Multi-parametric thrombus profiling microfluidics detects intensified biomechanical thrombogenesis associated with hypertension and aging

Misbahud Din, Souvik Paul, Sana Ullah, Haoyi Yang, Rong-Guang Xu, Nurul Aisha Zainal Abidin, Allan Sun, Yiyao Catherine Chen, Rui Gao, Bari Chowdhury, Fangyuan Zhou, Stephenie Rogers, Mariel Miller, Atreyee Biswas, Liang Hu, Zhichao Fan, Christopher Zahner, Jing Fan, Zi Chen, Megan Berman, Lingzhou Xue, Lining Arnold Ju and Yunfeng Chen ()
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Misbahud Din: The University of Texas Medical Branch
Souvik Paul: The University of Texas Medical Branch
Sana Ullah: The University of Texas Medical Branch
Haoyi Yang: University Park
Rong-Guang Xu: The University of Texas Medical Branch
Nurul Aisha Zainal Abidin: The University of Sydney
Allan Sun: The University of Sydney
Yiyao Catherine Chen: The University of Sydney
Rui Gao: The University of Sydney
Bari Chowdhury: The University of Texas Medical Branch
Fangyuan Zhou: Georgia Institute of Technology
Stephenie Rogers: The University of Texas Medical Branch
Mariel Miller: The University of Texas Medical Branch
Atreyee Biswas: The University of Texas Medical Branch
Liang Hu: Shanghai University of Traditional Chinese Medicine
Zhichao Fan: UConn Health
Christopher Zahner: The University of Texas Medical Branch
Jing Fan: The City University of New York - City College
Zi Chen: Harvard Medical School
Megan Berman: The University of Texas Medical Branch
Lingzhou Xue: University Park
Lining Arnold Ju: The University of Sydney
Yunfeng Chen: The University of Texas Medical Branch

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Arterial thrombosis is a leading cause of death and disability worldwide with no effective bioassay for clinical prediction. As a symbolic feature of arterial thrombosis, severe stenosis in the blood vessel creates a high-shear, high-gradient flow environment that facilitates platelet aggregation towards vessel occlusion. Here, we present a thrombus profiling assay that monitors the multi-dimensional attributes of thrombi forming in such biomechanical conditions. Using this assay, we demonstrate that different receptor–ligand interactions contribute distinctively to the composition and activation status of the thrombus. Our investigation into hypertensive and older individuals reveals intensified biomechanical thrombogenesis and multi-dimensional thrombus profile abnormalities, endorsing the diagnostic potential of the assay. Furthermore, we identify the hyperactivity of GPIbα-integrin αIIbβ3 mechanosensing axis as a molecular mechanism that contributes to hypertension-associated arterial thrombosis. By studying drug-disease interactions and inter-individual variability, our work reveals a need for personalized anti-thrombotic drug selection that accommodates each patient’s pathological profile.

Date: 2024
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DOI: 10.1038/s41467-024-53069-9

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