# miRNA-regulation at focal adhesions establishes vascular mechanohomeostasis

> **NIH NIH R21** · YALE UNIVERSITY · 2022 · $250,224

## Abstract

PROJECT SUMMARY
 Endothelial cells are exceptional sentinels of tissues' mechanical properties. Endothelial cells sense the
extracellular matrix of the vascular wall via integrin-based adhesions (focal adhesions), and homotypic
adhesion between neighboring tissue cells to regulate changes in matrix composition, turnover and stiffening.
Furthermore, endothelial cells sense and adjust to blood flow hemodynamics through dynamic processes
involving changes in actomyosin and other cytoskeletal stresses, remodeling of focal adhesions and cell
adhesions, and cytoskeleton reorganization. How endothelial cells can buffer changes in forces associated
with both blood flow and extracellular matrix remains unclear. Here, we will study how endothelial cells regulate
matrix and blood flow forces at focal adhesion, and how these mechanism(s) sustain vascular mechanical
homeostasis.
 Cell homeostasis hinges on the activity of microRNAs (miRNAs) through a mechanism that is resilient
and regulates gene expression rapidly. We recently discovered a miRNA network activated by changes in
matrix stiffness. These miRNAs preferentially target cytoskeletal, adhesion and matrix (CAM) genes for post-
transcriptional regulation of protein levels both in vitro and in vivo. We concluded that miRNA-dependent
regulation of CAM genes is critical for mediating cell-matrix interactions and allows endothelial cells to maintain
mechanical homeostasis under conditions of changing stiffness.
 Preliminary data presented in this application shows the novel and exciting observation that miRNAs
and CAM mRNAs are uniquely localized at focal adhesions in endothelial cells. We hypothesize that CAM
mRNAs are localized to and translated at focal adhesions, and that miRNAs post-transcriptionally
regulate CAM protein levels at focal adhesions to buffer the effect of matrix and/or hemodynamic
changes and maintain mechanical homeostasis. We will test this new hypothesis by setting up 2D cell
culture models and the zebrafish vascular system to characterize matrix and/or hemodynamic properties of
endothelial cells that lack of miRNA regulation at focal adhesions.

## Key facts

- **NIH application ID:** 10510869
- **Project number:** 1R21HL165342-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Stefania Nicoli
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $250,224
- **Award type:** 1
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10510869

## Citation

> US National Institutes of Health, RePORTER application 10510869, miRNA-regulation at focal adhesions establishes vascular mechanohomeostasis (1R21HL165342-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10510869. Licensed CC0.

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