<H3 class=subhead>Aiming to Help the Heart Create Its Own Coronary Bypass</H3>
<DIV class=photobox><IMG class=imagecache-220 title="Coronary Angiogensis Illustration" alt="Coronary Angiogensis Illustration" src="/sdmpubfiles/CoronaryAngiogensis.png"><BR>
<DIV class=caption>Conceptualization of angiogenic gene therapy, showing growth of collateral vessels around the occlusion.<BR>
<DIV class=byline>Illustration by Kathleen Gebhart, Media Services</DIV></DIV></DIV>
<P>Arteriogenesis is the development of mature blood vessels supported by smooth muscle. This natural process usually occurs in response to occlusion (blockage) of blood flow within a vessel, and results in the formation of collateral vessels that bypass the blockage, thus allowing blood flow to return to the affected area.</P>
<P>Arteriogenesis has the potential to lessen the impact of myocardial infarction (heart attack), and thereby reduce the effects of heart disease, which is the leading cause of death in the United States.</P>
<P>Unfortunately, arteriogenesis has two major drawbacks. First, vessel formation takes a significant amount of time. Often the slow process results in catastrophic injury before the collateral system is in place. Secondly, even in the event of successful collateral formation, only 30% to 40% of the original blood flow capacity is restored.</P>
<P>The research team directed by Todd K. Rosengart, MD, is now conducting basic and translational studies that aim to shed light on the underlying process of arteriogenesis in order to overcome these limitations.</P>
<P>Dr. Rosengart's research focuses primarily on the early growth response (Egr-1) gene. Current research suggests that this gene is among the first activated in response to the physical stimuli, such as increased arterial pressure and fluid shear stress, which accompany occlusion.</P>
<DIV class=callout>
<P>Research that, hopefully, can be translated into gene therapy to stimulate the heart's growth of <br>
new blood vessels — to create a "biologic" coronary bypass.</P></DIV>
<P>Egr-1 is also known to regulate many processes crucial to vessel formation such as endothelial cell proliferation and monocyte/macrophage recruitment to the occlusion site. Research into this gene may resolve how the body translates physical stimuli into genetic pathways that regulate arteriogenesis.</P>
<P>Dr. Rosengart comments: "Ultimately, through the modulation of Egr-1 and its target genes, we hope to improve the body's response time to occlusion, as well as to increase the final blood-flow capacity of the collateral network formed by this process. The great potential to save lives offered by such therapy makes it an extremely exciting pursuit for our research team."</P>
<P>Robert Gersch, PhD, research assistant professor of surgery, who is the basic and translational research scientist in charge of Dr. Rosengart's laboratory, explains:</P>
<P>"Research now underway in our lab involves cellular analysis as well as a femoral ligation model. We hope to study Egr-1's role in arteriogenesis by altering its expression level in these systems and comparing the reaction to occlusion in the treatment groups with a normal control group.</P>
<P>"Future work will focus on a myocardial ischemia model in which the slow occlusion build-up observed in heart disease is mimicked. By using this model, we can target and modulate the expression of Egr-1 and its target genes with the goal of improving the arteriogenic response."</P>
<P>Dr. Rosengart's arteriogenesis lab is currently supported by the National Institutes of Health — it is one of only 25 NIH-funded cardiac surgery labs of its kind in the country — and his research team includes both residents and students, in addition to Dr. Gersch.</P>
