Andreas M. Beyer, PhD
Assistant Professor, Medicine/Cardiology
The Beyer laboratory focuses on the study of small blood vessels that control blood flow to the heart and adipose of humans and the role of these vessels in cardiovascular diseases such as hypertension, coronary artery disease (CAD) and atherosclerosis. Isolated microvessels have shown us that human blood vessels behave much differently than those from animal models.
This work has identified some of the early changes that occur in the development of these maladies.
One of the most prominent findings is that in states of disease the mechanism of flow mediated dilation (FMD) changes from a NO dependent mechanism to a mitochondrial mediated hydrogen peroxide (H2O2) dependent mechanism.
Prior studies have shown that changes in vascular function with aging parallel those associated with disease, with an excess production of reactive oxygen species (ROS) as a key confounding factor. One prominent cause in the development of cellular senescence and tissue aging is shortening of telomeres and reduced telomerase activity. Increased ROS has been shown to cause translocation of telomerase to the cytoplasm decreasing proliferative capacity and telomere length, in turn, resulting in cellular senescence. Early findings suggest that telomerase is one of the key mediators involved in a change of mechanism of FMD, as inhibition of telomerase activity has a similar effect as CAD. Decreased telomere length has been associated with a number of cardiovascular diseases including hypertension and CAD. The consequence of telomere independent effects of telomerase on the mechanism of vascular function is not defined. Recently, telomerase has been linked to mitochondrial maintenance and mtROS production. In fact, animals lacking telomerase are known to develop hypertension though the underlying mechanism, however effects on the vascular system are not known. These findings connect telomerase deficiency, shortened telomeres, oxidative stress and mitochondrial defects into a common pathway whereby disease or stress alter the vasomotor response to physiological stimuli via oxidative stress.
We believe that decreased telomerase activity itself is sufficient to cause vascular defects eventually leading to hypertension and CAD. However, it is not understood how telomerase activity influences mitochondrial ROS production that in turn is a key component of vasodilation associated with aging and disease.
The Beyer lab is using existing pharmacological and genetic tools to study the importance of telomerase in the maintenance of vascular tone in human and rodent microvessels.
The long-term goal is to determine the mechanism by which telomerase activity contributes to cellular and vascular health and to understand the mechanism involved in the change from health to disease leading to further systemic cardiovascular defects. Further, the role of telomerase in the response to external stressors such as obesity, increased salt load, or the existence of other cardiovascular risk factors is being investigated.