The influence of hypercholesterolemia on the components of purinergic signaling in mouse brain endothelial cells

• Published in: Folia neuropathologica Vol. 56; no. 3; p. 248
• Main Authors: Czuba, E, Pelikant-Malecka, I, Smolenski, T, Steliga, A, Waskow, M, Morys, J, Kowianski, P
• Format: Journal Article
• Language: English
• Published: Warsaw Termedia sp. z o.o 01.01.2018
• Subjects: Adenine; Arteriosclerosis; Cholesterol; Cytokines; Diabetes mellitus; Endothelial cells; Energy metabolism; Enzymatic activity; Enzymes; Glial cells; Glycolysis; Hypercholesterolemia; Inflammation; Ischemia; Metabolic disorders; Microglia; Neuronal-glial interactions; Nucleotides; Plaques; Stroke
• ISSN: 1641-4640; 1509-572X

Current research proves that the occurrence and development of hypercholesterolemia correlate with a series of pathological changes such as diabetes mellitus, atherosclerosis and hypertension, which in turn lead to ischemic stroke, neurodegenerative changes and brain damages. According to the various reports, the main purinergic signaling pathways play a crucial role in controlling the functional integrity of neurons, glial cells and vascular endothelial cells in the CNS. Among the components of the purinergic system, adenine nucleotides play a major role in the inflammatory processes. ATP participates in energy metabolism and has pro-inflammatory activity by stimulating microglia and increasing the release of pro-inflammatory cytokines. The relationship between hypercholesterolemia and the numerous pathological changes that occur in metabolic disorders and brain damages is still unclear. For this reason, we used in our study wildtype C57/BL6 and LDLR–/–/Apo E–/– double-knockout mice to test their role in hypercholesterolemia in the brain. The mutation is associated with elevated plasma cholesterol level and develops atherosclerotic plaques at varying stages. The obtained results allow to confirm the increase activity of e-NTPDase, ecto-5’-NT and eADA enzymes. There were no differences in the intracellular concentration of adenine nucleotides and glycolytic function. The increase of enzymes activity with the unchanged concentration of adenine nucleotides and glycolytic function may be the manifestation of a compensatory mechanism that maintains the energy metabolism of endothelial cells at a constant level in the brain. Therefore, regulation of the inflammatory response by modulation of the extracellular enzymatic activity may be a new therapeutic strategy for metabolic disorders and brain damages.