| dc.description.abstract | Inflammation is a critical mechanism for the development of cardiovascular disease (CVD), and it is thought that central to its impact is endothelial dysfunction. Nitric oxide (NO) is antiinflammatory and improves vascular function in patients with established CVD, and endothelial dysfunction and can be augmented by enhancing the non-canonical pathway through dietary supplementation with inorganic nitrate (NO3-). Women are an underrepresented group in cardiovascular clinical trials, and data suggests that CVD affects almost as many women as men. Separately, it has been reported that there are sex differences in the incidence and severity of COVID-19-related adverse cardiovascular events. Mechanisms describing this are lacking, and similarly to CVD, endothelial dysfunction and the depletion of NO seem to be central themes for the development of cardiovascular complications. The clinical studies presented in this thesis are designed to investigate whether dietary NO3- or sex influences inflammatory responses and vascular function in models of vaccineinduced endothelial dysfunction in healthy volunteers. In addition, the effects of dietary NO3- on in-stent restenosis (ISR) in patients who have previously undergone PCI for CAD are shown. Our findings support that typhoid and COVID-19 vaccines induce systemic inflammation and endothelial dysfunction in men. This is not observed in men treated with dietary NO3-. Mechanistically, this appears to be related to changes in monocyte populations and the expression of the cellular adhesion molecules on T-cells. Women seem to be protected from vascular dysfunction following typhoid and COVID-19 vaccination, regardless of dietary NO3- treatment or placebo. Finally, we observed that dietary NO3- reduces the rate of ISR, evaluated by quantitative coronary angiography, in patients with established CAD who have previously undergone PCI for stable angina. This effect was observed in men but not in women. | en_US |
