Abstract 161: Susceptibility to Activation of Human Monocytes in Asymptomatic Atherosclerosis
Monocytes were isolated from blood of three groups of patients, namely those with normal carotid intima-media thickness (CIMT), patients with increased CIMT and patients with plaques in carotid arteries. To assess susceptibility of isolated monocytes to M1 and M2 activation, cells were placed in primary culture with the appropriate stimulator for activation. The degree of M1 or M2 activations was determined by the culture medium level of TNFα and CCL18, respectively. When comparing the average values of TNFα and CCL18 in patients of three groups we were faced with dramatic individual differences. These individual differences have been found both within each group of patients and in the pool (groups 1+2+3). [[Unable to Display Character: М]]onocytes in early atherosclerotic lesions may migrate back into the circulation, possibly serving as a lipid clearance system. Circulating cells laden with lipid have been found in blood. We attempted to find the relationship between cholesterol in monocytes and their susceptibility to activation. There was an obvious trend towards a reverse correlation between intracellular cholesterol level and susceptibility to activation. To reveal the reason of relationship between intracellular cholesterol level and monocyte susceptibility to activation, the experiments on cells cultured with atherogenic modified LDL were carried out. LDL isolated from blood of patients with documented atherosclerosis induces cholesterol accumulation in cultured cells, while LDL from healthy subjects does not affect intracellular cholesterol level. Although modified LDL induced cholesterol accumulation in cultured monocyte-derived cells neither cytokine secretion nor cytokine genes expression were affected. Therefore no LDL but other sources of lipids accumulated in circulating monocytes determine their susceptibility to activation. We consider that difference in monocyte activation is very important because it may determine functional capacity of innate immunity in different patients. Cellular test cell used in this study may serve as a basis for diagnostic method for determining the individual response of innate immunity. This model may be used for the search of new immune correctors. Supported by Russian Scientific Foundation (Grant # 14-15-00112).
Author Disclosures: A.N. Orekhov: None. N.E. Nikiforov: None. N.V. Elizova: None.
- © 2015 by American Heart Association, Inc.