The new academic year began this week 1. To start the semester off with a bang, CUMC invited Eric Olson, Ph.D of UT Southwestern to come and speak at the annual Samuel Rudin Distinguished Visiting Professor Lectures. Olson spoke about his work on microRNAs (miRs) and their therapeutic possibilities, particularly as heart disease therapies.
Olson reasoned that because miRs have been shown to regulate muscle development and function, perhaps they play a role in regulating our most important muscle, the heart. More specifically, he wondered if disrupting the function of specific miRs could change the response to cardiac assault. In order to determine what miRs may play a role in cardiac function after assault, Olson performed microarray studies. Described in several bodies of work (reviewed here), miR gain- and loss-of-function models appear normal under basal conditions, but are involved in stress-dependent responses. In essence, these miRs play a role in pathological cardiac remodeling only after myocardial injury, and they exhibit differential effects. For example, miR-195 is upregulated in hypertrophic hearts and increased expression of miR-195 is sufficient to drive hypertrophic growth and myocyte disarray, contributing to heart failure. Another miR, miR-126, plays an important role in cardiac repair. Myocardial vascularization is essential following a heart attack, and miR-126 is involved in neoangiogenesis. Without miR-126, proper neovascularization doesn’t occur and vascular rupture ensues.
The possibilities in targeting specific miRs for therapies are virtually endless. Olson described the collaborative development of anti-miRs, which are linked to cholesterol or a long-chain fatty acid to facilitate uptake. If one is able to regulate the expression of a specific miR, it could greatly improve prognosis after cardiac injury. However, these therapies are not without their difficulties. MiRs often regulate more than one target and the pleiotropic effects could outweigh the benefits. Additionally, miRs are rapidly degraded and, although chemical modifications can improve stability, there is not yet consensus in the field on which modification is best.
Nonetheless, I think we will continue to see more development of miR-targeted therapies for cardiovascular disease and other pathologies as this field progresses.
1 Now that the semester has started, the hub calendar should have more events and seminars in the New York area. All Nature Network members are free to post an event or seminar. If you think something is of interest to the New York science community, go ahead and post it!