**Author details**

Ioan Tilea1 , Horatiu Suciu3 , Brindusa Tilea2 , Cristina Maria Tatar1 , Mihaela Ispas3 and Razvan Constantin Serban3

1 Internal Medicine Clinic, Division of Cardiology, University of Medicine and Pharmacy Tirgu Mures, Romania

2 Infectious Disease Clinic, University of Medicine and Pharmacy Tirgu Mures, Romania

3 Cardiology Clinic, Emergency Clinical County Hospital Tirgu Mures, Romania

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54 Calcific Aortic Valve Disease

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**Section 2**

**Mechanisms of Calcific Aortic Valve Disease**

**Mechanisms of Calcific Aortic Valve Disease**

**Chapter 3**

**Developmental Pathways in CAVD**

Elaine E. Wirrig and Katherine E. Yutzey

http://dx.doi.org/10.5772/54356

**1. Introduction**

Additional information is available at the end of the chapter

link between valve development and disease mechanisms [4].

arative functions or contribute to the progression of CAVD.

Calcific Aortic Valve Disease (CAVD) occurs in >2% of the population over 65 years of age and often leads to valvular stenosis that necessitates valve replacement [1]. CAVD is a pro‐ gressive disease, often manifesting first as aortic valve sclerosis and later developing into stenosis and valve dysfunction [2]. The specific molecular and cellular mechanisms of CAVD initiation and advancement are not well defined, and inhibitors of CAVD progres‐ sion have not been identified. The current standard of treatment for CAVD is aortic valve replacement [3]. Presently, there are no pharmacologic-based treatments for CAVD, and new therapeutic approaches for CAVD are needed. The majority of aortic valves that are re‐ placed have congenital malformations, such as bicuspid aortic valve (BAV), establishing a

The molecular mechanisms of CAVD include activation of signaling pathways implicated in both heart valve development (valvulogenesis) and bone development (osteogenesis) [5-8]. These include activation of regulators of progenitor specification, cell proliferation, and dif‐ ferentiation. Heart valves and bone are complex connective tissues with compartmentalized ECM produced by specialized cell types. Over the past several years, extensive progress has been made in defining molecular regulatory mechanisms in heart valve and bone develop‐ ment (Reviewed in [8-10]). Strikingly, regulatory pathways that control development of car‐ tilage, tendon and bone also are active in developing valves [8, 11]. In addition, recent studies have reported induction of molecular regulators of valvulogenesis and osteogenesis in CAVD [7, 12-14]. However, it is not known if these developmental mechanisms have rep‐

Here we review molecular mechanisms of valve and bone development as they relate to mo‐ lecular mechanisms of CAVD. Recent studies have provided evidence for the involvement of specific regulatory pathways in CAVD as activators or inhibitors of disease progression.

and reproduction in any medium, provided the original work is properly cited.

© 2013 Wirrig and Yutzey; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

**Chapter 3**
