Mitochondrial function and the role of reactive oxygen species in microvascular skeletal muscle endothelial cells derived from rat and human. Microvascular endothelial cells – Beauty or the Beast?

Research output: Book/ReportPh.D. thesis

Cardiovascular disease is highly prevalent and associated with the highest mortality rate in the Western world. Impaired function of endothelial cells, located on the inside of all blood vessels, is one of the main causes of cardiovascular disease. It has been proposed, that individuals with cardiovascular disease have impaired mitochondrial function and increased mitochondrial formation of reactive oxygen species (ROS), but evidence for this proposition is lacking. Enhanced ROS formation in endothelial cells is critical, as ROS readily react with and inactivate nitric oxide (NO), a key player in the control of vascular tone. Enhanced knowledge of mitochondrial function and ROS formation in cardiovascular disease is important for the molecular understanding of endothelial dysfunction and for the development of novel treatment strategies in cardiovascular disease. This thesis focuses on hypertension and addresses the role of mitochondria in endothelial dysfunction with a specific focus on redox balance, NO bioavailability and metabolism in skeletal muscle microvascular endothelial cells. The studies of this thesis include data on primary endothelial cells isolated from skeletal muscle of both rats and humans, as well as data from an invivo human study, in which the impact of regular exercise training was assessed. Moreover, to assess the role of mitochondria derived ROS for endothelial phenotype and function, cells were subjected to chronic treatment with the mitochondrial antioxidant, Mitoquinone mesylate (MitoQ).

Main findings in this thesis were that hypertension was associated with elevated
mitochondrial ROS (Study II and Study IV) with an associated lower availability of NO in skeletal muscle microvascular endothelial cells (Study II). The higher ROS production from the mitochondria in human endothelial cells in patients with hypertension correlated with endothelial function determined in vivo by acetylcholine infusion (Study III). Finally, there was an improved redox balance and potential for prostaglandin synthesis with exercise training and with MitoQ
treatment. These interventions were also associated with a reduction in glycolytic metabolism in the endothelial cells.

In conclusion, this thesis has for the first time established that, in hypertension, skeletal muscle derived microvascular endothelial cells present a higher mitochondrial ROS formation, lower antioxidant levels and a consequent lower NO bioavailability. Exercise training and treatment with MitoQ can ameliorate this redox imbalance. Future studies should provide further insight into the specific molecular signalling pathways underpinning these regulatory mechanisms.
Original languageEnglish
Place of PublicationCopenhagen
PublisherDepartment of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen
Number of pages163
Publication statusPublished - 2022

    Research areas

  • Faculty of Science - Mitochondrial function, Microvascular endothelial cells, Rat, Human

ID: 300916314