Current Pharmaceutical Design - Volume 15, Issue 27, 2009

Coronary heart disease is the leading cause of morbidity and mortality worldwide. Atherosclerosis is a common denominator underlying most clinical manifestations of cardiovascular disease. It is a complex inflammatory process characterized by the cross-talk between excessive inflammation and lipid accumulation. Despite of extensive research, there are several unmet needs in the management of atherosclero Read More

The accumulation of lipids within arteries remains to be the initial impulse for the pathogenesis of atherosclerosis; however, both inflammation and oxidative stress are considered to play a critical role in this process. Several lipid lowering drugs are used as the first line therapy in atherosclerosis; however, different agents have been found to exhibit beneficial effects which are independent of their lipid lowering activity. Both statins Read More

Atherosclerosis is a complex inflammatory process characterized by the cross-talk between excessive inflammation and lipid accumulation. In the past few years, compelling evidence suggests that statins can decrease vascular inflammation and attenuate the development of atherosclerosis through their so-called “pleiotropic effects”. These cholesterol-independent effects are predominantly due to their ability to inhibit isopre Read More

The inflammatory environment within the atherosclerotic lesion stimulates the 5-lipoxygenase pathway of arachidonic acid metabolism, leading to the biosynthesis of the potent lipid inflammatory mediators leukotrienes. The present review summarizes the components of this pathway; the enzymes 5-lipoxygenase (5-LO, ALOX5) with its activating protein, FLAP (ALOX5AP), LTA4 hydrolase and LTC4 synthase, as well as the rec Read More

Nitric oxide (NO) produced by endothelial NO synthase (eNOS) represents an anti-atherosclerotic principle. NO bioavailability is decreased in atherosclerosis due to increased NO inactivation by reactive oxygen species and reduced NO synthesis. Various types of vascular pathophysiology are associated with oxidative stress, with NADPH oxidases as the major source of reactive oxygen species. These inactivate NO. Also, oxi Read More

The plasma levels of high-density lipoprotein (HDL) cholesterol are inversely correlated with the risk of atherosclerosis and cardiovascular disease (CVD) in humans. One of the major mechanisms whereby HDL particles protect against atherosclerosis is that of reverse cholesterol transport from atherosclerotic lesion macrophages to the liver. HDL particles also exhibit various antiatherogenic and cardioprotective effects by modul Read More

Although treatment with statins significantly reduces adverse cardiovascular outcomes, several studies have shown that cardiovascular events continue to occur in two thirds of all patients. A logical pharmacologic approach to further reduce cardiovascular disease mortality should be focused on direct modifiers of atherosclerosis or lipid-modifying agents with different mechanism of action than existing drugs against d Read More

Type 2 diabetes is associated with substantially increased cardiovascular mortality. The need to reduce the progression of atherosclerosis alongside lowering blood glucose levels is now well established. Ideally, pharmaceutical treatment should address both of these needs. This review summarises current evidence of the anti-atherosclerotic effects exerted by oral antidiabetic agents. Metformin has so far consistently su Read More

The growing knowledge about genetic influence on cardiovascular diseases (CVD) combined with the recently generated amounts of genomic data hold promise to the identification of new markers for atherosclerotic CVD. Cardiovascular pharmacogenomics and pharmacogenetics have now the potential for leading to identification of genetic contributors and therefore to the development of predictive genetic tests that could opti Read More