Aortic dissection: the role of macrophages in disease pathogenesis and their potential as a treatment target

主动脉夹层:巨噬细胞在疾病发病机制中的作用及其作为治疗靶点的潜力

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Abstract

Aortic dissection (AD) is a life-threatening cardiovascular emergency characterized by an intimal tear that allows blood to enter the medial layer of the aortic wall, creating a false lumen. This process separates the layers within the media and may extend longitudinally along the aorta, sometimes progressing to aortic rupture if not promptly managed. Patients often present with sudden and severe chest, back, or abdominal pain, and clinical manifestations vary depending on the location and extent of the dissection. The underlying mechanisms of AD remain incompletely understood, but emerging evidence suggests that immune cell activation, particularly macrophage-mediated inflammation, plays a critical role in disease initiation and progression. Existing evidence indicates that macrophages polarize toward the classic (M1) phenotype, releasing proinflammatory cytokines and matrix-degrading enzymes that exacerbate vascular injury. Conversely, type 2 macrophages (M2) are activated in response to M1 macrophage exhaustion and other regulatory signals, exerting anti-inflammatory and tissue-repair functions. Therefore, M2 macrophages may represent a promising molecular target for therapeutic intervention. Macrophage infiltration also contributes to vascular smooth muscle cell phenotypic switching, endothelial dysfunction, and extracellular matrix degradation. In this review, we discuss the role of macrophages in the pathogenesis of AD, summarize their involvement in key pathological processes, and highlight molecular signaling pathways linking macrophage activation to AD development. Furthermore, we explore the therapeutic potential of modulating macrophage polarization as a strategy for AD treatment.

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