Letter from the Editor

Dr. Paul Matsudairas
Professor: Biology, Biological Engineering; Member, Whitehead Institute
Massachusetts Institute of Technology, Cambridge MA 02139

 

 

Cardiovascular diseases are the leading cause of death in the world. Unfortunately, current therapies to treat these diseases are only moderately effective, often due to accelerated vascular diseases resulting from the effects of injurious mechanical interventions for opening occluded arteries. During mechanical interventions, the endothelium, the monolayer of cells lining the blood vessel, is injured. The endothelium produces a variety of compounds that regulate normal vascular function. These compounds are especially important in controlling vascular repair after injury, and their loss can hasten obstructive vascular diseases or lead to rapid reocclusion of the artery after interventional procedures. By coupling molecular biological modification of cells with the technology of tissue engineering, we can identify which compounds may be contributing to the endothelial regulation of vascular injury. These data may not only change our view of vascular biology, but offer new methods for treating vascular disease. Mechanical interventions to relieve atherosclerosis can often lead to accelerated vascular disease called restenosis. These diseases are a biologic response to vascular injury, characterized by thrombosis, inflammation, smooth muscle cell migration and proliferation into the blood vessel, and extracellular tissue growth. Tissue engineered endothelial cell implants inhibit restenosis in animal models of vascular injury via secretion of biochemical compounds. Identification of the endothelial compounds that regulate the vascular response to injury is a crucial step toward elucidating the cellular and molecular mechanisms underlying restenosis as well as toward developing therapies for restenosis. Nitric oxide appears to play a critical role in maintaining vascular homeostasis. This study seeks to determine the role of nitric oxide in the ability of tissue engineered endothelial cell implants to regulate the vascular response to injury via inhibition of smooth muscle cell proliferation. Using an in vitro co-culture system, smooth muscle cells will be grown in the presence of tissue engineered endothelial cells with modulated nitric oxide levels, in order to determine the effect on smooth muscle cell proliferation. This study will also examine the relative roles that nitric oxide and heparan sulfate proteoglycans play in regulating smooth muscle cell proliferation. Heparan sulfate proteoglycans are another endothelial-derived product known to have antiproliferative properties. By controlling the amount of active proteoglycan and nitric oxide secreted from the endothelial cells, this model will be used to dissect the mechanisms through which endothelial cells can regulate vascular injury.

MIT