Immunomodulation of IL-33 and IL-37 with Vitamin D in the Neointima of Coronary Artery: A Comparative Study between Balloon Angioplasty and Stent in Hyperlipidemic Microswine

Vikrant Rai,Devendra K Agrawal

doi:10.3390/ijms22168824

Vikrant Rai, Devendra K Agrawal

Open Access

https://doi.org/10.3390/ijms22168824

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Abstract

Inflammation is a major contributor to the development and progression of atherosclerosis. Interleukin (IL)-33 and IL-37, members of the IL-1 family, modulate inflammation, with IL-33 having a pro-inflammatory effect and IL-37 having anti-inflammatory properties. IL-37 is constitutively expressed at low levels but upregulated in inflammatory contexts. The aim of this study was to evaluate the effect of vitamin D on the expression of IL-33, IL-37, macrophages, and caspase-1 in the neointimal tissue of coronary artery in Yucatan microswine with vitamin D deficient, sufficient, and supplemented status. The intimal injury was induced by balloon angioplasty and stenting in the coronary artery, and tissues were harvested after 6 months. The expression of various proteins of interest was evaluated by immunostaining. Increased expression of IL-33 and IL-37 in the neointimal tissue of the vitamin D deficient, as compared to the sufficient and supplemented microswine, as revealed by histological evaluation and semi-quantitative analysis, suggested the immunomodulatory effect of vitamin D on the expression of IL-33 and IL-37. The minimal expression or absence of IL-33 and IL-37 expression in stented arteries is suggestive of an attenuated inflammatory response in stented arteries, compared to balloon angioplasty. The decreased IL-33 expression in the sufficient and supplemented microswine could be a potential mechanism for controlling the inflammatory process and neointima formation leading to attenuated luminal narrowing of the coronary artery. Overall, these results support supplementation of vitamin D to attenuate inflammation, neointima formation, and restenosis.

Highlights

Inflammation is known to play a vital role in the pathogenesis of atherosclerosis and coronary artery disease (CAD) [1,2,3]
This study aimed to investigate the effect of vitamin D status on the expression of IL-33 and IL-37, the macrophages population, and to correlate the expression of IL-33 and IL-37 with neointima formation and neointimal inflammation
Hematoxylin and eosin staining of the angioplasty and stented coronary arteries showed significantly reduced neointima formation in the vitamin D supplemented (VDSupp) group, compared to the vitamin D sufficient (VDSuff) and vitamin D deficient (VDDef) groups (Figure 1A,D,G,J) in microswine with angioplasty

Summary

Introduction

Inflammation is known to play a vital role in the pathogenesis of atherosclerosis and coronary artery disease (CAD) [1,2,3]. There is an interplay between these and other cytokines that determines the balance between pro-inflammatory and anti-inflammatory cellular responses. It is this balance that, in part, determines the progression of atherosclerosis and CAD. While cytokines, such as IL-10 and transforming growth factor (TGF)-β, have been known for some time and are widely accepted as being anti-inflammatory, another anti-inflammatory cytokine IL-37 has only recently been discovered [3,4,5,6,7]

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