Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 24, Issue 16, Pages 9189-9203Publisher
WILEY
DOI: 10.1111/jcmm.15556
Keywords
atorvastatin; heart; insulin resistance; obesity; oestrogen deprivation; PCSK9 inhibitor
Categories
Funding
- National Science and Technology Development Agency Thailand
- Thailand Research Fund [RSA6180056, RSA6180071, MRG6280014]
- Chiang Mai University Center of Excellence Award
- National Research Council of Thailand
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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 mu g/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.
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