Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku 160-8582, Tokyo, Japan.
Department of Cardiology, Tokyo Dental College Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa 272-8513, Chiba, Japan.
Int J Mol Sci. 2023 Apr 1;24(7):6619. doi: 10.3390/ijms24076619.
Mast cells are responsible for IgE-dependent allergic responses, but they also produce various bioactive mediators and contribute to the pathogenesis of various cardiovascular diseases, including pulmonary hypertension (PH). The importance of lipid mediators in the pathogenesis of PH has become evident in recent years, as exemplified by prostaglandin I2, the most central therapeutic target in pulmonary arterial hypertension. New bioactive lipids other than eicosanoids have also been identified that are associated with the pathogenesis of PH. However, it remains largely unknown how mast cell-derived lipid mediators are involved in pulmonary vascular remodeling. Recently, it has been demonstrated that mast cells produce epoxidized n-3 fatty acid (n-3 epoxides) in a degranulation-independent manner, and that n-3 epoxides produced by mast cells regulate the abnormal activation of pulmonary fibroblasts and suppress the progression of pulmonary vascular remodeling. This review summarizes the role of mast cells and bioactive lipids in the pathogenesis of PH. In addition, we introduce the pathophysiological role and therapeutic potential of n-3 epoxides, a mast cell-derived novel lipid mediator, in the pulmonary vascular remodeling in PH. Further knowledge of mast cells and lipid mediators is expected to lead to the development of innovative therapies targeting pulmonary vascular remodeling.
肥大细胞负责 IgE 依赖性过敏反应，但它们也产生各种生物活性介质，并有助于各种心血管疾病的发病机制，包括肺动脉高压 (PH)。近年来，脂类介质在 PH 发病机制中的重要性已经显而易见，例如前列腺素 I2 是肺动脉高压的最核心治疗靶点。除了类二十烷酸之外，还发现了与 PH 发病机制相关的其他新的生物活性脂质。然而，肥大细胞衍生的脂质介质如何参与肺血管重塑在很大程度上仍然未知。最近已经证明，肥大细胞以脱颗粒非依赖性的方式产生环氧-n-3 脂肪酸 (n-3 环氧化物)，并且由肥大细胞产生的 n-3 环氧化物调节肺成纤维细胞的异常激活并抑制肺血管重塑的进展。这篇综述总结了肥大细胞和生物活性脂质在 PH 发病机制中的作用。此外，我们介绍了 n-3 环氧化物作为一种肥大细胞衍生的新型脂质介质在 PH 中肺血管重塑的病理生理作用和治疗潜力。进一步了解肥大细胞和脂质介质有望导致针对肺血管重塑的创新治疗方法的发展。
