Expression of cell adhesion molecule T-cadherin in the human vasculature

Abstract

Alterations in expression of surface adhesion molecules on resident vascular and blood-derived cells play a fundamental role in the pathogenesis of cardiovascular disease. Smooth muscle cells (SMCs) have been shown to express T-cadherin (T-cad), an unusual GPIanchored member of the cadherin family of adhesion molecules. Particular relevance for T-cad in cardiovascular tissues is indicated by our present screen (immunoblotting) of human tissues and organs whereby highest expression of T-cad was found in aorta, carotid, iliac and renal arteries and heart. To explore the (patho)physiological role for T-cad in the vasculature we performed an immunohistochemical analysis of T-cad expression in normal human aorta and atherosclerotic lesions of varying severity. T-cad was present both in the intima and media and was expressed in endothelial cells (ECs), SMCs and pericytes, but not in monocytes/macrophages, foam cells and lymphocytes. In the adventitia T-cad was present in the wall of vasa vasorum and was expressed in ECs, SMCs and pericytes. T-cad was differentially expressed in SMCs from distinct vascular layers of normal aorta (for example, high in the subendothelial (proteoglycan) layer of the intima, low in the musculoelastic intimal layer and in the media), as well as at different stag-es of lesion progression. In SMCs there was an apparent inverse relationship between the intensities of T-cad and smooth muscle α-actin expression, this being most prominent in lesions. The findings suggest a phenotypeassociated expression of T-cad which may be relevant to control of the normal vascular architecture and its remodelling during atherogenesis.

Expression of adiponectin in choroidal tissue and inhibition of laser induced choroidal neovascularization by adiponectin

“…APN acts via two receptor isoforms, AdipoR1 and AdipoR2 [3]. AdipoR1 and AdipoR2 contain seven transmembrane domains, but are structurally and functionally different from G protein-coupled receptors [4][5][6][7][8][9][10].…”

Extracellular Cadherin repeat domains EC1 and EC5 of T‐cadherin are essential for its ability to stimulate angiogenic behavior of endothelial cells

“…T-cad is abundantly expressed in the vasculature, and accumulating data support a facilitatory role in the progression of pathological conditions associated with neovascularization. Up-regulation of T-cad has been shown to occur in vivo on vascular cells during atherosclerosis (15) and restenosis (16) and on endothelial cells from neovessels in lung metastases of different tumors (17) and metastatic hepatocellular carcinoma (18,19). Expression of T-cad in cultures of smooth muscle or endothelial cells correlated with cell-cycle progression and proliferation status (16,20).…”

Integrin‐linked kinase is an essential mediator for T‐cadherin‐dependent signaling via Akt and GSK3β in endothelial cells

“…T-cadherin (T-cad), an atypical member of the cadherin superfamily, is widely expressed in the cardio-vascular system. Expression of T-cad in vascular cells is markedly increased during atherosclerosis (1), restenosis after balloon angioplasty (2), and tumor neovascularization (3). Accumulating data support that T-cad participates in several processes (e.g., differentiation, migration, proliferation, and survival) that occur during vascular remodeling and angiogenesis.…”