dc.contributor.author
Herrmann, Jaqueline
dc.date.accessioned
2022-09-27T09:24:57Z
dc.date.available
2022-09-27T09:24:57Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/35543
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-35257
dc.description.abstract
Vessel calcifications are a main risk factor for the development of cardiovascular diseases, a leading cause of morbidity and mortality in western societies. Even though vascular calcifications have been researched for centuries, patients still suffer from a huge therapeutic gap, because neither an effective prophylaxis, nor an effective treatment is available. Currently, consent exists that vascular calcification is an active cellular process that resembles bone formation. Vascular Smooth Muscle Cells (VSMCs) and their transdifferentiation into osteoblast like cells are considered decisive in the formation of vascular calcifications. Several stimuli can induce osteoblastic transdifferentiation, including cellular aging processes, oxidative stress and inflammation. These factors can be linked into a concept termed inflammaging via the formation of damage associated molecular patterns, persistent DNA damage and induction of a senescence associated secretory phenotype.
The objective of this dissertation was to analyse the effects of the cellular stressors Azathioprine and Doxorubicin and the pro-inflammatory cytokine interleukin 1ß on the induction of osteoblastic transdifferentiation of VSMCs and vascular calcification in different experimental settings. The cellular stressors induce the formation of reactive oxygen species, cellular senescence, secretion of pro-inflammatory cytokines such as interleukin 1ß and interleukin 6, upregulation of NLRP3 inflammasome components as well as osteoblastic transdifferentiation and calcification of VSMCs. Stimulation with interleukin 1ß induced a pro-inflammatory auto-loop, osteoblastic transdifferentiation and calcification of VSMCs, but did not induce markers of senescence in VSMCs apart from components of the cellular senescence associated secretory phenotype. For both, cellular stressors and interleukin 1ß, the NLRP3 inflammasome is decisively involved in the calcification process, as inhibition of NLRP3 significantly reduces the calcification induced by cellular stressors and interleukin 1ß.
This dissertation is in line with other recent research that emphasizes the involvement of inflammaging in the pathology of vascular calcification. Several therapeutic targets arise from the insight that oxidative stress, inflammation and senescence are crucially involved in the pathophysiology of VSMC calcification. These new therapeutic approaches can help to meet the high unmet clinical need of patients suffering from vascular calcifications.
en
dc.format.extent
X, 133 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
vascular calcification
en
dc.subject
inflammation
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::615 Pharmakologie, Therapeutik
dc.title
Pathophysiology of Vascular Calcification: Mechanisms and Therapeutic Options
dc.contributor.gender
female
dc.contributor.firstReferee
Tölle, Markus
dc.contributor.furtherReferee
Parr, Maria Kristina
dc.date.accepted
2022-06-24
dc.identifier.urn
urn:nbn:de:kobv:188-refubium-35543-2
dc.title.translated
Pathophysiologie der vaskulären Kalzifizierung: Mechanismen und Therapieoptionen
de
refubium.affiliation
Biologie, Chemie, Pharmazie
dcterms.accessRights.dnb
free
dcterms.accessRights.openaire
open access