The cardiovascular-immune axis: crosstalk and therapy in atherosclerosis, myocarditis and vasculitis

Atherosclerosis (AS), myocarditis and vasculitis constitute a spectrum of prevalent cardiovascular diseases (CVDs) where immune dysregulation acts as a central pathogenic driver. Consequently, targeting the immune-cardiovascular axis represents a promising therapeutic frontier. This review systematically elucidates the shared immunological mechanisms underpinning these distinct yet interconnected conditions. The specific pathogenic landscapes are dissected, ranging from lipid-driven endothelial dysfunction and plaque instability in AS, to pathogen- or autoimmune-mediated myocardial injury in myocarditis, and necrotizing vessel wall inflammation in vasculitis. The fundamental roles of innate and adaptive immunity in driving cardiovascular pathology are delineated, highlighting the significant cross-talk and convergent immunological signatures among AS, myocarditis and vasculitis. Central to this convergence, CXCR4, PYCARD, TSC22D3 (GILZ), and HSPA1A are identified as critical hubs orchestrating leukocyte trafficking, inflammasome activation, immune tolerance, and proteostatic stress, respectively. Furthermore, precision strategies targeting these hubs are evaluated, utilizing agents such as Plerixafor, Lycorine, Dexamethasone, and Tanespimycin. Finally, emerging frontiers, including natural products and biomaterials, are assessed, providing a perspective on current clinical trials and future directions for resolving cardiovascular inflammation.