4-Hydroxynonenal and cholesterol oxidation products in atherosclerosis

4-Hydroxynonenal (HNE) is by far the most investigated aldehydic end-product of oxidative breakdown of membrane n-6 polyunsaturated fatty acids. Its potential involvement in the pathogenesis of atherosclerosis has been corroborated by its consistent detection in both oxidized LDL and fibrotic plaque in humans. HNE has been shown to activate both macrophage and smooth muscle cells, i.e. the two key cell types in chronic inflammatory processes characterized by excessive fibrogenesis. By signalling to the nucleus, the aldehyde may up-regulate in these cells both expression and synthesis of monocyte chemotactic protein 1 (MCP-1) and transforming growth factor beta1 (TGFbeta1). Oxysterols, namely 27 carbon atoms oxidation products of cholesterol, are found in relatively high amount in LDL from hypercholesterolemic individuals and are consistently detectable in foam cells and necrotic core of human atherosclerotic lesion. As for HNE, the challenge of cells of the macrophage lineage with a mixture of oxysterols like that detectable in hypercholesterolemic individuals led to a marked overexpression of TGFbeta1 and MCP-1. Both HNE and oxysterols then appear to be candidates for a primary role in the progression of the atherosclerotic process.     

Influence of lipid peroxidation on lipoprotein secretion by isolated hepatocytes

Isolated rat liver cells have been exposed to 3 different lipid peroxidation-inducing agents, CCl₄, FeCl₃ and cumene hydroperoxide, and the rates of malonaldehyde production and of lipoprotein secretion have been compared. Results indicate that it is possible to induce a high degree of lipid peroxidation without inducing strong changes in lipoprotein secretion. Only in CCl₄-poisoned hepatocytes is lipoprotein secretion strongly impaired. In this experimental condition, the effect of free radical scavengers, or inhibitors of lipid peroxidation, has been studied; the degree of covalent binding of CCl₄ metabolites to hepatocyte proteins, as well as the behavior of both lipid peroxidation and lipoprotein secretion, have been evaluated. Promethazine and propyl gallate prevented malonaldehyde production, but neither agent reduced covalent binding nor improved secretion. Menadione, on the contrary, besides inhibiting malonaldehyde production, decreased covalent binding and protected against the impairment of secretion. These data lead to the conclusion that covalent binding of CCl₄ metabolites, rather than lipid peroxidation products, accounts for the derangement of lipoprotein secretion in CCl₄-poisoned liver cells. Presented in part at the ISF-AOCS World Congress, New York, April 1980.     

Controlling the Cassie-to-Wenzel Transition: an Easy Route towards the Realization of Tridimensional Arrays of Biological Objects

Nano-Micro Letters - In this paper we provide evidence that the Cassie-to-Wenzel transition, despite its detrimental effects on the wetting properties of superhydrophobic surfaces, can be exploited...     

The lipid peroxidation end product 4-hydroxy-2,3-nonenal up-regulates transforming growth factor beta1 expression in the macrophage lineage: a link between oxidative injury and fibrosclerosis

An increasing number of reports underscore the frequent association of fibrosclerotic diseases of lung, liver, arterial wall, brain, etc., with the accumulation of oxidatively modified lipids and proteins. A cause-and-effect relationship has been proposed between cellular oxidative damage and increased fibrogenesis based on the fact that experimental treatment with antioxidants either prevents or quenches the fibrotic process. With some peculiarities in the different organs, fibrosclerosis is essentially the result of the interaction of macrophages and extracellular matrix-producing cells. The cross-talk is mediated by fibrogenic cytokines, among which the most important appears to be transforming growth factor beta1 (TGF-beta1). This report describes treatment of different types of macrophage, of both human and murine origin, with 4-hydroxy-2,3-nonenal (HNE) a major aldehyde end product of membrane lipid oxidation found consistently to induce both mRNA expression and synthesis of TGF-beta1. Since increased HNE levels have been demostrated in the cirrhotic liver and in the oxidatively modified low-density human lipoproteins associated with atherosclerosis, the up-regulation of macrophage TGF-beta1 by HNE appears to be involved in the pathogenesis of these and similar diseases characterized by fibrosclerosis.     

Controlling DNA Bundle Size and Spatial Arrangement in Self-assembled Arrays on Superhydrophobic Surface

Nano-Micro Letters - The use of superhydrophobic surfaces (SHSs) is now emerging as an attractive platform for the realization of one-dimensional (1D) nanostructures with potential applications in...