Vitamin D intervention does not improve vascular regeneration in diet-induced obese male mice with peripheral ischemia

Kia M Peters; Richard Zhang; Chanho Park; Zengxuan Nong; Hao Yin; Rachel B Wilson; Brian G Sutherland; Cynthia G Sawyez; J Geoffrey Pickering; Nica M Borradaile

doi:10.1016/j.jnutbio.2019.04.010

Vitamin D intervention does not improve vascular regeneration in diet-induced obese male mice with peripheral ischemia

J Nutr Biochem. 2019 Aug:70:65-74. doi: 10.1016/j.jnutbio.2019.04.010. Epub 2019 May 10.

Authors

Affiliations

¹ Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada, N6A 5C1.
² Robarts Research Institute, Western, University, London, ON, Canada, N6A 5C1.
³ Robarts Research Institute, Western, University, London, ON, Canada, N6A 5C1; Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada, N6A 5C1; Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada, N6A 5C1; Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada, N6A 5C1; London Health Sciences, Centre, London, ON, Canada, N6A 5A5.
⁴ Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada, N6A 5C1. Electronic address: nica.borradaile@schulich.uwo.ca.

PMID: 31176988
DOI: 10.1016/j.jnutbio.2019.04.010

Abstract

Vitamin D appears to either promote or inhibit neovascularization in a disease context-dependent manner. The effects of vitamin D, alone or in combination with niacin, on endothelial cell (EC) angiogenic function and on revascularization in obese animals with peripheral ischemia are unknown. Here, we report that supplementation of high palmitate medium with vitamin D, niacin or both vitamins increased EC tube formation, which relies primarily on cell migration, and also maintained tube stability over time. Transcriptomic analyses revealed that both vitamins increased stress response and anti-inflammatory gene expression. However, vitamin D decreased cell cycle gene expression and inhibited proliferation, while niacin induced stable expression of miR-126-3p and -5p and maintained cell proliferation in high palmitate. To assess vascular regeneration, diet-induced obese mice received vitamin D, niacin or both vitamins following hind limb ischemic injury. Niacin, but not vitamin D or combined treatment, improved recovery of hind limb use. Histology of tibialis anterior sections revealed no improvements in revascularization, regeneration, inflammation or fibrosis with vitamin D or combined treatment. In summary, although both vitamin D and niacin increased angiogenic function of EC cultures in high fat, only niacin improved recovery of hind limb use following ischemic injury in obese mice. It is possible that inhibition of cell proliferation by vitamin D in high-fat conditions limits vascular regeneration and recovery from peripheral ischemia in obesity.

Keywords: 1,25-Dihydroxyvitamin D3; Angiogenesis; Endothelial cell; Lipotoxicity; PVD.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Movement
Cell Proliferation
Diet*
Endothelial Cells / cytology
Gene Expression Profiling
Hindlimb / blood supply
Inflammation
Ischemia / pathology*
Male
Metabolic Syndrome / pathology
Mice
Mice, Obese
Microcirculation
Neovascularization, Pathologic
Neovascularization, Physiologic / drug effects*
Niacin / pharmacology*
Palmitic Acid / pharmacology
Regeneration
Transcriptome
Veins / pathology*
Vitamin D / pharmacology*

Substances

Vitamin D
Niacin
Palmitic Acid