Molecular mechanisms underlying the onset of degenerative aortic valve disease

Daihiko Hakuno, Naritaka Kimura, Masatoyo Yoshioka, Keiichi Fukuda

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Morbidity from degenerative aortic valve disease is increasing worldwide, concomitant with the ageing of the general population and the habitual consumption of diets high in calories and cholesterol. Immunohistologic studies have suggested that the molecular mechanism occurring in the degenerate aortic valve resembles that of atherosclerosis, prompting the testing of HMG CoA reductase inhibitors (statins) for the prevention of progression of native and bioprosthetic aortic valve degeneration. However, the effects of these therapies remain controversial. Although the molecular mechanisms underlying the onset of aortic valve degeneration are largely unknown, research in this area is advancing rapidly. The signaling components involved in embryonic valvulogenesis, such as Wnt, TGF-β1, BMP, and Notch, are also involved in the onset of aortic valve degeneration. Furthermore, investigations into extracellular matrix remodeling, angiogenesis, and osteogenesis in the aortic valve have been reported. Having noted avascularity of normal cardiac valves, we recently identified chondromodulin-I (chm-I) as a crucial anti-angiogenic factor. The expression of chm-I is restricted to cardiac valves from late embryogenesis to adulthood in the mouse, rat, and human. In human degenerate atherosclerotic valves, the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases and angiogenesis is observed in the area of chm-I downregulation. Gene targeting of chm-I resulted in VEGF expression, angiogenesis, and calcification in the aortic valves of aged mice, and aortic stenosis is detected by echocardiography, indicating that chm-I is a crucial factor for maintaining normal cardiac valvular function by preventing angiogenesis. The present review focuses on the animal models of aortic valve degeneration and recent studies on the molecular mechanisms underlying the onset of degenerative aortic valve disease.

Original languageEnglish
Pages (from-to)17-24
Number of pages8
JournalJournal of Molecular Medicine
Volume87
Issue number1
DOIs
Publication statusPublished - 2009 Jan

Fingerprint

Aortic Diseases
Aortic Valve
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Heart Valves
Vascular Endothelial Growth Factor A
Gene Targeting
Angiogenesis Inducing Agents
Aortic Valve Stenosis
Matrix Metalloproteinases
Osteogenesis
Embryonic Development
Extracellular Matrix
Echocardiography
Atherosclerosis
Down-Regulation
Animal Models
Cholesterol
Diet
Morbidity

Keywords

  • Angiogenesis
  • Calcification
  • Cardiovascular
  • MMP
  • VEGF

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

Cite this

Molecular mechanisms underlying the onset of degenerative aortic valve disease. / Hakuno, Daihiko; Kimura, Naritaka; Yoshioka, Masatoyo; Fukuda, Keiichi.

In: Journal of Molecular Medicine, Vol. 87, No. 1, 01.2009, p. 17-24.

Research output: Contribution to journalArticle

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