PhD defence K. (Keivan) Golshiri

Summary:

Cardiovascular diseases (CVDs) are by far the leading cause of death in the world, causing one-third of all deaths worldwide and accounting for trillions of dollars of healthcare expenditure. Apart from the long-lasting impact of classical cardiovascular risk factors, such as smoking, obesity, dyslipidemia and hypertension, on the vasculature, chronological age remains the single most important determinant of cardiovascular problems. Hence, it is needed to study age- and non–age-related aspects of vascular ageing and their interaction, in order to fully understand and combat cardiovascular disease and its comorbidities. The cyclic nucleotide phosphodiesterases (PDEs) constitute a group of enzymes with a key role in regulating the amplitude, duration and compartmentalization of cyclic nucleotide signaling by degradation of the phosphodiester bond in these second messengers. In this thesis, we mainly investigated the effects of PDE inhibition on vascular aging features caused by DNA damage. Besides this, some potential interventions to prevent or reverse DNA damage-related vascular dysfunction have been evaluated.