Erasmus University Rotterdam
DNA Damage-related Vascular Dysfunction: Pathways and Interventions.
Degree: 2017, Erasmus University Rotterdam
markdownabstractIn my thesis the role of DNA damage on vascular function was studied. DNA damage is one of the primary causes of aging, which is the strongest independent risk factor for chronic diseases such as cancer and cardiovascular diseases. Mice with defective DNA repair are excellent exploration tools because they rapidly reproduce hallmarks of human aging. Most of the studies included in my thesis were performed in mouse models with defects in DNA damage repair, either in all body organs or restricted to vascular endothelium or smooth muscle.
In mice with whole-body defective DNA damage repair I found that phosphodiesterase 1 (PDE1) is increased and this causes impaired nitric oxide signaling; PDE1 is also increased in human senescent vascular smooth muscle cells, and by means of candidate gene look-up analyses, I found that genetic variants in the PDE1A gene were associated with increased diastolic blood pressure and carotid intima media thickness, two hallmarks of human age-related vascular dysfunction. Assessment of cardiovascular function in mice with DNA damage only in the vascular endothelium or smooth muscle revealed that both DNA damage in endothelial cells and in vascular smooth muscle, in what seems to be a cell-autonomous way, lead to specific changes in the vasodilatory pathways that are relevant for aging-related vascular disease. Moreover, interventions such as dietary restriction and phosphodiesterase inhibition improve vascular function in our mouse models of accelerated aging. Overall, my thesis findings bring us one step closer to uncover the mechanisms underlying the association of age and cardiovascular diseases.
to Zotero / EndNote / Reference
APA (6th Edition):
Bautista-Niño, P. (2017). DNA Damage-related Vascular Dysfunction: Pathways and Interventions. (Doctoral Dissertation). Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/103487
Chicago Manual of Style (16th Edition):
Bautista-Niño, Paula. “DNA Damage-related Vascular Dysfunction: Pathways and Interventions.” 2017. Doctoral Dissertation, Erasmus University Rotterdam. Accessed April 26, 2018.
MLA Handbook (7th Edition):
Bautista-Niño, Paula. “DNA Damage-related Vascular Dysfunction: Pathways and Interventions.” 2017. Web. 26 Apr 2018.
Bautista-Niño P. DNA Damage-related Vascular Dysfunction: Pathways and Interventions. [Internet] [Doctoral dissertation]. Erasmus University Rotterdam; 2017. [cited 2018 Apr 26].
Available from: http://hdl.handle.net/1765/103487.
Council of Science Editors:
Bautista-Niño P. DNA Damage-related Vascular Dysfunction: Pathways and Interventions. [Doctoral Dissertation]. Erasmus University Rotterdam; 2017. Available from: http://hdl.handle.net/1765/103487