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

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

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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.

Original language	English
Pages (from-to)	185-199
Number of pages	15
Journal	JACC: Basic to Translational Science
Volume	9
Issue number	2
DOIs	https://doi.org/10.1016/j.jacbts.2023.09.007
State	Published - Feb 2024

Keywords

AVWS
GI bleeding
Heyde's syndrome
TGF-beta
anemia
aortic stenosis

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10.1016/j.jacbts.2023.09.007

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Subramani, K., Bander, J., Chen, S., Suárez-Fariñas, M., Venkatesan, T., Subrahmanian, S., Varshney, R., Kini, A., Sharma, S., Rifkin, D. B., Cho, J., Coller, B. S., & Ahamed, J. (2024). Evidence That Anemia Accelerates AS Progression Via Shear-Induced TGF-β1 Activation: Heyde's Syndrome Comes Full Circle. JACC: Basic to Translational Science, 9(2), 185-199. https://doi.org/10.1016/j.jacbts.2023.09.007

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

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",

author = "Kumar Subramani and Jeffrey Bander and Sixia Chen and Mayte Su{\'a}rez-Fari{\~n}as and Thamizhiniyan Venkatesan and Sandeep Subrahmanian and Rohan Varshney and Annapoorna Kini and Samin Sharma and Rifkin, {Daniel B.} and Jaehyung Cho and Coller, {Barry S.} and Jasimuddin Ahamed",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

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doi = "10.1016/j.jacbts.2023.09.007",

language = "English",

volume = "9",

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Subramani, K, Bander, J, Chen, S, Suárez-Fariñas, M, Venkatesan, T, Subrahmanian, S, Varshney, R, Kini, A, Sharma, S, Rifkin, DB, Cho, J, Coller, BS & Ahamed, J 2024, 'Evidence That Anemia Accelerates AS Progression Via Shear-Induced TGF-β1 Activation: Heyde's Syndrome Comes Full Circle', JACC: Basic to Translational Science, vol. 9, no. 2, pp. 185-199. https://doi.org/10.1016/j.jacbts.2023.09.007

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T1 - Evidence That Anemia Accelerates AS Progression Via Shear-Induced TGF-β1 Activation

T2 - Heyde's Syndrome Comes Full Circle

AU - Subramani, Kumar

AU - Bander, Jeffrey

AU - Chen, Sixia

AU - Suárez-Fariñas, Mayte

AU - Venkatesan, Thamizhiniyan

AU - Subrahmanian, Sandeep

AU - Varshney, Rohan

AU - Kini, Annapoorna

AU - Sharma, Samin

AU - Rifkin, Daniel B.

AU - Cho, Jaehyung

AU - Coller, Barry S.

AU - Ahamed, Jasimuddin

PY - 2024/2

Y1 - 2024/2

N2 - 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.

AB - 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.

KW - AVWS

KW - GI bleeding

KW - Heyde's syndrome

KW - TGF-beta

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SN - 2452-302X

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JF - JACC: Basic to Translational Science

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ER -

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

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