Smooth muscle cell differentiation, variability, and phenotypic alteration with disease

Smooth muscle cells (SMCs) play crucial roles in vascular development and vascular homeostasis, and have been implicated in diseases such as hypertension, atherogenesis, and post-angioplasty restenosis. De-differentiation and phenotypic modulation of SMCs contribute to atherosclerosis. In the adult vessel, injury appears to reverse the developmental differentiation process, with SMCs proliferating and displaying a migratory, invasive phenotype. Despite the importance of this process, little is known about the mechanisms that regulate the differentiation and de-differentiation of vascular SMCs. Further understanding of these fundamental processes may provide insight into the development and progression of vascular disease. Also, information regarding the contribution of SMCs to the maturation of the blood vessel wall will help realize the potential for therapeutic angiogenesis as a treatment for ischemic vascular disease.

Using a variety of approaches, we are seeking to identify the master regulatory genes responsible for the differentiation of vascular SMCs as well as genes associated with the atherosclerotic process. Primary culture studies of human SMCs using gene microarrays are elucidating tissue subtype-specific genes and revealing candidate genes that may play roles in phenotypic modulation in the diseased state. Multipotent cell-lines from the mouse are being induced to differentiate along the smooth muscle cell lineage, and oligonucleotide microarrays are probing the cells during differentiation to identify candidate regulatory genes responsible for smooth muscle cell determination and differentiation, with an emphasis on early transcription factors. SMCs derived from normal and diseased human vessels are also being extracted and examined.

Other Research Areas:

- Overview
- Athero
  disease
- Endothelial
  cells
- Smooth
  muscle
  cells
- Cell
  remodeling
- Apelin
- Gene
  Hunting
- SAPPHIRe
- Heart 
  developing

People involved in this project:

- Josh