Macrophage folate receptor-β (FR-β) expression in auto-immune inflammatory rheumatic diseases: A forthcoming marker for cardiovascular risk?

In patients with systemic auto-immune inflammatory rheumatic diseases (AIIRD) like rheumatoid arthritis the prevalence of cardiovascular disease (CVD) is increased. In the pathogenesis of AIIRD and atherosclerosis many similarities can be found in the process underlying CVD. Accumulation of inflammatory cells, in particular macrophages at the site of inflammation producing inflammatory mediators serve as a prominent feature in both systemic inflammation and atherosclerosis.Two different subtypes of macrophages have been described in recent literature namely classically activated macrophages (M1) and alternatively activated macrophages (M2). Alternatively activated macrophages are characterized by low CD14 and high CD163 expression. Macrophages expressing CD14 (M1) have been identified within atherosclerotic plaques, whereas CD14 low macrophages are abundant in vessels without atherosclerosis. Depending on the environment and responses to different stimuli, macrophages in plaques can express diverse pro and anti-atherogenic functions. The balance of these different activation profiles influences atheroma evolution and outcome.Nowadays, influx of macrophages is recognized as a very important feature of the pathogenesis of plaque formation. Activated macrophages accumulate at the sites of inflammation and can therefore be exploited to better visualize inflammatory responses in atherosclerosis. Furthermore, activated (but not resting) macrophages possess a functionally active receptor for folate (FR-β), but it is not completely clear which subtype of this activated macrophages expresses this receptor and whether the expression of FR-β is restricted to only one of the macrophage subsets. Although future research needs to be done to investigate FR-β expression and function within inflamed tissues, the expression of functional FR-β on tissue macrophages likely occurs during activation. Therefore, expression of FR-β on activated macrophages holds a promising potential for early diagnosis and better analysis of optimal treatment regiments of vascular diseases in association with systemic diseases.

► Macrophages play an important role in the pathogenesis of both AIIRD and atherosclerosis and might link these diseases.
► Macrophages can be distinguished in M1 and M2 subtypes.
► The balance between M1 and M2 macrophages will influence plaque vulnerability.
► FR-β, a marker for M2 macrophages, could be a tool for early detection of atherosclerosis.