Cariporide Counteracts Atherosclerosis‐related Functions in Monocytes from Obese and Normal Individuals

Abstract

Research Methods and Procedures:Monocytes were isolated from six healthy obese individuals and six healthy ageand 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-m pore Transwell culture inserts. Monocyte attachment to laminin was estimated by a solid phase assay. Results: 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. Discussion: The data of this study suggest that cariporide counteracts atherosclerosis-related functions through Na ϩ /Hϩ antiport inhibition in monocytes from both normal and obese individuals.

Cariporide inhibits high glucose-mediated adhesion of monocyte–endothelial cell and expression of intercellular adhesion molecule-1

“…Thus, inhibition of adhesion of leukocytes is a pharmacological approach to attenuate hyperglycemia-induced vascular inflammatory disorders. Kaloyianni et al (2005) have reported that cariporide, a NHE-1 inhibitor, may inhibit the high glucose-caused expression of CD36 receptors, migration and adhesion to laminin in monocytes from both normal and obese individuals. We also found that cariporide significantly attenuated the adhesion of monocytes to endothelial cells and the expression of ICAM-1 in endothelial cells cultured in high glucose medium.…”

Inhibitory effects of cariporide on LPC-induced expression of ICAM-1 and adhesion of monocytes to smooth muscle cells in vitro

“…Jung et al [22] reported that acute and chronic treatment with cariporide significantly reduced the infarct size of myocardium induced by coronary artery occlusion in rabbits fed an atherogenic or normal diet, and chronic cariporide treatment also prevented dysfunction of endothelium-dependent relaxation induced by an atherogenic diet [23] . Kaloyianni et al [24] demonstrated that high glucose solution caused an activation of NHE-1 in human monocytes and in turn, stimulated the increase of the expression of CD36 receptors on the surface of monocytes from normal and obese individuals; it positively influenced monocyte migration and adhesion to laminin, the sodium/hydrogen ion exchange inhibitor. Cariporide or ethylisopropyl amiloride counteracted these effects caused by high glucose solution [23,24] .…”

“…Kaloyianni et al [24] demonstrated that high glucose solution caused an activation of NHE-1 in human monocytes and in turn, stimulated the increase of the expression of CD36 receptors on the surface of monocytes from normal and obese individuals; it positively influenced monocyte migration and adhesion to laminin, the sodium/hydrogen ion exchange inhibitor. Cariporide or ethylisopropyl amiloride counteracted these effects caused by high glucose solution [23,24] . Based on these results, we presume that the activation of NHE-1 plays a crucial role in those effects induced by LPC.…”

The role of hyperglycemia in FAT/CD36 expression and function

“…Northern hybridization RNA was isolated as described by Chomczynski and Sacchi [12] using Total RNA Isolation Reagent (GIBCO BRL). Total RNA (20-25 lg) was electrophoresed on 1.2% agarose gel containing formaldehyde, transferred to Nylon membranes by Rapid Downward Transfer Systems (Schleicher & Schuell).…”

“…Many studies have shown that CD36 mRNA is differentially altered in skeletal and left ventricular cardiac muscle in streptozotocin (STZ)-induced type 1 diabetic rats [10,11]. In vitro studies, it has been shown that glucose can up regulate FAT/ CD36 mRNA and protein levels [12,13]. However, the specific in vivo relationship between plasma glucose levels and tissue FAT/CD36 expression has not been clearly established.…”