Role of Cell Adhesion Molecules and Immune-Cell Migration in the Initiation, Onset and Development of Atherosclerosis

Abstract

Atherosclerosis is currently the leading factor of death in developed countries. It is now recognized as a chronic immune-inflammatory disease, whose initial stages involve the interaction of leukocytes with the endothelial monolayer. The initial stage of atherosclerosis requires the interplay of various cell adhesion molecules and immune cells to trigger leukocyte and lymphocyte migration from the circulating blood into the arterial intima. Studies have unveiled the role of inflammatory mediators in the initiation, onset and progression of the disease. During the last few years we have gained a greater understanding of the mechanism that modulates monocyte, macrophage and T cell infiltration, the role these cells play in the atherosclerotic lesion, in the formation of the fibrous plaque formation with the consequent narrowing of the arteries and the mechanisms that lead to plaque rupture and the formation of thrombi and emboli. This review talks about the leukocyte recruitment in early atherosclerosis, the formation of the plaque, and the mechanisms that lead to thrombosis in advanced atherosclerosis. Finally, we discuss the potential for novel therapies to treat this disease.

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications

“…Calcification and angiogenesis are also common characteristics of advanced lesions and thrombosis (62).…”

“…Formation and aggregation of foam cells results in "fatty streaks" and production of a necrotic core. The center of the core contains an abundance of apoptotic and necrotic cells (62).…”

Uso de carmustina associada a nanoemulsões ricas em colesterol (LDE) para tratamento da aterosclerose induzida em coelhos

“…Essas células rolam ao longo da superfície endotelial através da ligação com as selectinas P e E, moléculas de adesão. A fixação firme de monócitos e linfócitos T ao endotélio é mediada pela interação da molécula de adesão intercelular-1 (ICAM-1) (Chi & Melendez, 2007), molécula de adesão celular vascular-1 (VCAM-1), e proteína quimioatraente de monócitos-1 (MCP-1) (Chi & Melendez, 2007;Libby et al, 2010;van Diepen et al, 2013;Legein et al, 2013).…”

“…Através desses receptores os macrófagos fagocitam as partículas de LDL oxidadas, as quais se acumulam no seu citoplasma e formam as células espumosas (Chi & Melendez, 2007;Badimon et al, 2011;Hansson & Hermansson, 2011;Legein et al, 2013). Nessas lesões, os macrófagos podem secretar citocinas pró-inflamatórias, como a interleucina-1β (IL-1β) e o fator de necrose tumoral-α (TNF-α), assim como os linfócitos T que, secretam interferon-ɣ (IFN-ɣ), fator de necrose tumoral α e β e interleucina-1 (Ross, 1999;Hansson, 2005), as quais amplificam a resposta inflamatória local, promovendo o recrutamento de mais células e LDL oxidadas, contribuindo para a aterogênese (Libby et al, 2011;Bentzon et al, 2014).…”

“…A proliferação celular adicional sobre os ateromas produzirá assim as placas fibrosas (Cotran et al, 2000;Plutzky, 2003;Chi & Melendez, 2007). Essa proliferação celular contínua pode levar a deposição celular e desencadear eventos clínicos como isquemia cardíaca e infarto do miocárdio, decorrentes da oclusão arterial (Libby et al, 2011).…”