N-cadherin has a protective role in stable human atherosclerotic plaques: a morphological and immunohistochemical study

Atherosclerosis is a complex disease, the onset of which depends on various components of the vascular system, metabolism and immune system. It generates the fibro-fatty plaque or stable plaque characterized by accumulation of lipids in the intima of the arteries, a fibrous cap covering the atheroma core which may consists in lipid-laden cells (macrophages and vascular smooth muscle cells), proteoglycans, collagen, elastin, foam cells and, sometimes, cholesterol crystals needle-like clefts, fibrin and neovessels. The progression of the plaque leads to unstable atherosclerotic lesions. The result will be a large plaque, consisting of an evident lipid core surrounded by a fibrous cap, infiltrates of immunocompetent cells and calcium deposits. Advanced plaque is characterized by macrophages invasion and by the thinning of the fibrous cap. Progression of atherosclerotic plaque can lead to its rupture and result in the occlusion of an artery or in the formation of a thrombus. Apoptosis in the fibrous cap, rich in vascular smooth muscle cells and macrophages, and its subsequent weakening seems to be an important regulator of plaque stability. In our study, we collected specimens from stable atherosclerotic plaques in the right or left internal carotid artery of patients with clinical symptoms. Histology and histochemistry were performed in specimens for cell identification and detection of structural alterations. Immunohistochemical analysis related to caspase-3 and N-cadherin was performed in order to highlight the pro-survival role of N-cadherin against apoptosis in the stable atherosclerotic plaques. Our results showed that when expression of N-cadherin is evident and strong in the stable atherosclerotic plaques, apoptosis, expressed by caspase-3 immunostaining, is not detected, as reported by recent literature. The aim of our study was to acquire greater knowledge on the biological mechanisms related to plaque vulnerability in order to develop new therapies to maintain atherosclerotic plaque stability avoiding its rupture which could determine consequences such as thrombosis.