Ion transport, membrane fluidity and haemoglobin conformation in erythrocyte from patients with cardiovascular diseases: Role of augmented plasma cholesterol

Abstract

Tissue hypoxia, which plays a key role in the development of renal and vascular complications of cardiovascular diseases (CVD), might be considered a consequence of vascular remodeling and/or attenuated oxygen (O(2)) delivery by erythrocytes. Using Raman spectroscopy (RS), we observed that erythrocytes from patients with CVD exhibit changes in the conformation of haemoglobin (Hb) haemoporphyrin (HP), reflecting its lower O(2) transport capacity. Hypertriglyceridemia and hypercholesterolemia are well-known hallmarks of CVD. This study examined the role of plasma lipids in the regulation of erythrocyte membrane viscosity, oxy-Hb content as well as Na(+)/H(+) exchange and Ca(2+)-ATPase, whose activities are altered in patients with CVD. HP conformation was assessed by RS of blood samples. Membrane fluidity was estimated at depths of 0.6-0.8 and 2.2nm by electron-paramagnetic resonance spectroscopy of erythrocytes loaded with spin-labeled 5-doxylstearic acid and 16-doxylstearic acid, respectively. Ion-selective electrodes were employed for the study of H(+) and Ca(2+) fluxes. Both oxy-Hb content and erythrocyte membrane fluidity were decreased in essential hypertension and coronary artery disease patients and negatively correlated with plasma cholesterol but not triglyceride content. This observation allows us to assume that decreased oxy-Hb content in patients with CVD is caused by high plasma cholesterol via attenuation of erythrocyte membrane fluidity and its permeability to O(2). Plasma cholesterol level correlated positively and negatively with erythrocyte Na(+)/H(+) exchange and Ca(2+)-ATPase, respectively. However, in contrast to membrane fluidity, the impact of these ion transporters in oxy-Hb regulation under baseline conditions seems to be negligible. We propose that decreased oxy-Hb content contributes to the reduced O(2) tissue supply seen in patients with CVD.