Levels of soluble adhesion molecules in various clinical presentations of coronary atherosclerosis.
ABSTRACT Adhesion molecules play an important role in the development and course of coronary atherosclerosis. In this study, soluble forms of vascular cell adhesion molecule (VCAM-1) intercellular adhesion molecule-1 (ICAM-1), E-selectin and P-selectin were evaluated in patients with various clinical presentations of coronary atherosclerosis and compared them to those with angiographically documented normal coronary arteries. Venous plasma samples were collected from 43 patients with acute myocardial infarction (AMI), 45 with unstable angina pectoris (UAP), 34 with stable angina pectoris (SAP) and 29 subjects with normal coronary arteries (control). The VCAM-1 level was significantly higher in patients with AMI (mean +/- SEM; 799.8 +/- 26.3 ng/ml) than those with UAP (644.2 +/- 26.7 ng/ml) and SAP (526 +/- 32.5 ng/ml) and controls (270 +/- 26.8 ng/ml). In patients with UAP, VCAM-1 was found to be significantly elevated as compared to the SAP group and controls. VCAM-1 level was also higher in SAP group than the controls. Serum levels ICAM-1 were similar among patients with AMI (424.1 +/- 15.2 ng/ml), UAP (403 +/- 12.3 ng/ml) and SAP (381.2 +/- 16.2 ng/ml); however, levels of ICAM-1 was significantly elevated in these groups as compared to the controls (244.3 +/- 11). The mean level of E-selectin was not different in AMI and UAP groups (47.2 +/- 2.2 vs. 42.6 +/- 2.1 ng/ml; respectively). However, it was significantly higher in acute coronary syndrome groups as compared to SAP (33.4 +/- 2.3 ng/ml) and control subjects (30.7 +/- 1.9 ng/ml). Serum levels of E-selectin were similar in SAP group and controls. For P-selectin, no significant difference was observed between AMI and UAP groups (187.5 +/- 7.2 vs. 181.7 +/- 4.7 ng/ml; respectively), however, it was significantly higher in both groups as compared to SAP group (146.1 +/- 7.4 ng/ml) and controls (108 +/- 6.6 ng/ml). Serum level of P-selectin was significantly higher in patients with SAP than the control group. In conclusion, determination of serum VCAM-1, E-selectin and P-selectin levels seems more useful for detecting coronary plaque destabilization.
04/2012; , ISBN: 978-953-51-0561-9
Article: Elevated plasma free fatty acids increase cardiovascular risk by inducing plasma biomarkers of endothelial activation, myeloperoxidase and PAI-1 in healthy subjects.[show abstract] [hide abstract]
ABSTRACT: CVD in obesity and T2DM are associated with endothelial activation, elevated plasma vascular inflammation markers and a prothrombotic state. We examined the contribution of FFA to these abnormalities following a 48-hour physiological increase in plasma FFA to levels of obesity and diabetes in a group of healthy subjects. 40 non-diabetic subjects (age = 38 +/- 3 yr, BMI = 28 +/- 1 kg/m2, FPG = 95 +/- 1 mg/dl, HbA1c = 5.3 +/- 0.1%) were admitted twice and received a 48-hour infusion of normal saline or low-dose lipid. Plasma was drawn for intracellular (ICAM-1) and vascular (VCAM-1) adhesion molecules-1, E-selectin (sE-S), myeloperoxidase (MPO) and total plasminogen inhibitor-1 (tPAI-1). Insulin sensitivity was measured by a hyperglycemic clamp (M/I). Lipid infusion increased plasma FFA to levels observed in obesity and T2DM and reduced insulin sensitivity by 27% (p = 0.01). Elevated plasma FFA increased plasma markers of endothelial activation ICAM-1 (138 +/- 10 vs. 186 +/- 25 ng/ml), VCAM-1 (1066 +/- 67 vs. 1204 +/- 65 ng/ml) and sE-S (20 +/- 1 vs. 24 +/- 1 ng/ml) between 13-35% and by > or = 2-fold plasma levels of myeloperoxidase (7.5 +/- 0.9 to 15 +/- 25 ng/ml), an inflammatory marker of future CVD, and tPAI-1 (9.7 +/- 0.6 to 22.5 +/- 1.5 ng/ml), an indicator of a prothrombotic state (all p < or = 0.01). The FFA-induced increase was independent from the degree of adiposity, being of similar magnitude in lean, overweight and obese subjects. An increase in plasma FFA within the physiological range observed in obesity and T2DM induces markers of endothelial activation, vascular inflammation and thrombosis in healthy subjects. This suggests that even transient (48-hour) and modest increases in plasma FFA may initiate early vascular abnormalities that promote atherosclerosis and CVD.Cardiovascular Diabetology 02/2010; 9:9. · 3.35 Impact Factor
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ABSTRACT: To examine whether the psychological traits of hopelessness and depressive symptoms are related to endothelial dysfunction. Data are derived from a subsample of 434 respondents in the 2001 to 2003 Chicago Community Adult Health Study, a population-based survey designed to study the impact of psychological attributes, neighborhood environment, and socioeconomic circumstances on adults aged ≥18 years. Circulating biomarkers of endothelial dysfunction, including e-selectin, p-selectin, and soluble intercellular adhesion molecule-1 (s-ICAM1) were obtained from serum samples. Hopelessness was measured by responses to two questions, and depressive symptoms were measured by an 11-item version of the Center for Epidemiological Studies Depression scale. Multivariate regression models tested whether continuous levels of the biomarkers (natural log transformed) were associated with levels of hopelessness and depressive symptoms separately and concurrently. In age- and sex-adjusted models, hopelessness showed significant positive linear associations with s-ICAM1. In contrast, there was no significant linear association between hopelessness and e-selectin and p-selectin. Adjustment for clinical risk factors, including systolic pressure, chronic health conditions, smoking, and body mass index, did not substantively alter these associations. Results from similar models for depressive symptoms did not reveal any association with the three biomarkers of endothelial dysfunction. The associations between hopelessness and e-selectin and s-ICAM1 were robust to the inclusion of adjustments for depressive symptoms. Negative psychosocial traits may influence cardiovascular outcomes partially through their impact on the early stages of atherosclerosis, and specific psychosocial traits, such as hopelessness, may play a more direct role in this process than overall depressive symptoms.Psychosomatic Medicine 05/2010; 72(7):613-9. · 3.97 Impact Factor