The pleiotropic effects of antithrombotic drugs in the metabolic-cardiovascular-neurodegenerative disease continuum: impact beyond reduced clotting.

Antithrombotic drugs are widely used for primary and secondary prevention, as well as treatment of many cardiovascular disorders. Over the past few decades, major advances in the pharmacology of these agents have been made with the introduction of new drug classes as novel therapeutic options. Accumulating evidence indicates that the beneficial outcomes of some of these antithrombotic agents are not solely related to their ability to reduce thrombosis.

Challenging inflammatory process at molecular, cellular and in vivo levels via some new pyrazolyl thiazolones.

The work reported herein describes the synthesis of a new series of anti-inflammatory pyrazolyl thiazolones. In addition to COX-2/15-LOX inhibition, these hybrids exerted their anti-inflammatory actions through novel mechanisms. The most active compounds possessed COX-2 inhibitory activities comparable to celecoxib (IC values of 0.

The Emerging Role of COX-2, 15-LOX and PPARγ in Metabolic Diseases and Cancer: An Introduction to Novel Multi-target Directed Ligands (MTDLs).

Emerging evidence supports an intertwining framework for the involvement of different inflammatory pathways in a common pathological background for a number of disorders. Of importance are pathways involving arachidonic acid metabolism by cyclooxygenase-2 (COX-2) and 15-lipoxygenase (15-LOX). Both enzyme activities and their products are implicated in a range of pathophysiological processes encompassing metabolic impairment leading to adipose inflammation and the subsequent vascular and neurological disorders, in addition to various pro- and antitumorigenic effects.

Impaired cross-talk between NO and hyperpolarization in myoendothelial feedback: a novel therapeutic target in early endothelial dysfunction of metabolic disease.

Over the past three decades, our view of the endothelium rapidly evolved from a static lining of the blood vessels to a dynamic determinant and regulator of vascular tone and homeostasis. It is now widely accepted that endothelial dysfunction is a hallmark of almost every vascular pathology, either as a cause or a consequence. The tight association between the metabolic disease spectrum, ranging from mild alterations of blood lipids profile all the way to diabetes and morbid obesity; and vascular complications argues for a deleterious endothelial remodeling in these conditions.