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In this editorial, members of the CMC and Vidu Garg discuss how perturbations in nitric oxide (NO) signalling contribute to calcific aortic valve disease (CAVD) pathogenesis. In particular, the role of tetrahydrobiopterin (BH4) in endothelial NO synthase (eNOS) uncoupling is discussed, an important mechanisms likely operative already early in the disease process and thus of potential therapeutic relevance. Check out the commentary recently published in the EHJ.