Objective-To clarify circulating microparticles (MP) relationships with preclinical atherosclerosis. Methods and Results-In 216 subjects without cardiovascular disease, we assessed: (1) annexin V-positive, plateletderived, endothelium-derived and leukocyte-derived circulating MP by capture on annexin V, anti-GPIb, anti-CD105, and anti-CD11a antibody-coated wells, respectively; (2) Framingham risk, metabolic syndrome, and low-grade inflammation by risk factors measurement including hsCRP; and (3) subclinical atherosclerosis by ultrasound examination of carotid, abdominal aorta, and femoral arteries. Number of sites with plaque ranged from 0 to 3 and plaque burden was classified into 0 to 1 or 2 to 3 sites disease.

BackgroundPostulating that serotonin (5-HT), released from smoking-activated platelets could be involved in smoking-induced vascular modifications, we studied its catabolism in a series of 115 men distributed as current smokers (S), never smokers (NS) and former smokers (FS) who had stopped smoking for a mean of 13 years.Methodology/Principal Findings5-HT, monoamine oxidase (MAO-B) activities and amounts were measured in platelets, and 5-hydroxyindolacetic acid (5-HIAA)—the 5-HT/MAO catabolite—in plasma samples. Both platelet 5-HT and plasma 5-HIAA levels were correlated with the 10-year cardiovascular Framingham relative risk (P<0.01), but these correlations became non-significant after adjustment for smoking status, underlining that the determining risk factor among those taken into account in the Framingham risk calculation was smoking. Surprisingly, the platelet 5-HT content was similar in S and NS but lower in FS with a parallel higher plasma level of 5-HIAA in FS. This was unforeseen since MAO-B activity was inhibited during smoking (P<0.00001). It was, however, consistent with a higher enzyme protein concentration found in S and FS than in NS (P<0.001). It thus appears that MAO inhibition during smoking was compensated by a higher synthesis. To investigate the persistent increase in MAO-B protein concentration, a study of the methylation of its gene promoter was undertaken in a small supplementary cohort of similar subjects. We found that the methylation frequency of the MAOB gene promoter was markedly lower (P<0.0001) for S and FS vs. NS due to cigarette smoke-induced increase of nucleic acid demethylase activity.Conclusions/SignificanceThis is one of the first reports that smoking induces an epigenetic modification. A better understanding of the epigenome may help to further elucidate the physiopathology and the development of new therapeutic approaches to tobacco addiction. The results could have a larger impact than cardiovascular damage, considering that MAO-dependent 5-HT catabolism is also involved in addiction, predisposition to cancer, behaviour and mental health.

The aggregation and disaggregation behaviors of red blood cells were investigated in 17 nonnotensive and 21 hypertensive subjects with a laser reflectometry technique, and simultaneous measurements were taken of blood viscosity with a coaxial viscometer. Increased red blood cell aggregation (26%, p< 0.001) and disaggregation shear rate (20%, p<0.01) and shear stress (18%, p<0.01) were observed in hypertensive subjects when compared with nonnotensive subjects. Similar elevations in hypertensive subjects were found when the hematocrit was adjusted to 40%. Variation of red blood cell concentration caused the red blood cell disaggregation shear rate to change in an opposite direction but did not modify red blood cell aggregability and disaggregation shear stress. The increase of the reversible aggregation of red blood cells was associated with higher fibrinogen and plasma protein concentrations in hypertension. An increase in red blood cell aggregability and in the shear resistance of red blood cell aggregates may play a role in the development of the cardiovascular complication in hypertension. The quantification of red blood cell disaggregation shear stress, which represents the hydrodynamic force required to disperse the aggregates, may provide a useful parameter for clinical investigations. 1 The aggregation of RBC is a reversible phenomenon that occurs with macromolecules bridging the membranes of adjacent cells, and it is influenced by 1) the shearing force of blood, 2) the properties of erythrocytes (concentration, deformability, surface charge, and shape), and 3) the bridging force of high molecular weight plasma proteins.2 " 4 This phenomenon represents an equilibrium between adhesive forces (macromolecules bridging force), repulsive forces (electrical charges on RBC surface), 5 and mechanical forces (shear stress). -6 When the adhesive force is increased in pathological conditions, the shear stress required to break up RBC aggregates would become elevated.In hypertension, increases of red blood cell aggregation were largely extrapolated from blood viscosity measurements at low shear rates. 7 -11 In contrast, few studies have used direct quantitative methods to evaluate red blood cell aggregation in hypertension.12 Relatively little data are available on the shear stress needed to break up the aggregated RBC in normal and patho- A preliminary report of this work was presented at the 64th Scientific Sessions of the American Heart Association, Anaheim, Calif., November 11-14, 1991, and was published in abstract form (Razavian SM, Levenson J, Del-Pino M, Simon A: The shear stress for disaggregating red blood cells is increased in hypertension. Circulation 1991;84:II-53).Supported by grants from the Institut National de la Santi et de la Recherche Medicale and the Institut Jean Merlen.Address for reprints: Dr. Jaime Levenson, Centre de M6decine Preventive Cardiovasculaire, H6pital Broussais, 96 Rue Didot, 75674 Paris CEDEX 14, France.Received May 7,1991; accepted in revised form April 13, 1992. logical cond...

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While cardiac output is increased and systemic vascular resistance is decreased in active acromegaly, direct measurement of brachial artery haemodynamics showed lower regional blood flow and increased local resistance relative to healthy controls. These results suggest a heterogeneous distribution of cardiac output in acromegaly.

The diameter, blood velocity, and blood flow of the brachial artery were evaluated with a pulsed-Doppler apparatus before and after wrist occlusion in 16 normocholesterolemic and 27 hypercholesterolemic male subjects of similar age and body mass index. Before occlusion, no hemodynamic differences were observed between the two groups. Occlusion significantly reduced blood velocity and blood flow in the two groups (p< 0.001), but such reductions were not different between hypercholesterolemic and normocholesterolemic groups. Occlusion decreased the arterial diameter in the hypercholesterolemic group only (p<0.001), and absolute diameter changes after occlusion were significantly different between the two groups (p< 0.001). No correlation was found between the change in arterial diameter after occlusion and the baseline diameter before occlusion in the normocholesterolemic and hypercholesterolemic population overall. Absolute and percent diameter changes after occlusion were correlated with total cholesterol (r=-0.73, r= -0.72; p<0.001) and with low density lipoprotein (LDL) cholesterol (r=-0.68, r=-0.69;/><0.001) in the normocholesterolemic and hypercholesterolemic population overall, respectively. These findings indicate that the low-flow state induces a reduction in large-artery diameter in the hypercholesterolemic but not in the normocholesterolemic state and is closely related to the degree of elevation of blood cholesterol and of its LDL fraction. (Arteriosclerosis and Thrombosis 1991;11:161-166) H ypercholesterolemia is recognized as a major cardiovascular risk factor, 1 but the determination of its dominant hemodynamic changes associated with early lesion development remains unclear.2 Recent observations of aortas isolated from animals fed cholesterol-rich diets have shown several alterations in vascular reactivity, such as an augmented contractile responsiveness to certain vasoactive substances.3 These alterations were reversible with a switch to cholesterol-poor diets, 4 and it has been speculated that changes in endothelial function might play an important role in their mechanisms. 5 The objective of our study was to investigate in vivo the influence of hypercholesterolemia on large-artery reactivity in humans. The bra-

Since Ca2+ ions seem to directly participate in the control of erythrocyte membrane structure and deformability and because cell Ca 2+ metabolism has been repeatedly proposed to be modified in hypertension, the intracellular calcium ion concentration (

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