Diabetes mellitus leads to an impaired reverse migration capacity of CD14++ monocytes causing a subluminal accumulation

Atherosclerosis as a chronic inflammation is driven by multiple cardiovascular risk factors, such as diabetes mellitus (DM). Monocytes represent the biggest cell population in the atherosclerotic aorta. DM induces oxidative stress, which causes a monocytic dysfunction. Albeit it is known that DM leads to an monocytic accumulation within the inflammatory tissue and induces plaque formation, it remains unclear which mechanisms drive the accumulation in diabetic environment. To investigate the DM induced changes in monocytic diapedesis in vitro a flow assay model was established. CD14++ monocytes of patients, who either suffered from type 2 diabetes mellitus (T2DM) or not (nonDM), were isolated. Besides CD14++ monocytes, isolated from healthy donors, were conditioned in normo- or hyperglycemic evironment. An endothelial monolayer was activated and then perfused with the monocytes. The experiments were performed under physiological flow conditions that can be found in postcapillary venules. The data was analysed by single cell tracking using the Fiji J software. In this project, we could prove a significant reduced transendothelial migration capacity of T2DM- and hyperglycemia-conditioned monocytes. An extended stay of monocytes in the albumen after transendothelial migration was revealed. Moreover, the capacity of the monocytes to undergo reverse migration was reduced and lead to an accumulation after transendothelial migration. This suggests, that the enhanced monocytic accumulation in DM could be associated with a dysfunctional reverse transendothelial migration and is not due to a quantitatively enhanced diapedesis. We indicate that restoring the impaired reverse migration could reduce the accumulation of monocytes and atherogenesis within diabetic environment.

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Publication History

Article published online:
19 August 2021