Authors: Rusanescu, Gabriel; Weissleder, Ralph; Aikawa, Elena

Source: Current Cardiology Reviews, Volume 4, Number 3, August 2008 , pp. 148-156(9)

Publisher: Bentham Science Publishers

Abstract:

Recent increase in human lifespan has shifted the spectrum of aging-related disorders to an unprecedented upsurge in cardiovascular diseases, especially calcific aortic valve stenosis, which has an 80% risk of progression to heart failure and death. A current therapeutic option for calcified valves is surgical replacement, which provides only temporary relief. Recent progress in cardiovascular research has suggested that arterial and valve calcification are the result of an active process of osteogenic differentiation, induced by a pro-atherogenic inflammatory response. At molecular level, the calcification process is regulated by a network of signaling pathways, including Notch, Wnt and TGFbeta/BMP pathways, which control the master regulator of osteogenesis Cbfa1/Runx2. Genetic and in vitro studies have implicated Notch signaling in the regulation of macrophage activation and cardiovascular calcification. Individuals with inactivating Notch1 mutations have a high rate of cardiovascular disorders, including valve stenosis and calcification. This article reviews recent progress in the mechanism of cardiovascular calcification and discusses potential molecular mechanisms involved, focusing on Notch receptors. We propose a calcification model where extreme increases in vascular wall cell density due to inflammation-induced cell proliferation can trigger an osteogenic differentiation program mediated by Notch receptors.

Keywords: Calcification; cardiac valve; inflammation; Notch signaling; mesenchymal stem cells; atherosclerosis

Document Type: Research article

Publication date: 2008-08-01

More about this publication?

• Current Cardiology Reviews publishes frontier reviews on all the latest advances on the practical and clinical approach to the diagnosis and treatment of cardiovascular disease. All relevant areas are covered by the journal including arrhythmia, congestive heart failure, cardiomyopathy, congenital heart disease, drugs, methodology, pacing, and preventive cardiology. The journal's aim is to publish the highest quality review articles dedicated to clinical research in the field. The journal is essential reading for all researchers and clinicians in cardiology.

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