The association between zinc and endothelial adhesion molecules ICAMs and VCAM-1 and nuclear receptors PPAR-α and PPAR-γ: A systematic review on cell culture, animal and human studies

Background: Cardiovascular health is strongly influenced by diet. The levels of inflammatory factors like ICAM-1 and VCAM-1 are high in patients with atherosclerosis or predisposing factor for heart disease. Antioxidant and anti-inflammatory functions are attributed to zinc. We systematically reviewed cell culture, human or animal studies for determining the relationship between zinc status and ICAMs or VCAM-1 levels. Methods: PubMed, Google Scholar, Scopus, and Cochrane databases from database inception till 30th August 2020 were systematically searched to obtain any possible article for inclusion. Results: After screening and removing unrelated or duplicate articles by the title and abstract by two independent reviewers, 15 articles were included. Results indicating an inverse relationship between zinc status with ICAM-1 or VCAM-1 levels and the development of endothelial inflammation, plaque formation, or atherosclerosis. A direct relationship between zinc status and PPAR-alpha or gamma levels was also observed. Zinc oxide (ZnO), zinc nanoparticles, or ions can cause endothelial activation and increased levels of ICAM-1 and VCAM-1. Conclusion: Normal function of the endothelium is linked with zinc level. Zinc deficiency causes atherosclerosis, most probably via increased production of ICAM-1 and VCAM-1; and decreased expression of PPAR-alpha and PPAR-gamma receptors. Contrarily, endothelial activation and increased ICAM-1 and VCAM-1 levels can be caused by ZnO, zinc nanoparticles, or zinc ions.