Prof. Gaetano Thiene,
• The biology and natural history of calcific aortic stenosis.• Sortilin 1 and Caveolin 1 play a major role in initiating dystrophic calcification.• Leukotriene eases disease progression & may be helpful in preventing calsific aortic stenosis.• Therapy targets discussed.
The first speaker, C.M. Otto (Seattle, US) focused on risk factors: age, males LDL, Lp(a), hypertension, smoking, metabolic syndrome. SNP was found in Lp(a) locus in patients with calcific aortic valve stenosis. Natural course consists of valve sclerosis, evidence of early atherosclerosis and eventually dystrophic calcification. Calcification is accelerated in Bicuspid Aortic Valve, where a pathogenic mutation was found in Notch gene.
E. Aikawa (Boston, US) spoke about cell biology, showing that early calcification occurs upon extracellular matrix vesicles, which are full of phosphorus and combine with Ca++ and calcium phosphate deposits. Sortilin 1 and Caveolin 1 play a major role in initiating dystrophic calcification, with a mechanism similar to that which occurs in bone formation.
M. Back (Stockholm, SE) drew the attention to mechanical factors like pressure, turbulent flow, microfractures with haemorrhage, shear stress. Leukotriene was proven to play a role in disease progression. Leukotriene receptor antagonists may be used for possible prevention.
D.E. Newby from (Edinburgh, Scotland) came across possible therapy targets: a) lipid deposition with statin treatment; b) inflammation with interleukin 1 receptor antagonists; c) calcification with bisphosphonates; d) mechanical injury with blood pressure control; e) myocardial fibrosis with angiotensin inhibitors.
Discussion, at the end of each presentation, was quite lively. The problem whether calcific aortic valve should be considered a phenotype of atherosclerosis was raised as well as the relationship with osteoporosis. The role of hypertension in the onset and progression of calcific aortic valve disease remains controversial. The four speakers were outstanding and the symposium exceeded all the expectations.
Calcific aortic stenosis: where will basic science lead us?, Science in Practice on aortic valve disease
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