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

Kumar Subramani; Jeffrey Bander; Sixia Chen; Mayte Suárez-Fariñas; Thamizhiniyan Venkatesan; Sandeep Subrahmanian; Rohan Varshney; Annapoorna Kini; Samin Sharma; Daniel B Rifkin; Jaehyung Cho; Barry S Coller; Jasimuddin Ahamed

doi:10.1016/j.jacbts.2023.09.007

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

JACC Basic Transl Sci. 2023 Nov 1;9(2):185-199. doi: 10.1016/j.jacbts.2023.09.007. eCollection 2024 Feb.

Affiliations

¹ Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
² Icahn School of Medicine at Mount Sinai New York, New York, USA.
³ University of Oklahoma Health Sciences Centers, Oklahoma City, Oklahoma, USA.
⁴ Departments of Cell Biology and Medicine, New York University, New York, New York, USA.
⁵ Washington University School of Medicine, St. Louis, Missouri, USA.
⁶ Laboratory of Blood and Vascular Biology, Rockefeller University, New York, New York, USA.

Abstract

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.

Keywords: AVWS; GI bleeding; Heyde’s syndrome; TGF-beta; anemia; aortic stenosis.