Exogenously Added Oxyphytosterols Do Not Affect Macrophage‐Mediated Inflammatory Responses

Abstract

Although phytosterols, plant-derived sterol-like components, are well known for their cholesterol-lowering properties, their atherogenic potential is still under debate. Although they are known to share structural similarities with cholesterol, it is unclear whether their oxidized forms (oxyphytosterols) have the capacity to mediate proinflammatory responses in macrophages. In the present study, bone marrow-derived macrophages were treated with oxidized low-density lipoproteins, oxyphytosterols (7keto-sito/campesterol [7keto-sit/camp] or 7-beta-hydroxy-sito/campesterol [7βOH-sit/camp]), nonoxidized phytosterol (β-sitosterol), or carrier-control (cyclodextrin) in a dose- and time-dependent manner. Inflammatory cytokine release, activity, and the corresponding mRNA expression levels were analyzed. 7βOH-sit/camp, rather than 7keto-sit/camp, induced a modest proinflammatory response in wild-type cells derived from C57Bl/6 mice. The observed mild inflammatory effects are independent of the low-density lipoprotein receptor and Cluster of differentiation 36/Scavenger receptor-a. These data suggest that exogenously added oxyphytosterols do not affect macrophage-mediated inflammatory responses, at least in vitro.

Oxidative Stress, Atherogenic Dyslipidemia, and Cardiovascular Risk

“…Interestingly, although a pro-atherosclerotic role was confirmed for endogenous oxysterols, such as 7-ketocholesterol, similar conclusions cannot be drawn for oxyphytosterols. Namely, an in vitro study did not find evidence that oxyphytosterols influence macrophage-mediated inflammation [102]. Furthermore, analysis of data from the Framingham Offspring Study did not reveal any associations between plasma levels of oxyphytosterols and increased CVD risk [103].…”