The research in my laboratory is dedicated to a better understanding of the mechanisms of injury and adaptation in the vasculature, focusing on pathways related to oxidative stress and nitric oxide metabolomics.
Oxidants that are derived from oxygen regulate cardiovascular function and increase oxidative stress within the vasculature is as an important contributor to cardiovascular disease. The mechanisms relating oxidative stress to vascular disease are yet to be fully understood and these include promotion of vascular inflammation and remodeling as well as inactivation of nitric oxide (NO). Nitric oxide is a small gaseous signaling molecule that regulates many aspects of cardiovascular physiology and disease including blood pressure and inflammation.
Within this area, special attention is directed towards hemoproteins as important modulators of oxidative stress and NO bioavailability. We have focused our attention on cytoglobin (CYGB), a member of the globin vertebrate family with poor functional annotation. We have characterized CYGB in intact vessels and vascular smooth muscle cells as an adaptive response that may confer protection against injury in the vasculature. Mechanisms through which the cytoprotective effect of CYGB may arise (for example vasodilatory, anti-apoptotic, and anti-inflammatory actions) are explored and the involvement of NO and oxidant scavenging capacity in contributing to such cytoprotection is examined..
Our laboratory also pursues the theme of injury and adaptation in the context of mechanisms that contribute to arteriovenous fistula failure in end-stage renal disease. We use - among other things - approaches based on transgenic models of arteriovenous fistula failure and human tissues from control and disease settings from which primary cell cultures might be derived and studied. These studies are part of collaborative efforts between the Center for Cardiovascular Sciences and the Nephrology Group at AMC.
Finally, our laboratory collaborates with other initiatives at AMC and in the Greater Capital Region that explore oxidants and NO physiology and pathophysiology in the context of stroke, cancer, and asthma. We provide expertise in nitric oxide metabolomics to assist our collaborators and other investigators in determining changes in the nitric oxide pathway.
Techniques from chemistry to vascular physiology are being used:
- Free radical biochemistry: spectroscopic, chemiluminescence, and electrochemical methods and kinetic studies for the determination of reactive oxygen and nitrogen species.
- Molecular biology: cloning, mutagenesis, adenoviral and lentiviral expression systems.
- Cell biology: mammalian transfection, dual-emission fluorescence microscopy, laser scanning confocal fluorescence microscopy.
- Physiology: vasoreactivity studies of small and large arteries; animal models of vascular injuries and cardiovascular disease.
Inflammation and Oxidative Stress in Cardiovascular Disease.
Vascular Smooth Muscle Biology.