Circulating microparticles may influence early carotid artery remodeling.

OBJECTIVES: To test associations of circulating microparticles with large artery remodeling before atherosclerosis is detectable. METHODS: In 232 untreated symptom-free individuals, we measured microparticles of various cellular origins (platelet, endothelial and leukocyte) by specific anti-GPIb (glycoprotein Ib), anti-cluster of differentiation (CD) 105 and anti-CD11a antibodies, and common carotid artery intima-media thickness (IMT), internal and external diameters by ultrasound. RESULTS: Except for CD105 microparticles with IMT to lumen ratio (IMT/D, P < 0.05), microparticles correlated with no carotid dimensions. Significant interactions existed between each microparticle type and IMT on internal and external diameters (GPIb, P < 0.01; CD105 and CD11a microparticles P < 0.001) consisting of lower trend in increased diameter with increasing IMT in individuals with high than in those with low microparticle level (according to the median) of each origin. As a result, individuals within the third IMT tertile had lower internal diameter in the presence of high than in the presence of low level of GPIb, CD105 or CD11a microparticles (P = 0.001, <0.05 or 0.01, respectively), and lower external diameter in the presence of high than in the presence of low level of GPIb and CD11a microparticles (P = 0.001 and 0.01). Also, individuals within third IMT tertile exhibited positive correlations of IMT with CD105 and CD11a microparticles (P < 0.05), negative correlations of internal diameter with GPIb (P < 0.05), CD105 (P < 0.05) and CD11a microparticles (P < 0.01) and of external diameter with GPIb and CD11a microparticles (P < 0.05), and positive correlations of IMT/D with CD105 and CD11a microparticles (P < 0.001). CONCLUSION: Increased levels of leukocyte and endothelial-derived microparticles are associated with carotid inward remodeling in individuals with the greatest IMT before atherosclerosis is detectable.

Correction of carotid intima-media thickness for adaptive dependence on tensile stress: implication for cardiovascular risk assessment.

PURPOSE: Early artery wall-thickening detected by ultrasound-assessed increased carotid intima-media thickness (IMT) may reflect atherosclerosis or represent an adaptive response to keep homeostasis tensile stress that is related inversely to wall thickness by Laplace's equation. We attempted to discriminate between both mechanisms by correcting IMT for its inverse association with tensile stress. METHODS: Common carotid IMT and lumen diameter (D) where determined in 40 healthy controls and 119 never-treated asymptomatic patients with >or=1 traditional cardiovascular risk factor. The cross-sectional area (CSA) was calculated as pi x IMT x (IMT + D). Tensile stress was approximated by [mean blood pressure x (D/2 x IMT)], and wall shear stress by [(blood viscosity) x 4 x (mean blood velocity/D)]. Inverse regression line relating IMT and tensile stress in controls (p < 0.001) was used as a reference to determine in an individual at-risk patient the IMT deviation, defining DeltaIMT from the regression line of controls at the measured patient's tensile stress. RESULTS: DeltaIMT correlated positively with age (p < 0.05), body mass index (p < 0.05), blood pressure (p < 0.001), and glucose (p < 0.001). In multivariate analysis, DeltaIMT was independently associated with age (p < 0.01), male gender (p < 0.001), and blood pressure (p < 0.001). IMT showed positive association with age (p < 0.001) but not with other risk factors. Also, DeltaIMT, like CSA, correlated positively with tensile stress (p < 0.001) and negatively with wall shear stress (p < 0.05, p < 0.01), whereas IMT correlated negatively with tensile stress (p < 0.001) but not with wall shear stress. CONCLUSION: Correcting IMT for adaptive association with tensile stress may give more strength to carotid evaluation for assessing cardiovascular risk.

Endothelial microparticles in diseases.

Microparticles are submicron vesicles shed from plasma membranes in response to cell activation, injury, and/or apoptosis. The measurement of the phospholipid content (mainly phosphatidylserine; PSer) of microparticles and the detection of proteins specific for the cells from which they are derived has allowed their quantification and characterization. Microparticles of various cellular origin (platelets, leukocytes, endothelial cells) are found in the plasma of healthy subjects, and their amount increases under pathological conditions. Endothelial microparticles (EMP) not only constitute an emerging marker of endothelial dysfunction, but are also considered to play a major biological role in inflammation, vascular injury, angiogenesis, and thrombosis. Although the mechanisms leading to their in vivo formation remain obscure, the release of EMP from cultured cells can be caused in vitro by a number of cytokines and apoptotic stimuli. Recent studies indicate that EMP are able to decrease nitric-oxide-dependent vasodilation, increase arterial stiffness, promote inflammation, and initiate thrombosis at their PSer-rich membrane, which highly co-expresses tissue factor. EMP are known to be elevated in acute coronary syndromes, in severe hypertension with end organ damage, and in thrombotic thrombocytopenic purpura, all conditions associated with endothelial injury and pro-thrombotic state. The release of EMP has also been associated with endothelial dysfunction of patients with multiple sclerosis and lupus anticoagulant. More recent studies have focused on the role of low shear stress leading to endothelial cell apoptosis and subsequent EMP release in end-stage renal disease. Improved knowledge of EMP composition, their biological effects, and the mechanisms leading to their clearance will probably open new therapeutic approaches in the treatment of atherothrombosis.