Am J Cardiovasc Dis 2011;1(2):185-199
Review Article
Pathogenesis of aortic stenosis: not just a matter of wear and tear
Aaron L Sverdlov, Doan TM Ngo, Matthew J Chapman, Onn Akbar Ali, Yuliy Y Chirkov, John D Horowitz
The Queen Elizabeth Hospital, University of Adelaide, South Australia, Australia
Received July 3, 2011; accepted July 20, 2011; Epub July 28, 2011; published August 15, 2011
Abstract: Aortic valve stenosis (AS) is the commonest form of valvular heart disease in the Western world. Its prevalence
increases exponentially with age and it is present in 2-7% of all patients over 65 years of age. In view of the considerable
cardiovascular morbidity and mortality associated not only with AS, but even its earlier stage, aortic sclerosis, many
investigations have been directed towards better understanding of its pathogenesis, with the ultimate objective of
developing strategies to retard its progression. Although risk factors and downstream mediators appear similar for AS and
atherosclerosis (older age, male sex, hypertension, smoking, hypercholesterolemia, and diabetes, as many as 50% of
patients with AS do not have clinically significant atherosclerosis. On the basis both of recent experimental evidence and
clinical trials, it appears that atherogenesis is not pivotal to the pathogenesis of AS. On the other hand, there is increasing
evidence of active involvement of aortic valve fibroblasts with resultant increased production of reactive oxygen species,
active pro-inflammatory and pro-fibrotic processes culminating in calcification. We also discuss the evidence of
involvement of the nitric oxide system in the pathogenesis of AS. The renin-angiotensin system has also emerged as a
major player in the pathogenesis of AS. Histologically, there is increased ACE expression and elevated angiotensin II
levels in stenotic valves, while we have just demonstrated amelioration of AS with the use of ACE inhibitors in an animal
model. We further discuss intervention studies aimed at retarding AS progression, including recent failures of statins to
retard progression of AS in large randomized clinical studies. Finally, we discuss the special case of bicuspid aortic valve,
including its genetics and unique associated features. (AJCD1107002).
Keywords: Aortic valve stenosis, bicuspid aortic valve, nitric oxide, oxidative stress, inflammation, fibrosis, calcification,
intervention studies
Full Text PDF
Address all correspondence to:
John D Horowitz, MD
Cardiology Unit, The Queen Elizabeth Hospital, University of Adelaide,
28 Woodville Road, Woodville, SA 5011, Australia.
Tel.: +61 8 82226000; fax: +61 8 82227201.
E-mail address: john.horowitz@adelaide.edu.au
Review Article
Pathogenesis of aortic stenosis: not just a matter of wear and tear
Aaron L Sverdlov, Doan TM Ngo, Matthew J Chapman, Onn Akbar Ali, Yuliy Y Chirkov, John D Horowitz
The Queen Elizabeth Hospital, University of Adelaide, South Australia, Australia
Received July 3, 2011; accepted July 20, 2011; Epub July 28, 2011; published August 15, 2011
Abstract: Aortic valve stenosis (AS) is the commonest form of valvular heart disease in the Western world. Its prevalence
increases exponentially with age and it is present in 2-7% of all patients over 65 years of age. In view of the considerable
cardiovascular morbidity and mortality associated not only with AS, but even its earlier stage, aortic sclerosis, many
investigations have been directed towards better understanding of its pathogenesis, with the ultimate objective of
developing strategies to retard its progression. Although risk factors and downstream mediators appear similar for AS and
atherosclerosis (older age, male sex, hypertension, smoking, hypercholesterolemia, and diabetes, as many as 50% of
patients with AS do not have clinically significant atherosclerosis. On the basis both of recent experimental evidence and
clinical trials, it appears that atherogenesis is not pivotal to the pathogenesis of AS. On the other hand, there is increasing
evidence of active involvement of aortic valve fibroblasts with resultant increased production of reactive oxygen species,
active pro-inflammatory and pro-fibrotic processes culminating in calcification. We also discuss the evidence of
involvement of the nitric oxide system in the pathogenesis of AS. The renin-angiotensin system has also emerged as a
major player in the pathogenesis of AS. Histologically, there is increased ACE expression and elevated angiotensin II
levels in stenotic valves, while we have just demonstrated amelioration of AS with the use of ACE inhibitors in an animal
model. We further discuss intervention studies aimed at retarding AS progression, including recent failures of statins to
retard progression of AS in large randomized clinical studies. Finally, we discuss the special case of bicuspid aortic valve,
including its genetics and unique associated features. (AJCD1107002).
Keywords: Aortic valve stenosis, bicuspid aortic valve, nitric oxide, oxidative stress, inflammation, fibrosis, calcification,
intervention studies
Full Text PDF
Address all correspondence to:
John D Horowitz, MD
Cardiology Unit, The Queen Elizabeth Hospital, University of Adelaide,
28 Woodville Road, Woodville, SA 5011, Australia.
Tel.: +61 8 82226000; fax: +61 8 82227201.
E-mail address: john.horowitz@adelaide.edu.au
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