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Updated: Jan 1, 2026

In Vitro Model Integrating Substrate Stiffness and Flow to Study Endothelial Cell Responses
Published on: July 19, 2024
The interplay of signaling pathway in endothelial cells-matrix stiffness dependency with targeted-therapeutic drugs
Vicki Vania1, Lu Wang1, Marco Tjakra1
1Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China.
Insights
Matrix stiffness significantly influences cardiovascular diseases (CVDs) by affecting endothelial cells. Understanding these mechanobiology pathways, like RhoA/ROCK and MAPK, is crucial for developing new CVD therapies.
Area of Science:
- Mechanobiology
- Cardiovascular Research
- Cellular Pathophysiology
Background:
- Cardiovascular diseases (CVDs) are a leading cause of global mortality.
- Cell chemotaxis has been a long-standing focus in CVD research.
- Mechanical stimuli increasingly recognized for their role in arterial pathophysiology and endothelial dysfunction, key to atherosclerosis.
Purpose of the Study:
- To review how matrix stiffness mediates atherogenesis in endothelial cells.
- To explore signaling pathways (RhoA/ROCK, MAPK, Hippo) and mechanosensitive non-coding RNAs involved.
- To discuss tunable hydrogels for advancing CVD research.
Main Methods:
- Literature review focusing on mechanobiology and CVD.
- Analysis of signaling pathways influenced by matrix stiffness.
- Examination of non-coding RNAs in matrix stiffness-mediated atherogenesis.
Main Results:
- Matrix stiffness impacts endothelial cells through RhoA/ROCK, MAPK, and Hippo pathways.
- Mechanosensitive non-coding RNAs play a role in matrix stiffness-driven atherogenesis.
- Tunable hydrogels offer potential for future research strategies.
Conclusions:
- Matrix stiffness is a critical factor in cardiovascular disease development.
- Targeting mechanobiology pathways presents therapeutic opportunities for CVDs.
- Further research using advanced materials like tunable hydrogels is needed.
Abstract:
Cardiovascular diseases (CVDs) have been one of the major causes of human deaths in the world. The study of CVDs has focused on cell chemotaxis for decades. With the advances in mechanobiology, accumulating evidence has demonstrated the influence of mechanical stimuli on arterial pathophysiology and endothelial dysfunction that is a hallmark of atherosclerosis development. An increasing number of drugs have been exploited to decrease the stiffness of vascular tissue for CVDs therapy. However, the underlying mechanisms have yet to be explored. This review aims to summarize how matrix stiffness mediates atherogenesis through various important signaling pathways in endothelial cells and cellular mechanophenotype, including RhoA/Rho-associated protein kinase (ROCK), mitogen-activated protein kinase (MAPK), and Hippo pathways. We also highlight the roles of putative mechanosensitive non-coding RNAs in matrix stiffness-mediated atherogenesis. Finally, we describe the usage of tunable hydrogel and its future strategy to improve our knowledge underlying matrix stiffness-mediated CVDs mechanism.
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