Satoko Wada

Association between hemoglobin scavenger receptor and heme oxygenase–1–related anti-inflammatory mediators in human coronary stable and unstable plaques

Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that is induced by intraplaque hemorrhage and degrades free heme and releases ferrous iron, which is rapidly sequestered by ferritin. In vitro studies have shown that binding of hemoglobin to hemoglobin scavenger receptor (CD163) induces HO-1 and the anti-inflammatory mediator interleukin (IL)-10. We immunohistochemically examined the relationship between CD163 expression in macrophages and intraplaque hemorrhage, HO-1, IL-10, and ferritin using coronary atherectomy specimens from patients with stable (SAP) or unstable angina pectoris (UAP). A total of 67 patients underwent atherectomy for SAP (n = 33) or UAP (n = 34). Samples were stained with antibodies against smooth muscle cells, macrophages, glycophorin-A (a protein specific to erythrocyte membranes), CD163, HO-1, IL-10, and ferritin. To identify cell types of HO-1-positive cells, double immunostaining was also performed. Double immunostaining for HO-1 and macrophages revealed that the vast majority of HO-1-positive cells were macrophages. Morphometric analysis demonstrated that CD163-positive macrophage score and the percentage of glycophorin-A-, HO-1-, IL-10-, and ferritin-positive areas were significantly higher in UAP than in SAP patients (CD163, P < .005; glycophorin-A, P < .0001; HO-1, P < .0001; IL-10, P < .005; ferritin, P = .0001). Moreover, CD163-positive macrophage score was positively associated with the percentage of glycophorin-A-, HO-1-, IL-10-, and ferritin-positive areas (glycophorin-A, r = 0.60, P < .0001; HO-1, r = 0.67, P < .0001; IL-10, r = 0.45, P < .0005; ferritin, r = 0.61, P < .0001). These findings suggest that enhanced expression of HO-1 and HO-1-related atheroprotective molecules plays an important role in exerting anti-inflammatory, antioxidant, and scavenging functions, which could contribute to plaque stabilization.

PERSISTENT ELEVATED LEVELS OF MRP 8/14 AND CARDIOVALCULAR EVENTS AFTER DES IMPLANTATION IN PATIENTS WITH STABLE ANGINA PECTORIS

Background: Myeloid-related protein (MRP) 8/14, a heterodimer of S100A8 (10.8 kD) and S100A9 (13.2 kD), is expressed in activated human neutrophils and macrophages. The present study was designed to investigate the time-course of changes in serum MRP-8/14 levels in patients with stable angina pectoris (SAP) undergoing drug-eluting stent (DES) implantation. Furthermore, we investigated whether serum MRP-8/14 levels predict future cardiovascular events.

INCREASED EXPRESSION AND PLASMA LEVELS OF NEOPTERIN ARE CLOSELY RELATED TO AORTIC VALVE STENOSIS IN PATIENTS WITH HEMODIALYSIS

Aortic valve stenosis (AS) occurs with increased frequency in hemodialysis (HD) patients and could contribute to the excess cardiovascular mortality. However, little is known about differences in progression of the AS process between HD and non-HD patients. Neopterin, a by-product of the guanosine

CAUSES OF DEATH IN ASYMPTOMATIC AORTIC STENOSIS IN JAPAN

Results: Forty three of the 95 asymptomatic and 16 of the 24 symptomatic AS died (p=ns). The number of cardiovascular death was not different between asymptomatic and symptomatic AS. Notably, there were 6 sudden deaths in asymptomatic AS. Moreover, the timing of sudden death was not different between asymptomatic and symptomatic AS (35±24vs35±30months, p=ns) though the number was more frequent in symptomatic AS (p=0.028).