Neuroimmune Regulation of Microvascular Inflammation: The Heart-Brain Axis, Mast Cells, and the Protective Role of Flavonoids-A Comprehensive Review
Abstract
Background/Objectives: Cardiovascular disease (CVD), particularly coronary artery disease (CAD), is increasingly linked to microvascular inflammation driven by interactions between immune, vascular, and neuroendocrine systems. Mast cells (MCs), strategically positioned near blood vessels, play pivotal roles in this process through the release of inflammatory and vasoactive mediators, contributing to increased vascular permeability, endothelial dysfunction, and tissue inflammation in conditions including ischemia-reperfusion (I/R) and CVD. This comprehensive review examines the cellular and molecular mechanisms underlying MC-mediated microvascular inflammation, with emphasis on neuroimmune regulation through the heart-brain axis, and evaluates the therapeutic potential of flavonoids. Methods: A review of in vitro, animal, and clinical studies was conducted to assess MC-mediated cardiovascular pathology and the pharmacological effects of natural flavonoids on MC activation and microvascular inflammation. Results: Psychological and physical stress activates hypothalamic corticotropin-releasing hormone (CRH) signaling, directly triggering coronary MC degranulation via CRHR-1 and CRHR-2 receptors, while co-released neuropeptides, including neurotensin and urocortin, amplify this neuroimmune cascade. Traumatic brain injury, autonomic dysregulation, and atrial fibrillation further perpetuate this bidirectional heart-brain axis, linking neurological stress to microvascular injury…
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