Evidence That Anemia Accelerates AS Progression Via Shear-Induced TGF-β1 Activation: Heyde's Syndrome Comes Full Circle.

The severity of aortic stenosis (AS) is associated with acquired von Willebrand syndrome (AVWS) and gastrointestinal bleeding, leading to anemia (Heyde's syndrome). We investigated how anemia is linked with AS and AVWS using the LA100 mouse model and patients with AS. Induction of anemia in LA100 mice increased transforming growth factor (TGF)-β1 activation, AVWS, and AS progression. Patients age >75 years with severe AS had higher plasma TGF-β1 levels and more severe anemia than AS patients age <75 years, and there was a correlation between TGF-β1 and anemia. These data are compatible with the hypothesis that the blood loss anemia of Heyde's syndrome contributes to AS progression via WSS-induced activation of platelet TGF-β1 and additional gastrointestinal bleeding via WSS-induced AVWS.
Competing Interests: This work was supported by grant HL148123 (to Dr Ahamed), in part by HL167656 (to Dr Ahamed), HL19278 (to Dr Coller), a Clinical and Translational Science Award (TR000043) from the National Center for Research Resources and the National Center for Advancing Translational Sciences (NCATS), and National Institutes of Health; and by funds from the Oklahoma Center for Adult Stem Cell Research, Presbyterian Health Foundation, Centers of Biomedical Research Excellence, and Stony Brook University. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(© 2024 The Authors.)