Chlamydia pneumoniae (Cpn) has been reported to be involved in the pathogenesis of early atherosclerosis by inducing macrophage-derived foam cell formation in the presence of low-density lipoprotein (LDL). However, the biochemical mechanisms underlying Cpn-induced foam cell formation are still not fully elucidated. The present study showed that in LDL-treated THP-1-derived macrophages, Cpn not only upregulated the expression of scavenger receptor A1 (SR-A1) and acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1), but it also downregulated the expression of ATP binding cassette transporters (ABCA1 and ABCG1) at both the mRNA and protein levels. These processes facilitated cholesterol accumulation and promoted macrophage-derived foam cell formation. Treatment with the peroxisome proliferator-activated receptor (PPAR)-γ agonist rosiglitazone or the PPARα agonist fenofibrate decreased the number of foam cells induced by Cpn, while the PPARγ antagonist GW9662, the PPARα antagonist MK886, or PPARα/γ siRNAs enhanced the effect of Cpn on foam cell formation and gene expression of SR-A1, ACAT1, and ABCA1/G1. Moreover, the PPARγ agonist rosiglitazone reversed the downregulation of CD36 by Cpn, while PPARγ siRNA and the PPARγ inhibitor GW9662 further suppressed CD36 expression. However, the PPARα agonist, inhibitor, and siRNA all showed no effect on CD36 expression. In conclusion, the PPARα and PPARγ pathways are both involved in Cpn-induced macrophage-derived foam cell formation by upregulating SR-A1 and ACAT1 and downregulating ABCA1/G1 expression.

据报道，肺炎衣原体( Cpn ) 通过在低密度脂蛋白 (LDL) 存在下诱导巨噬细胞衍生的泡沫细胞形成而参与早期动脉粥样硬化的发病机制。然而， Cpn诱导的泡沫细胞形成的生化机制仍未完全阐明。本研究表明，在 LDL 处理的 THP-1 衍生的巨噬细胞中，Cpn不仅上调清道夫受体 A1 (SR-A1) 和酰基辅酶 A：胆固醇酰基转移酶 1 (ACAT1) 的表达，而且在 mRNA 和蛋白质水平上下调 ATP 结合盒转运蛋白 (ABCA1 和 ABCG1) 的表达. 这些过程促进了胆固醇的积累并促进了巨噬细胞衍生的泡沫细胞的形成。过氧化物酶体增殖物激活受体 (PPAR)-γ 激动剂罗格列酮或 PPARα 激动剂非诺贝特治疗减少了Cpn诱导的泡沫细胞数量，而 PPARγ 拮抗剂 GW9662、PPARα 拮抗剂 MK886 或 PPARα/γ siRNA 增强了CPNSR-A1、ACAT1 和 ABCA1/G1 的泡沫细胞形成和基因表达。此外，PPARγ 激动剂罗格列酮逆转了Cpn对 CD36 的下调，而 PPARγ siRNA 和 PPARγ 抑制剂 GW9662 进一步抑制了 CD36 的表达。然而，PPARα 激动剂、抑制剂和 siRNA 均对 CD36 表达没有影响。总之，PPARα 和 PPARγ 通路均通过上调 SR-A1 和 ACAT1 并下调 ABCA1/G1 表达参与Cpn诱导的巨噬细胞衍生的泡沫细胞形成。