Monocyte Chemoattractant Protein-1 (MCP-1) Is Associated with Impaired Membrane Fluidity of Red Blood Cells in Hypertensive Subjects: In Relation to Endothelial Dysfunction

[Speaker] Kazushi Tsuda:1
1:Cardiovascular and Metabolic Research Center, Kansai University of Health Sciences, Japan

Recent studies have shown that monocyte chemoattractant protein-1 (MCP-1), a chemokine, may actively participate in the pathophysiology of hypertension and other cardiovascular diseases. On the other hand, it is well recognized that abnormalities in physical properties of the cell membranes may strongly be linked to hypertension. The present study was undertaken to investigate possible relationships among MCP-1, endothelial function and membrane fluidity (a reciprocal value of membrane microviscosity) in hypertensive subjects using an electron spin resonance (ESR)-spectrometry. The order parameter (S) for the spin-label agents (5-nitroxide stearate) in red blood cells (RBCs) was significantly higher in hypertensive subjects (0.727+0.001, n=73) than in normotensive subjects (0.719+0.001, n=51, P<0.0001), indicating that membrane fluidity was decreased in hypertension. Plasma MCP-1 levels were significantly increased in hypertensive subjects compared with normotensive subjects (HT 207.1+5.6 pg/mL, n=73, NT 175.7+6.1 pg/mL, n=51, P<0.001). Plasma MCP-1 correlated with plasma asymmetric dimethylarginine (ADMA: an endogenous nitric oxide synthase inhibitor) levels (r=0.224, n=124, P<0.05), and inversely correlated with plasma nitric oxide-metabolites (r=-0.221, n=124, P<0.05). Furthermore, the order parameter (S) of RBCs significantly correlated with plasma MCP-1 (r=0.321, n=124, P<0.001) and ADMA levels, and inversely correlated with plasma nitric oxide-metabolites. The finding suggests that reduced membrane fluidity might be associated with elevated levels of MCP-1 and endothelial dysfunction. Multivariate regression analysis showed that, after adjusting for confounding factors, plasma MCP-1 might be an independent predictor of membrane fluidity of RBCs. The ESR study could support the hypothesis that MCP-1 might have a close correlation with impaired rheologic behavior of RBCs and microcirculatory disorders in hypertensive subjects via endothelial dysfunction, and further suggests that MCP-1 could be a biomarker for the management of hypertension.
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