Grant: Operating Grant

Vascular diseases, such as hypertension and atherosclerosis, result from abnormal functions of a major cell type in the blood vessels, called smooth muscle cells. Myocardin is a protein molecule in smooth muscle cells that controls the levels of proteins responsible for muscle contraction. Lower activity of myocardin will result in less contractile proteins in smooth muscle cells, and these cells will lack the ability to contract in response to various factors. They will even grow to form lesions in the blood vessel wall. Therefore, it is very important to study how myocardin activity is regulated. If we understand this, we will be able to develop a way to control vascular disease. What we have discovered in our laboratory is that myocardin must be degraded through a special system, called the ubiquitin-proteasome system, to gain its activity. We called this process "Degradation-Activation", which is novel for myocardin in smooth muscle. In the current application, we propose to investigate the Degradation-Activation mechanism for myocardin. By targeting myocardin, our study will help develop a novel therapeutic approach to vascular disease.