Adhesion molecules in nonrheumatic aortic valve disease: endothelial expression, serum levels and effects of valve replacement.

OBJECTIVES: We studied the expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and endothelial selectin (E-selectin) on aortic valve endothelium in patients undergoing valve replacement. We also assessed the relation between serum levels and endothelial expression and also the changes in serum levels following surgery. BACKGROUND: Nonrheumatic aortic valve disease is believed to be a degenerative condition. Increased tissue and soluble adhesion molecule levels are described in inflammatory conditions. METHODS: Aortic valves from 22 surgical (16 bicuspid, 6 tricuspid) and 6 autopsy (4 normal, 2 thickened) cases were studied by immunohistochemistry. Soluble adhesion molecules were measured in peripheral blood preoperatively, and at 6 and 18 months postoperatively, and compared with controls. RESULTS: The majority of the surgically removed tricuspid and bicuspid valves expressed adhesion molecules (E-selectin, 75% and 100%; ICAM-1, 75% and 80%; VCAM-1, 69% and 60%, respectively). The normal postmortem valves did not express these, while the diseased ones did. Endothelial expression of E-selectin correlated strongly with serum levels (r = 0.695, p = 0.004). Soluble E-selectin levels were significantly higher at baseline compared with controls (p = 0.017) and fell significantly at 18 months postoperatively (p = 0.005). CONCLUSIONS: Adhesion molecule expression on diseased valves supports an inflammatory component in "degenerative" aortic valve disease. The diseased valves may be the main source of elevated soluble E-selectin in this condition as blood levels correlate with endothelial expression and blood levels fall at 18 months postoperatively.

Early temporal expression of soluble cellular adhesion molecules in patients with unstable angina and subendocardial myocardial infarction.

Inflammation is increasingly considered to be involved in the pathogenesis of acute coronary syndromes. We documented persistent elevation in the levels of soluble ICAM-1 and soluble VCAM-1 and a decrease in the levels of soluble E-selectin in the first 72 hours of acute presentation in patients with unstable angina and subendocardial myocardial infarction.

Impact of intravenous nitroglycerin on pulsed Doppler indexes of left ventricular filling in acute anterior myocardial infarction.

BACKGROUND: Restrictive transmitral Doppler flow patterns are associated with heart failure in acute myocardial infarction (AMI). METHODS AND RESULTS: The objective of this study was to evaluate the effect of intravenous nitroglycerin on the transmitral pulsed Doppler patterns in patients with anterior AMI. Twenty-four patients with anterior AMI were randomly assigned to receive incremental intravenous nitroglycerin or placebo over a 16-minute period with change to the other arm after a washout period. Left ventricular filling was assessed with transmitral pulsed Doppler echocardiography. According to the baseline E/A ratio, patients were divided into a restrictive group (n = 17, E/A ratio > or =21.4) and a nonrestrictive group (n = 7, E/A <1.4). In the restrictive group after administration of nitroglycerin the E/A ratio decreased (1.9+/-0.7 to 1.1+/-0.2, P < .001), E-wave peak velocity decreased (71+/-10 to 60+/-9 cm/s, P < .01), and A-wave peak velocity increased (39+/-9 to 58+/-8 cm/s, P < .01 ). In the nonrestrictive group there were no significant changes after nitroglycerin infusion in the E/A ratio (1.1+/-0.2 to 0.8+/-0.1, not significant), peak E-wave velocity (55+/-4 to 47+/-6 cm/s), and peak A-wave velocity (49+/-8 to 52+/-8 cm/s). Deceleration time increased significantly in both groups after administration of nitroglycerin. Placebo did not result in significant changes in hemodynamic or Doppler parameters in either group. CONCLUSIONS: Intravenous nitroglycerin administration was associated with reversal of restrictive left ventricular diastolic filling pattern on pulsed wave Doppler in patients with anterior AMI.

Elevated levels of circulating soluble adhesion molecules in peripheral blood of patients with unstable angina.

We have demonstrated increased levels of the circulating soluble adhesion molecules (sCAMs), ICAM-1, VCAM-1, and E-selectin in patients with unstable angina compared with healthy controls. Our findings support the role of inflammation in clinically unstable coronary disease, and may indicate a potential role for measurement of peripheral sICAM levels as a marker for inflammatory activity in atherosclerotic plaque.

Elevated levels of circulating soluble adhesion molecules in patients with nonrheumatic aortic stenosis.

Increased serum levels of soluble adhesion molecules are found in various disorders of inflammatory or immunologic etiology. We found elevated levels of the soluble adhesion molecules ICAM-1, VCAM-1, and E-selectin in patients with nonrheumatic aortic stenosis, suggesting that inflammation may be important in the pathogenesis of this condition, which is generally believed to be degenerative.

Familial Hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome maps to a locus on chromosome 7q3.

We have mapped a disease locus for Wolff-Parkinson-White syndrome (WPW) and familial hypertrophic cardiomyopathy (FHC) segregating in a large kindred to chromosome 7 band q3. Although WPW syndrome and FHC have been observed in members of the same family in prior studies, the relationship between these two diseases has remained enigmatic. A large family with 25 surviving individuals who are affected by one or both of these conditions was studied. The disease locus is closely linked to loci D7S688, D7S505, and D7S483 (maximum two point LOD score at D7S505 was 7.80 at theta = 0). While four different FHC loci have been described this is the first locus that can be mutated to cause both WPW and/or FHC.