Neuro-immune interactions in coronary microvascular disease : Mechanisms and Therapeutic Prospect

Zhao Ge^1,2Guoyu Wu^1,2Jingguo Ma^1,2Silin Ren^1,2Tongzuo Liu^1,2Xudong Wu^1,2Xianliang Wang^2*

• ¹Tianjin University of Traditional Chinese Medicine, Tianjin, China
• ²First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China

Coronary microvascular disease (CMVD) represents a widespread but frequently underdiagnosed cardiovascular condition marked by endothelial dysfunction and inflammatory microvascular remodeling. Mounting evidence underscores the pivotal involvement of neuro-immune interactions in CMVD pathogenesis, encompassing complex bidirectional communication among the autonomic nervous system, immune cells, and vascular endothelium. This review first examines the evolving paradigm of neuro-immune cardiovascular circuits and elucidates critical signaling pathways—including NF-κB, MAPK, mTOR, STAT3, and cAMP—that govern these interactions. Subsequently, to provide a clinical context for these underlying mechanisms, we present an in-depth analysis of recent clinical trials. We evaluate the evidence from large-scale cardiovascular outcome trials of anti-inflammatory agents like colchicine, alongside mechanism-based trials of vasodilators, novel cell-based therapies, and other targeted agents specifically in the CMVD population. This clinical evidence highlights the therapeutic promise of immunomodulation while underscoring the limitations of empirical, non-stratified treatment approaches. Finally, we posit that future progress depends on precision medicine frameworks that integrate neuro-immune profiling with mechanism-based patient stratification. By synthesizing contemporary mechanistic understanding and robust clinical evidence, this review advances novel diagnostic and therapeutic perspectives through a neuro-immunological lens.