Department of Interventional Vascular Surgery, People's Hospital of Hunan Province, Changsha, P. R. China.
Eur Rev Med Pharmacol Sci. 2019 Feb;23(4):1816-1825. doi: 10.26355/eurrev_201902_17145.
Atherosclerosis, a kind of peripheral arterial disease with chronic inflammation, leads to the dysfunction of the vascular system and many other diseases. Hypoxia has been proven to participate in the progression of atherosclerosis, while curcumin can inhibit hypoxia-inducible factor 1α (HIF-1α). However, the underlying mechanisms are still elusive.
qRT-PCR was used to examine the expression of HIF-1α, IL-6 and TNFα of macrophages under hypoxic condition. Western blot was applied to examine the changes of HIF-1α, ERK and p-ERK after treatment with curcumin. Oli Red O staining and enzymatic assay were used to examine the lipid and total cholesterol in macrophages, respectively. ELISA was used to examine the release of IL-6 and TNFα by macrophages. FACS and MTT assays were applied to examine the apoptosis and proliferation of macrophages.
Here, we found curcumin inhibited the expression of HIF-1α at the protein level in macrophages under hypoxic condition and curcumin and HIF-1α inhibitors repressed the total cholesterol and lipid level in macrophage under hypoxic condition. Moreover, curcumin also decreased the expression of HIF-1α downstream genes, VEGF, HMOX1, ROS and PDGF. Then, the data show the HIF-1α-induced apoptosis and inflammation of macrophages were inhibited by curcumin. Curcumin also rescued the proliferation defect of macrophages caused by hypoxia. Furthermore, we found it inhibited the expression of HIF-1α via ERK signaling pathway.
We describe that curcumin inhibited the HIF-1α-induced apoptosis and inflammation of macrophages via ERK signaling pathways. These results suggest curcumin can be used for the treatment of atherosclerosis.
动脉粥样硬化是一种慢性炎症性外周动脉疾病，导致血管系统功能障碍和许多其他疾病。缺氧已被证明参与动脉粥样硬化的进展，而姜黄素可以抑制缺氧诱导因子 1α（HIF-1α）。然而，其潜在机制仍不清楚。
使用 qRT-PCR 检测缺氧条件下巨噬细胞中 HIF-1α、IL-6 和 TNFα 的表达。用 Western blot 检测姜黄素处理后 HIF-1α、ERK 和 p-ERK 的变化。油红 O 染色和酶法分别用于检测巨噬细胞中的脂质和总胆固醇。ELISA 用于检测巨噬细胞释放的 IL-6 和 TNFα。流式细胞术和 MTT 测定分别用于检测巨噬细胞的凋亡和增殖。
在这里，我们发现姜黄素在缺氧条件下抑制巨噬细胞中 HIF-1α的蛋白表达，并且姜黄素和 HIF-1α 抑制剂抑制缺氧条件下巨噬细胞中的总胆固醇和脂质水平。此外，姜黄素还降低了 HIF-1α下游基因 VEGF、HMOX1、ROS 和 PDGF 的表达。然后，数据表明 HIF-1α 诱导的巨噬细胞凋亡和炎症被姜黄素抑制。姜黄素还挽救了缺氧引起的巨噬细胞增殖缺陷。此外，我们发现它通过 ERK 信号通路抑制 HIF-1α 的表达。
我们描述了姜黄素通过 ERK 信号通路抑制 HIF-1α 诱导的巨噬细胞凋亡和炎症。这些结果表明姜黄素可用于治疗动脉粥样硬化。
