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CARDIOVASCULAR GENOMIC MEDICINE

Genomics

The Next Step to Elucidate the Etiology of Calcific Aortic Valve Stenosis

Yohan Bossé, PhD^_*,,_*, Patrick Mathieu, MD and Philippe Pibarot, DVM, PhD, FACC, FAHA

^_* Department of Anatomy and Physiology, Laval Hospital Research Center, Laval University, Quebec City, Quebec, Canada
Laval University Hospital Research Center (CRCHUL), Quebec City, Quebec, Canada
Department of Surgery, Laval Hospital Research Center/Quebec Heart Institute, Laval University, Quebec City, Quebec, Canada
Department of Medicine, Research Group in Valvular Heart Diseases, Laval Hospital Research Center/Quebec Heart Institute, Laval University, Quebec City, Quebec, Canada.

Manuscript received October 23, 2007; revised manuscript received November 27, 2007, accepted December 10, 2007.

^_* Reprint requests and correspondence: Dr. Yohan Bossé, Laval Hospital Research Centre, Pavillon Margeritte-d’Youville, Y4190, 2725, Chemin Sainte-Foy, Québec City, Québec, Canada G1V 4G5. (Email: yohan.bosse{at}crhl.ulaval.ca).

With the current shift toward an older population, calcific aortic valve stenosis (AVS) is likely to become a major societal and economic burden. For many years, AVS was regarded as a degenerative and nonmodifiable process. However, molecular studies unanimously demonstrated that AVS is an actively regulated disorder with several potential therapeutic targets. Many factors are predicted to cause AVS, and an important genetic predisposition is anticipated. In this review, we describe candidate genes and signaling pathways identified by genetic research and incorporate this new knowledge into a more comprehensive picture of factors involved in the pathogenesis of AVS. We also emphasize the need for additional studies to elucidate its complete genetic architecture. Recent advances in genomic research offer a remarkable opportunity to investigate AVS at the most fundamental level. The benefits of these new approaches can be observed in many complex diseases, but the field of AVS is trailing behind. We discuss the future utility of these new genomic approaches to improve our understanding of AVS and to refine the management of patients in terms of diagnosis, prevention, and treatment.

Abbreviations and Acronyms   AVS = aortic valve stenosis   IL = interleukin   SNP = single nucleotide polymorphism   TGF = transforming growth factor

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