loading page

Paricalcitol reverses metabolic syndrome-associated heart failure through enhanced mitochondrial fusion
  • +6
  • Hina Lateef Nizami,
  • Parmeshwar Katare,
  • Pankaj Prabhakar,
  • Ramu Adela,
  • Soumalya Sarkar,
  • Sudheer Arava,
  • Praloy Chakraborty,
  • Subir Maulik,
  • Sanjay Banerjee
Hina Lateef Nizami
Translational Health Science and Technology Institute
Author Profile
Parmeshwar Katare
Translational Health Science and Technology Institute
Author Profile
Pankaj Prabhakar
All India Institute of Medical Sciences
Author Profile
Ramu Adela
All India Institute of Medical Sciences
Author Profile
Soumalya Sarkar
Translational Health Science and Technology Institute
Author Profile
Sudheer Arava
All India Institute of Medical Sciences
Author Profile
Praloy Chakraborty
Vardhman Mahavir Medical College and Safdarjung Hospital
Author Profile
Subir Maulik
All India Institute of Medical Sciences
Author Profile
Sanjay Banerjee
Translational Health Science and Technology Institute
Author Profile

Abstract

Background & Purpose: We have earlier shown that vitamin D deficiency induces heart failure, in part, through insulin resistance. Whether activation of vitamin D receptor can attenuate heart failure, associated with metabolic syndrome, requires investigation. We aimed to assess cardioprotective potential of paricalcitol, a vitamin D receptor-activator, in high fat high fructose-fed rats. Experimental approach: Male Sprague Dawley rats were fed with control (Con) or high fat high fructose (HFHFrD) diet for 20 weeks. After 12 weeks, rats from HFHFrD group were divided into: HFHFrD, HFHFrD+P (paricalcitol i.p. 0.08 ug/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 in Masson trichrome-stained 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. Key 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, with no effect on perivascular fibrosis. PGC1-α was uprgulated in HFHFrD+P group compared to HFHFrD group, without significant difference in mitochondrial content. Citrate synthase activity was significantly higher in HFHFrD+P group compared to HFHFrD group. Rat hearts of HFHFrD+P group had significantly higher expression of mitofusins. H9c2 cells with VDR knockdown showed significantly lower expression of Mfn2. Conclusion & Implications: Paricalcitol is cardioprotective in rats with metabolic syndrome, through improved mitochondrial dynamics, indicating repurposing potential.