ABSTRACT
The signaling system of phosphoinositides (PI) is involved in a variety of cell and tissue functions, including membrane trafficking, ion channel activity, cell cycle, apoptosis, differentiation, and cell and tissue polarity. Recently, PI and related molecules, such as the phosphoinositide-specific phospholipases C (PI-PLCs), main players in PI signaling were supposed to be involved in inflammation. Besides the control of calcium levels, PI-PLCs contribute to the regulation of phosphatydil-inositol bisphosphate metabolism, crucial in cytoskeletal organization. The expression of PI-PLCs is strictly tissue specific and evidences suggest that it varies under different conditions, such as tumor progression or cell activation. In a previous study, we obtained a complete panel of expression of PI-PLC isoforms in human umbilical vein endothelial cells (HUVEC), a widely used experimental model for endothelial cells. In the present study, we analyzed the mRNA concentration of PI-PLCs in lipopolysaccharide (LPS)-treated HUVEC by using the multiliquid bioanalyzer methodology after 3, 6, 24, 48, and 72 h from LPS administration. Marked differences in the expression of most PI-PLC codifying genes were evident.
Subject(s)
Gene Expression Regulation, Enzymologic , Lipopolysaccharides/immunology , Phosphoinositide Phospholipase C/genetics , Cell Line , Down-Regulation , Gene Expression , Human Umbilical Vein Endothelial Cells/enzymology , Humans , Inflammation/chemically induced , Phosphatidylinositols/immunology , Phosphoinositide Phospholipase C/metabolism , RNA, Messenger/analysis , Signal TransductionABSTRACT
BACKGROUND: Epidemiological studies have shown that increased arterial stiffness and wave reflections, major determinants of systolic and pulse pressure, are associated with morbidity and mortality. Therapeutic trials based on cardiovascular mortality have recently shown that reduction of systolic blood pressure (SBP) requires normalization of both large-artery stiffness and wave reflections. AIMS: To compare the antihypertensive effects of the very-low-dose combination of perindopril (2 mg) and indapamide (0.625 mg) (one or two tablets per day) with the beta-blocking agent atenolol (50 mg; one or two tablets per day) in order to determine whether the combination decreased SBP and pulse pressure more than did atenolol, and whether this decrease occurred in relation to a reduction in arterial stiffness [aortic pulse wave velocity (PWV)] or a decrease in the intensity of, or delay in, wave reflections (augmentation index, measured by applanation tonometry) or a combination of both. MATERIAL AND METHODS: This was a double-blind randomized study in 471 individuals with essential hypertension followed for 12 months. Arterial pressure was measured in the brachial artery (mercury sphygmomanometer) and in the carotid artery (applanation tonometry). RESULTS: For the same reduction in diastolic blood pressure (DBP), the combination of perindopril and indapamide decreased brachial SBP and pulse pressure significantly more than did atenolol (adjusted differences between groups -6.2 +/- 1.5 and -5.5 +/- 1.0 mmHg, respectively; P < 0.001). This difference was even more pronounced for the carotid than for the brachial artery. Whereas both antihypertensive agents similarly decreased PWV, only the combination significantly attenuated wave reflections. CONCLUSION: Normalization of SBP, pulse pressure and arterial function--a haemodynamic profile known to improve survival significantly in hypertensive populations at high cardiovascular risk--was achieved to a greater extent with a very-low-dose combination of perindopril and indapamide than with atenolol.
