This study provides the first evidence that epigenetic modifications, specifically decreased DNA-methylation of the 5-LO promoter, play a role in the phenotypic plasticity of valvular interstitial cells in aortic valve stenosis.
No immediate clinical implications for aortic stenosis; hypothesis-generating for 5-LO epigenetic targeting in valvular disease.
Valvular interstitial cells (VICs) are of mesenchymal origin and may differentiate into immune-like cells. This phenotypic plasticity is a key feature of aortic valve stenosis, but the role of epigenetic mechanisms has not previously been explored. Here we compared normal and calcified human aortic valve tissue. Calcified tissue exhibited decreased DNA-methylation in the promoter of the gene encoding the proinflammatory enzyme 5-lipoxygenase (5-LO), accompanied by increased 5-LO mRNA levels. Treatment of cultured VICs with the DNA methyltransferase inhibitor: 5-Aza-2'-deoxycytidine increased 5-LO mRNA levels and leukotriene production. These findings provide a first piece of evidence for epigenetic modifications of VICs in valvular heart disease.
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Nagy et al. (2012) studied this question.
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