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The extracellular matrix mechanics in the vasculature

Nature Cardiovascular Research volume 2, pages 718–732 (2023)Cite this article

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Abstract

Mechanical stimuli from the extracellular matrix (ECM) modulate vascular differentiation, morphogenesis and dysfunction of the vasculature. With innovation in measurements, we can better characterize vascular microenvironment mechanics in health and disease. Recent advances in material sciences and stem cell biology enable us to accurately recapitulate the complex and dynamic ECM mechanical microenvironment for in vitro studies. These biomimetic approaches help us understand the signaling pathways in disease pathologies, identify therapeutic targets, build tissue replacement and activate tissue regeneration. This Review analyzes how ECM mechanics regulate vascular homeostasis and dysfunction. We highlight approaches to examine ECM mechanics at tissue and cellular levels, focusing on how mechanical interactions between cells and the ECM regulate vascular phenotype, especially under certain pathological conditions. Finally, we explore the development of biomaterials to emulate, measure and alter the physical microenvironment of pathological ECM to understand cell–ECM mechanical interactions toward the development of therapeutics.

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Fig. 1: Mechanotransduction in vascular cells.
Fig. 2: Overview of the overlapping pathologic changes in vascular cells and their ECM.
Fig. 3: Selected approaches to measure cell–ECM mechanical interactions.
Fig. 4: Modeling vascular ECM in both large vessels and the microvasculature.

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Acknowledgements

T.B. is a Ford Foundation Predoctoral Fellow. Several studies described from the Gerecht laboratory were funded by a grant from the Air Force Office of Scientific Research (FA9550-20-1-0356 to S.G.).

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  1. These authors contributed equally: Dafu Wang, Travis Brady.

Authors and Affiliations

  1. Department of Biomedical Engineering, Duke University, Durham, NC, USA

    Dafu Wang & Sharon Gerecht

  2. Department of Anesthesiology and Critical Care Medicine and Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Travis Brady & Lakshmi Santhanam

  3. Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA

    Lakshmi Santhanam

  4. Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA

    Lakshmi Santhanam

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D.W. and S.G. prepared the manuscript outline. D.W. and T.B. drafted the tables and figures. D.W., T.B., L.S. and S.G. wrote and edited the manuscript.

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Wang, D., Brady, T., Santhanam, L. et al. The extracellular matrix mechanics in the vasculature. Nat Cardiovasc Res 2, 718–732 (2023). https://doi.org/10.1038/s44161-023-00311-0

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