The Paolocci Lab has pioneered studies on the in vivo and in vitro cardiovascular actions of nitroxyl (HNO), the one electron-reduction product of nitric oxide (NO), and contrasting HNO effects with those exerted by NO donors and other RNS or ROS such as peroxynitrite and hydroxyl radical. Currently, another main research focus is dedicated to unearthing additional sources of oxidative stress within the myocardium and to assess mitochondrial function/dysfunction in mouse models of CHF, diabetes and obesity.
More specifically, ongoing in vitro and in vivo studies are testing whether and how mitochondrial critically contributes to the generation of ROS/RNS in the diabetic or obese heart, and to evaluate the impact of this phenomenon on myocardial contractility in these diseased conditions. As a separate but mechanistically intermingled line of investigation, members of the PI’s lab are currently evaluating the role of monoamine oxidases (MAO), another major source of ROS, in normal and failing hearts. This focuses on myocardial function, remodeling and survival as well as on cathecolamine cycling and modulation of sympathetic/parasympathetic function.
Potential long-term benefits
Our long-term goal is to better understand the redox-based mechanisms that underlie changes in myocardial structure and function in animal models of congestive heart failure and metabolic syndromes such as diabetes and obesity. In parallel, we aim to develop new redox-based pharmacological tools to enhance myocardial performance and to counter increased oxidative/nitrosative stress in experimental CHF in order to translate this knowledge to human pathology.