Paricalcitol Attenuates Metabolic Syndrome-Associated Heart Failure through Enhanced Mitochondrial Fusion. (11th June 2022)

• Record Type: Journal Article
• Authors: Nizami, Hina L.; Katare, Parmeshwar B.; Prabhakar, Pankaj; Adela, Ramu; Sarkar, Soumalya; Arava, Sudheer; Chakraborty, Praloy; Maulik, Subir K.; Banerjee, Sanjay K.
• Other Names: Ciobica Alin Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2022(2022)
• Publication Date: 2022-06-11
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2022/5554290
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : Objectives . Transition from cardiac hypertrophy to failure involves adverse metabolic reprogramming involving mitochondrial dysfunction. We have earlier shown that vitamin D deficiency induces heart failure, at least in part, through insulin resistance. However, whether activation of vitamin D receptor (VDR) can attenuate heart failure and underlying metabolic phenotype requires investigation. Thus, we aimed to assess the cardioprotective potential of paricalcitol, a vitamin D receptor-activator, against cardiac hypertrophy and failure in high-fat high-fructose-fed rats. Methods . Male Sprague Dawley rats were fed control (Con) or high-fat high-fructose (HFHFrD) diet for 20 weeks. After 12 weeks, rats from HFHFrD group were divided into the following: HFHFrD, HFHFrD+P (paricalcitol i.p. 0.08 μ g/kg/day) and HFHFrD+E (enalapril maleate i.p. 10 mg/kg/day). Intraperitoneal glucose tolerance test, blood pressure measurement, and 2D echocardiography were performed. Cardiac fibrosis was assessed by Masson's trichrome staining of paraffin-embedded heart sections. Mitochondrial DNA and proteins, and citrate synthase activity were measured in rat hearts. VDR was silenced in H9c2 cardiomyoblasts, and immunoblotting was performed. Results . Paricalcitol improved glucose tolerance, serum lipid profile, and blood pressure in high-fat high-fructose-fed rats. Paricalcitol reduced cardiac wall thickness and increased ejection fraction in high-fat high-fructose-fed rats but had no effect on perivascular fibrosis. PGC1- α was upregulated in the HFHFrD+P group compared to the HFHFrD group, but there was no significant difference in mitochondrial content. Citrate synthase activity was significantly higher in the HFHFrD+P group compared to the HFHFrD group. Rat hearts of the HFHFrD+P group had significantly higher expression of mitofusins. H9c2 cells with VDR knockdown showed significantly lower expression of Mfn2. Improvement in the HFHFrD+P group was comparable with that in the HFHFrD+E group. Conclusions . Paricalcitol reverses cardiac dysfunction in rats with metabolic syndrome by enhancing mitochondrial fusion. We demonstrate repurposing potential of the drug currently used in end-stage kidney disease.