Post‐menopausal women have a higher risk of developing cardiometabolic dysfunction. Atorvastatin attenuates dyslipidaemia and cardiac dysfunction but it can have undesirable effects including increased risk of diabetes and myalgia. Currently, the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor efficiently reduces low‐density lipoprotein cholesterol (LDL‐C) levels more effectively than atorvastatin. We have been suggested that PCSK9 inhibitor attenuated cardiometabolic impairment more effectively than atorvastatin in ovariectomized prediabetic rats. Female Wistar rats (n = 48) were fed a normal diet (ND) or high‐fat diet (HFD) for 12 weeks. Then, HFD rats were assigned to a sham‐operated (Sham) or ovariectomized (OVX) group. Six weeks after surgery, the OVX group was subdivided into 4 treatment groups: vehicle (HFOV), atorvastatin (HFOA) (40 mg/kg/day; s.c.), PCSK9 inhibitor (HFOP) (4 mg/kg/day; s.c.) and oestrogen (HFOE₂) (50 µg/kg/day; s.c.) for an additional 3 weeks. Metabolic parameters, cardiac and mitochondrial function, and [Ca²⁺]_i transients were evaluated. All HFD rats became obese‐insulin resistant. HFS rats had significantly impaired left ventricular (LV) function, cardiac mitochondrial function and [Ca²⁺]_i transient dysregulation. Oestrogen deprivation (HFOV) aggravated all of these impairments. Our findings indicated that the atorvastatin, PCSK9 inhibitor and oestrogen shared similar efficacy in the attenuation in cardiometabolic impairment in ovariectomized prediabetic rats.

中文翻译：

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PCSK9 抑制剂和阿托伐他汀通过改善线粒体功能和 Ca2+ 调节减轻去卵巢糖尿病前期大鼠的心脏损伤。

绝经后妇女发生心脏代谢功能障碍的风险更高。阿托伐他汀可减轻血脂异常和心脏功能障碍，但它会产生不良影响，包括增加患糖尿病和肌痛的风险。目前，前蛋白转化酶枯草杆菌蛋白酶 / kexin 9 型 (PCSK9) 抑制剂比阿托伐他汀更有效地降低低密度脂蛋白胆固醇 (LDL-C) 水平。我们已经提出 PCSK9 抑制剂比阿托伐他汀更有效地减轻卵巢切除的糖尿病前期大鼠的心脏代谢损伤。雌性 Wistar 大鼠 (n = 48) 被喂食正常饮食 (ND) 或高脂肪饮食 (HFD) 12 周。然后，HFD 大鼠被分配到假手术 (Sham) 或卵巢切除 (OVX) 组。手术后六周，OVX 组被细分为 4 个治疗组：赋形剂 (HFOV)、₂ ) (50 µg/kg/天；sc) 额外 3 周。评估了代谢参数、心脏和线粒体功能以及 [Ca ²⁺ ] _i瞬变。所有 HFD 大鼠都变得肥胖胰岛素抵抗。HFS 大鼠的左心室 (LV) 功能、心脏线粒体功能和 [Ca ²⁺ ] _i瞬时失调明显受损。雌激素剥夺 (HFOV) 加重了所有这些损害。我们的研究结果表明，阿托伐他汀、PCSK9 抑制剂和雌激素在减轻卵巢切除的糖尿病前期大鼠心脏代谢损伤方面具有相似的功效。