Cariporide counteracts atherosclerosis-related functions in monocytes from obese and normal individuals

This study aimed to show the effect of high glucose concentrations in combination with a pharmaceutical analog of the Na+/H+ antiport inhibitor, cariporide, on scavenger receptor CD36 expression, cell adhesion, and cell migration of human monocytes derived from obese and normal individuals.

Monocytes were isolated from six healthy obese individuals and six healthy age- and sex-matched controls by use of whole blood Percoll sedimentation and plastic surface monocyte binding. The density of CD36 scavenger receptors on the surface of monocytes was assessed by the use of a fluorescent fluorescein isothiocyanate (FITC)-linked monoclonal antibody. Transmigration of monocytes through laminin-1-coated filters was performed on 5-microm pore Transwell culture inserts. Monocyte attachment to laminin was estimated by a solid phase assay.

High glucose concentrations caused an increase in monocytes from normal and obese individuals in the expression of CD36 receptors and positively influenced monocyte migration and adhesion to laminin. Cariporide together with glucose counteracted these effects. The effects of migration and adhesion of monocytes to laminin were specific to glucose, because the effect was significantly higher when monocytes were incubated in the presence of 20 mM of glucose than in the presence of 20 mM of fructose. Monocytes from obese subjects showed greater response than in normal to all of the studied effects, with the highest response in laminin attachment.

The data of this study suggest that cariporide counteracts atherosclerosis-related functions through Na+/H+ antiport inhibition in monocytes from both normal and obese individuals.