Abstract: SA-PO975
Extracellular Matrix Stiffness Mediates Human Aortic Smooth Muscle Cell Phenotype via Rho-Kinase
Session Information
- Hypertension and CVD: Mechanisms - II
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Liu, I-Chia, University of Florida, Gainesville, Florida, United States
- Li, Shiyu, University of Florida, Gainesville, Florida, United States
- To, Brandon, University of Florida, Gainesville, Florida, United States
- Mohandas, Rajesh, University of Florida, Gainesville, Florida, United States
Background
Chronic Kidney Disease (CKD) is associated with increased vascular stiffness and accelerated atherosclerosis. However, the mechanisms by which stiffness accelerates the development of atherosclerosis is not known. Rho-kinase (ROCK), a key mechanosensor, influences the phenotype of vascular smooth muscle cells. A synthetic phenotype characterized by increased migration and proliferation of vascular smooth muscle cells is associated with atherosclerosis. We hypothesized that matrix stiffness upregulates ROCK activity to affect vascular smooth muscle cell phenotype.
Methods
Human aortic smooth cells (HASMC) were plated on regular tissue culture plates or polyacrylamide gels engineered to varying stiffness (2kPa – 50kPa). Proliferation of cells was measured by a formazan-based assay. ROCK activity was measured using an ELISA based detection of substrate phosphorylation, and ROCK transcription was assayed by PCR.
Results
Proliferation of HASMC increased with increasing stiffness of the matrix (Fig 1A). Stiffness increased ROCK activity in these cells (Fig 1B). In addition, PCR showed that stiffness increases ROCK1 mRNA but not ROCK2. Inhibition of ROCK with Fasudil abolished the stiffness induced increase in proliferation.
Conclusion
Our results suggest that stiffness increases proliferation of HASMC via Rho-kinase. Thus, ROCK pathways might be a target to prevent vascular complications of kidney disease.
Funding
- Other NIH Support