CD36 is a multi-ligand scavenger receptor present on the surface of a number of cells such as platelets, monocytes/macrophages, endothelial and smooth muscle cells. Monocyte/macrophage CD36 has been shown to play a critical role in the development of atherosclerotic lesions by its capacity to bind and endocytose oxidized low density lipoproteins (OxLDL), and it is implicated in the formation of foam cells. However, the significance of CD36 in atherosclerosis has recently been called into question by different studies, and therefore its exact role still needs to be clarified. The aim of this article is to carefully review the importance of CD36 as an essential component in the pathogenesis of atherosclerosis. © 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.Keywords: CD36; Vascular; Monocyte/macrophages; OxLDL; Atherosclerosis Atherosclerosis is a progressive chronic inflammatory disease characterised by a gradual thickening and hardening of arteries that ultimately leads to a reduction in the lumen diameter and potentially to ischemia following plaque rupture. A first stage of the disease is the presence of dysfunctional endothelial cells (EC) which via activated adhesion molecules and expressed chemokines recruit circulating monocytes and a subpopulation of lymphocytes (CD4/CD8) into the intima. Endothelial dysfunction may be induced by oxidized low density lipoproteins (OxLDL). Indeed, LDL when infiltrating into the intima can be readily oxidized by resident macrophages or endothelial cells. Moreover, C-reactive protein (CRP) and OxLDL can act synergistically to increase monocytes inflammatory properties (through MCP-1, PGE2, MMP-1 production) and attract further circulating monocytes through the release of MCP-1 to adhere to the activated dysfunctional endothelial cells and extravasate to the intima to scavenge OxLDL [1]. One of the involvements of CD36 in lesion development is its ability to bind and endocytose OxLDL into macrophages, as a scavenger receptor, and ultimately be implicated in the differentiation of resident macrophages into foam cells that constitute the atherosclerotic lesion core.CD36 is an 88-kD membrane glycoprotein that was first identified on monocytes by monoclonal antibody OKM5 [2] and then subsequently isolated from blood platelets [3,4]. This membrane glycoprotein is expressed by many celltypes including microvasculature endothelial [5] and smooth muscle cells (SMC) [6]. Functional and structural characterisation showed CD36 to be a member of the scavenger receptor class B family with a capacity to bind OxLDL as well as various other ligands. The importance of monocytic CD36 in the initiation and perpetuation of atherosclerotic lesions was shown over this past decade by its effect in significantly reducing the size of vascular lesions when

Background & Aims: Hints, Histidine triad nucleotide-binding proteins, are adenosine monophosphate-lysine hydrolases of uncertain biological function. Here we report the characterization of human Hint2.

A few signaling pathways are driving the growth of hepatocellular carcinoma. Each of these pathways possesses negative regulators. These enzymes, which normally suppress unchecked cell proliferation, are circumvented in the oncogenic process, either the over-activity of oncogenes is sufficient to annihilate the activity of tumor suppressors or tumor suppressors have been rendered ineffective. The loss of several key tumor suppressors has been described in hepatocellular carcinoma. Here, we systematically review the evidence implicating tumor suppressors in the development of hepatocellular carcinoma.

As a result of vascular injury, activated platelets will rapidly interact with circulating platelets, via membrane glycoprotein complex alphaIIbbeta3 (GPIIb-IIIa) and fibrinogen, to form a thrombus or a plug preventing fatal bleeding. In addition, platelets interacting with ruptured atherosclerotic plaques or with the surface of diseased vessels can aggregate and induce ischemia that prevents blood flow. However, increasing evidence has also shown that circulating platelets interact with leukocytes and endothelial cells, via specific adhesion molecules, in inflammation, vascular remodelling and thrombosis. The aim of this chapter is to present the importance of cell-cell interactions involving platelets and leukocytes in events related to inflammation, coagulation, vascular remodelling and thrombosis. A key adhesion molecule implicated in platelet interaction with leukocytes is P-selectin, also known as CD62P. It is present on activated platelets and endothelial cells, and its counterpart on leukocytes is known as P-selectin glycoprotein ligand-1 (PSGL-1). A critical co-factor leading to leukocyte activation in platelet-monocyte aggregate formation is the presence of a chemokine known as RANTES. It acts in concert with platelet P-selectin and PSGL-1 in monocyte stimulation.

The histidine triad (HIT) superfamily comprises proteins that share the histidine triad motif, His-ϕ-His-ϕ-His-ϕ-ϕ, where ϕ is a hydrophobic amino acid. HIT proteins are ubiquitous in prokaryotes and eukaryotes. HIT proteins bind nucleotides and exert dinucleotidyl hydrolase, nucleotidylyl transferase or phosphoramidate hydrolase enzymatic activity. In humans, 5 families of HIT proteins are recognized. The accumulated epidemiological and experimental evidence indicates that two branches of the superfamily, the HINT (Histidine Triad Nucleotide Binding) members and FHIT (Fragile Histidine Triad), have tumor suppressor properties but a conclusive physiological role can still not be assigned to these proteins. Aprataxin forms another discrete branch of the HIT superfamily, is implicated in DNA repair mechanisms and unlike the HINT and FHIT members, a defective protein can be conclusively linked to a disease, ataxia with oculomotor apraxia type 1. The scavenger mRNA decapping enzyme, DcpS, forms a fourth branch of the HIT superfamily. Finally, the GalT enzymes, which exert specific nucleoside monophosphate transferase activity, form a fifth branch that is not implicated in tumorigenesis. The molecular mechanisms by which the HINT and FHIT proteins participate in bioenergetics of cancer are just beginning to be unraveled. Their purported actions as tumor suppressors are highlighted in this review.