensing platforms, and redox\u2010immunometabolic gating. We highlight mitochondrial quality control and mitochondria\u2010derived DAMPs, including mtDNA, mtROS, ATP, cardiolipin, and oxidized lipids, as an upstream interface linking metabolic stress to sterile immune activation. We further organize disease\u2010specific inflammatory patterns through a stage\u2010cell\u2010threshold perspective across ischemic injury, vascular and metabolic disease, and cardiomyopathic remodeling. Finally, we discuss network\u2010guided 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.<\/jats:p>","DOI":"10.1002\/mco2.70878","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T06:54:27Z","timestamp":1784530467000},"source":"Crossref","is-referenced-by-count":3,"title":["The Role of Inflammation and Immunity in Cardiovascular Disease: Molecular Mechanisms and Therapeutic Targets"],"prefix":"10.1002","volume":"7","author":[{"given":"Jiaxiang","family":"Rong","sequence":"first","affiliation":[{"name":"Shaanxi Province Key Laboratory of New Drugs and Chinese Medicine Foundation Research, School of Pharmacy Shaanxi University of Chinese Medicine  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Shaanxi Province Key Laboratory of New Drugs and Chinese Medicine Foundation 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