Despite the availability of many therapeutic options, the prevalence of hypercholesterolemia remains high. There exists a significant unmet medical need for novel drugs and/or treatment combinations to effectively combat hypercholesterolemia while minimizing adverse reactions. The modulation of cholesterol 7α-hydroxylase (CYP7A1) expression via perturbation of the farnesoid X receptor (FXR) – dependent pathways, primarily FXR/small heterodimer partner (SHP) and FXR/ fibroblast growth factor (FGF)-19/ fibroblast growth factor receptor (FGFR)-4 pathways, presents as a potential option to lower cholesterol levels. This paper provides a comprehensive review of the important role that CYP7A1 plays in cholesterol homeostasis and how its expression can be exploited to assert differential control of bile acid synthesis and cholesterol metabolism. Additionally, the paper also summarizes the current therapeutic options for hypercholesterolemia, and positions modulators of CYP7A1 expression, namely FGFR4 inhibitors and FXR antagonists, as emerging and distinct pharmacological agents to complement and diversify the treatment regime. Their mechanistic and clinical considerations are also extensively described to interrogate the benefits and risks associated with using FXR-mediating agents, either singularly or in combination with recognised agents such as statins to target hypercholesterolemia.

尽管有许多治疗选择，高胆固醇血症的患病率仍然很高。对于有效对抗高胆固醇血症同时最小化不良反应的新型药物和/或治疗组合存在显着的未满足的医疗需求。通过干扰法尼醇 X 受体 (FXR) 依赖性途径，主要是 FXR/小异二聚体伴侣 (SHP) 和 FXR/ ​​成纤维细胞生长因子 (FGF)-19/ 成纤维细胞生长因子受体，调节胆固醇 7α-羟化酶 ( CYP7A1 ) 表达(FGFR)-4 途径是降低胆固醇水平的潜在选择。本文全面综述了CYP7A1在胆固醇稳态中发挥的重要作用，以及如何利用其表达来对胆汁酸合成和胆固醇代谢进行差异控制。此外，本文还总结了当前高胆固醇血症的治疗选择，并将CYP7A1表达调节剂（即 FGFR4 抑制剂和 FXR 拮抗剂）定位为新兴且独特的药物，以补充和多样化治疗方案。他们的机制和临床考虑也被广泛描述，以询问与使用 FXR 介导药物相关的益处和风险，无论是单独使用还是与公认的药物（如他汀类药物）联合使用来治疗高胆固醇血症。