No public access
master's thesis
Screening of FDA approved compounds with effect on modification of myofibroblast activation during cardiac remodeling

Kristina Vukušić (2016)
Sveučilište u Rijeci
Odjel za biotehnologiju
Metadata
TitleScreening of FDA approved compounds with effect on modification of myofibroblast activation during cardiac remodeling
AuthorKristina Vukušić
Mentor(s)Miranda Mladinić Pejatović (thesis advisor)
Abstract
Heart failure is the common final evolution of most cardiovascular diseases and is among the leading causes of morbidity and mortality in the developed world. Cardiac remodeling is characterized by cardiac fibroblast differentiation to myofibroblasts. Myofibroblasts are cells that express both collagen and α-SMA and are considered as hallmarks of cardiac remodeling. The general aim of this project is identification of FDA approved drugs able to interfere with two major changes occurring in the remodeling heart connected to poor prognosis, increased collagen deposition by cardiac fibroblasts and the transition from fibroblast to myofibroblast phenotype. Towards this goal, the project has exploited the availability of a High throughput screening facility (HTS) and of a Dual reporter transgenic mouse strain, expressing the EGFP protein under the control of the collagen I-alpha promoter and the RFP protein under the control of the alpha smooth muscle actin promoter (GFP+/RFP+ mouse). The screening assessed the effect of 640 FDA-approved compounds on collagen I alpha and α-SMA expression. The top 10 compounds were further validated in primary fibroblast cultures and in vivo in the GFP+/RFP+ mouse. The obtained preliminary results indicated a potent effect of dexamethasone in decreasing both myofibroblast markers in vitro and in vivo.
Parallel title (Croatian)Probir FDA odobrenih lijekova koji djeluju na modifikaciju aktivacije miofibroblasta tijekom remodeliranja srca
Committee MembersSandra Kraljević Pavelić (committee chairperson)
Miranda Mladinić Pejatović (committee member)
Serena Zacchigna (committee member)
GranterSveučilište u Rijeci
Lower level organizational unitsOdjel za biotehnologiju
PlaceRijeka
StateCroatia
Scientific field, discipline, subdisciplineBIOTECHNICAL SCIENCES
Biotechnology
Study programme typeuniversity
Study levelgraduate
Study programmeBiotechnology in medicine
Academic title abbreviationmag. biotech. in med.
Genremaster's thesis
Language English
Defense date2016-03-15
Parallel abstract (Croatian)
Zatajenje srca je jedan od glavnih uzroka smrti u razvijenom svijetu. Promjena u strukturi srca (remodeliranje srca) nakon ozljede karakterizirana je diferencijacijom fibroblasta u miofibroblaste. Miofibroblasti su stanice koje eksprimiraju kolagen i alpha SMA i smatraju se glavnim pokazateljima promjena u strukturi srca uzrokovanih ozljedom. Cilj ovog istraživanja bio je odabir lijekova, već odobrenih od U.S. Food and Drug Administration (FDA), koji imaju učinak na dvije osnovne promjene koje se događaju prilikom remodeliranja srca, a povezne su sa lošom prognozom bolesti: povećano odlaganje kolagena od strane srčanih fibroblasta i tranzicija fibroblasta u miofibroblaste. U tu svrhu, u istraživanju su korištene metode visokoprotočne stanične analize lijekova za ispitivanje supstanci koje pozitivno utječu na regeneraciju srčanog tkiva, te genetski modificirani životinjski model (miša koji ekspresira zeleni fluorescentni protein (GFP) pod kontrolom kolagenskog promotora i crveni fluorescentni protein (RFP) pod kontrolom aktinskog promotora). U ovom istraživanju testiran je učinak 640 FDA odobrenih lijekova na snižavanje ekspresije kolagena 1 i α-SMA, a lijekovi sa najboljim učinkom odabrani su za daljnje ispitivanje u preliminarnim pokusima in vitro na osnovnoj kulturi fibroblasta i in vivo u GFP+/ RFP + miševima. Dobiveni preliminarni rezultati ukazuju na potencijalni efekt deksametazona u smanjivanju ekspresije kolagen 1 i α-SMA in vivo i in vitro te utjecaj na regeneraciju srčanog tkiva nakon ozljede.
Parallel keywords (Croatian)heart failure fibrosis fibroblasts myofibroblasts FDA compounds dual reporter mouse Zastoj srca fibroza fibroblasti miofibroblasti FDA lijekovi dvojni reporter miš
Resource typetext
Access conditionNo public access
URN:NBNhttps://urn.nsk.hr/urn:nbn:hr:193:483208
CommitterIvana Dorotić