Discipline of Biosciences and Biomedical Engineering (BSBE), Indian Institute of Technology Indore (IITI), Simrol-453552, Indore, MP, India.
Discipline of Chemistry, Indian Institute of Technology Indore (IITI), Simrol-453552, Indore, MP, India.
Int Immunopharmacol. 2020 Jun;83:106382. doi: 10.1016/j.intimp.2020.106382. Epub 2020 Mar 16.
Vascular inflammation plays a decisive role in the formation of foam cells and in the pathophysiology of atherosclerosis. However, the underlying mechanisms of these processes are not clearly understood. Macrophages engulf oxidized low-density lipoproteins (OxLDLs) via a scavenger receptor (SR), an event that mediates the elaboration of proinflammatory cytokines to initiate necrotic core formation in atherogenic plaques. In this study, we demonstrate that Nitric oxide synthase 1 (NOS1)-derived nitric oxide (NO) promotes OxLDL uptake and enhances the release of proinflammatory cytokines by macrophages. Conversely, we show that NOS1 inhibition by N(G)-nitro-L-arginine methyl ester (L-NAME) suppresses OxLDL uptake and proinflammatory cytokine expression. Current studies indicate that NOS1 plays a crucial role in vascular inflammation and in the progression of atherosclerosis. Therefore, interference with NOS1 enzymatic activity should serve as an effective strategy to reduce foam cell formation and limit the extent of atherosclerotic plaque expansion.
血管炎症在泡沫细胞的形成和动脉粥样硬化的病理生理学中起着决定性的作用。然而，这些过程的潜在机制尚不清楚。巨噬细胞通过清道夫受体 (SR) 吞噬氧化型低密度脂蛋白 (OxLDL)，这一事件介导了促炎细胞因子的产生，从而启动动脉粥样硬化斑块中坏死核心的形成。在这项研究中，我们证明一氧化氮合酶 1 (NOS1) 衍生的一氧化氮 (NO) 促进 OxLDL 的摄取，并增强巨噬细胞释放促炎细胞因子。相反，我们表明，N(G)-硝基-L-精氨酸甲酯 (L-NAME) 通过 NOS1 抑制抑制 OxLDL 的摄取和促炎细胞因子的表达。目前的研究表明，NOS1 在血管炎症和动脉粥样硬化的进展中起着至关重要的作用。因此，干扰 NOS1 的酶活性应该是减少泡沫细胞形成和限制动脉粥样硬化斑块扩张的有效策略。
