Fine Tuning Therapeutic Targeting of the Sphingolipid Biosynthetic Pathway to Treat Atherosclerosis

Authors: Kim, W. S.; Chalfant, Charles E.; Garner, Brett

Source: Current Vascular Pharmacology, Volume 4, Number 2, April 2006 , pp. 151-154(4)

Publisher: Bentham Science Publishers

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Abstract:

The accumulation of sphingolipids, including sphingomyelin and glycosphingolipids, in atherosclerotic lesions is well known. Plasma sphingomyelin concentration is correlated with atherosclerosis development and is an independent predictor of coronary artery disease. Similarly, plasma glycosphingolipid levels are increased in conditions associated with atherosclerosis risk. Recent studies have focused on understanding the mechanisms by which specific intermediates and end-products of the sphingolipid biosynthetic pathway, such as sphingomyelin, glycosphingolipids, ceramide and sphingosine-1-phosphate may modulate vascular biology and atherosclerosis. Here we focus on recent work indicating that pharmacological modulation of the sphingolipid biosynthetic pathway could offer a novel treatment for atherosclerosis or, at the very least, provide mechanistic insights concerning the eitiology of this disease which is the major cause of death in developed countries.

Keywords: Atherosclerosis; sphingomyelin; glycosphingolipids; ceramide kinase; ceramide-1-phosphate; myriocin; sphingolipid; inhibitors; ABCA-1

Document Type: Research article

DOI: http://dx.doi.org/10.2174/157016106776359844

Affiliations: 1: Prince of Wales Medical Research Institute, Randwick, NSW 2031, Australia.

Publication date: 2006-04-01

More about this publication?

Vascular disease is the commonest cause of death in Westernized countries and its incidence is on the increase in developing countries. It follows that considerable research is directed at establishing effective treatment for acute vascular events. Long-term treatment has also received considerable attention (e.g. for symptomatic relief). Furthermore, effective prevention, whether primary or secondary, is backed by the findings of several landmark trials.

Vascular disease is a complex field with primary care physicians and nurse practitioners as well as several specialties involved. The latter include cardiology, vascular and cardio thoracic surgery, general medicine, radiology, clinical pharmacology and neurology (stroke units). Current Vascular Pharmacology will publish reviews to update all those concerned with the treatment of vascular disease. For example, reviews commenting on recently published trials or new drugs will be included. In addition to clinically relevant topics we will consider 'research-based' reviews dealing with future developments and potential drug targets. Therefore, another function of Current Vascular Pharmacology is to bridge the gap between clinical practice and ongoing research.

Debates will also be encouraged in the correspondence section of this journal.

Fine Tuning Therapeutic Targeting of the Sphingolipid Biosynthetic Pathway to Treat Atherosclerosis

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