Unique Sensitivities to Cytokine Regulated Expression of Adhesion Molecules in Human Heart-Derived Endothelial Cells

Abstract

The expression of adhesion molecules by endothelial cells is crucial in many inflammatory processes and plays an active role in the development of reperfusion injury, acute and chronic rejection. The expression of adhesion molecules in different parts of the coronary tree to cytokine stimulation is not known. We describe here a detailed study of the effects of the inflammatory cytokines TNFalpha and IL-1beta on the expression of adhesion molecules vascular cell adhesion molecule-1 (VCAM-1), E-selectin and intracellular cell adhesion molecule-1 (ICAM-1) on human aortic root (HAEC), coronary artery (HCAEC) and heart microvascular (HHMEC)) endothelial cells in culture, using flow cytometry. We found constitutive levels of both VCAM-1 and E-Selectin on HCAEC and HHMEC (approximately 20%) which were significantly higher compared to HAEC (approximately 3%). There was an extreme sensitivity of HCAEC and HHMEC to 0.002 ng/ml TNFalpha: (VCAM-1 approximately 40%, E-Selectin approximately 25%) respectively, compared to HAEC (VCAM-1 approximately 5%, E-selectin approximately 5%). IL-1beta showed a similar pattern of expression at low doses (5 U/ml), but was less potent. We also observed prolonged expression of these adhesion molecules, especially on the HHMEC (>48 hours) compared to HAEC. There was also increased binding of peripheral blood mononuclear cells (PBMC) to both non-stimulated and TNFalpha stimulated HCAEC and HHMEC compared to HAEC. This data suggest that endothelial cells in different regions of the coronary tree express different patterns of basal and cytokine-stimulated adhesion molecule expression.

Plakophilin-2 and the migration, differentiation and transformation of cells derived from the epicardium of neonatal rat hearts

“…The presence of intercellular junctions including their associated molecules was discovered in a population of non-myocytes that include endothelial and valvular interstitial cells (VICs) (Noria et al, 1999, Xu et al, 2011, Noria et al, 2004, Lester et al, 1988, Mulholland and Gotlieb, 1996, Latif et al, 2006, Taylor et al, 2003, Chester and Taylor, 2007, McDouall et al, 2001, Latif et al, 2005, Filip et al, 1986, Lupu and Simionescu, 1985, Dejana et al, 2009, Grazia Lampugnani et al, 2003, Lampugnani et al, 1992). The expression of adherens junction molecules including PKP2 within this junction - a protein traditionally located within the desmosome - have also been detected in VICs (Barth et al, 2009).…”

Vascular Inflammation in Aging

“…TNF-α is known to stimulate vascular NAD(P)H oxidases [27], the activity of which was shown to increase in aged coronary vessels and aorta [18] inactivating endothelium-derived NO. In addition, TNF-α and other pro-inflammatory cytokines may upregulate the expression of adhesion molecules [28], promote thrombus formation and induce the production of several cytokines in endothelial cells, including IL-6 as well as various chemokines [29]. Increased vascular tissue levels of TNF-α are also likely to contribute to the enhanced endothelial apoptosis in aged coronary arteries [3], which may represent an important link between aging-induced vascular inflammation, endothelial injury and plaque formation.…”

Human microvascular endothelial cells from different fetal organs demonstrate organ-specific CAM expression

“…Many human vascular diseases are restricted to specific types of vessels [8], and consequently the ECs may differ not only in respect to small versus large vessels but also between organs of the same individual. To date, in vitro research of the function of human ECs has been largely 0014-4827/$ -see front matter D 2005 Elsevier Inc. All rights reserved.…”