The role of arginase in the microcirculation in cardiovascular disease

Issue title: Selected post-conference papers of the 38th Conference of the German Society for Clinical Microcirculation and Hemorheology, 21-23 November 2019, Braunschweig, Germany

Guest editors: P. Wiggermann, A. Krüger-Genge and F. Jung

Article type: Research Article

Authors: Wernly, Bernhard^a | Pernow, John^b | Kelm, Malte^c | Jung, Christian^{c; *}

Affiliations: [a] Clinic of Internal Medicine II, Department of Cardiology, Paracelsus Medical University of Salzburg, Salzburg, Austria | [b] Division of Cardiology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden | [c] Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University Düsseldorf, Düsseldorf, Germany

Correspondence: [*] Corresponding author: Christian Jung, M.D., PhD University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf Medical Faculty, Division of Cardiology, Pulmonology and Vascular Medicine Moorenstrasse 5, D-40225 Düsseldorf, Germany. Tel.: +49 211 81 18567; Fax: +49 211 81 18812; E-mail: [email protected].

Abstract: In the microcirculation, the exchange of nutrients, water, gas, hormones, and waste takes place, and it is divided into the three main sections arterioles, capillaries, and venules. Disturbances in the microcirculation can be measured using surrogate parameters or be visualized either indirectly or directly. Arginase is a manganese metalloenzyme hydrolyzing L-arginine to urea and L-ornithine. It is located in different cell types, including vascular cells, but also in circulating cells such as red blood cells. A variety of pro-inflammatory factors, as well as interleukins, stimulate increased arginase expression. An increase in arginase activity consequently leads to a consumption of L-arginine needed for nitric oxide (NO) production by endothelial NO synthase. A vast body of evidence convincingly showed that increased arginase activity is associated with endothelial dysfunction in larger vessels of the vascular tree. Of note, arginase also influences the microcirculation. Arginase inhibition leads to an increase in the bioavailability of NO and reduces superoxide levels, resulting in improved endothelial function. Arginase inhibition might, therefore, be a potent treatment strategy in cardiovascular medicine. Recently, red blood cells emerged as an influential player in the development from increased arginase activity to endothelial dysfunction. As red blood cells directly interact with the microcirculation in gas exchange, this could constitute a potential link between arginase activity, endothelial dysfunction and microcirculatory disturbances. The aim of this review is to summarize recent findings revealing the role of arginase in regulating vascular function with particular emphasis on the microcirculation.

Keywords: Microcirculation, arginase, atherosclerosis, intensive care, intravital microscopy, nitric oxide

DOI: 10.3233/CH-199237

Journal: Clinical Hemorheology and Microcirculation, vol. 74, no. 1, pp. 79-92, 2020