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Young Researchers and Professionals
| Project leader |
Ljubkovic Marko |
| Project co-leader: |
Ulrik Wisloff, PhD |
| Administering organization: |
University of Split School of Medicine |
| Partner Institution/Company: |
Norwegian University of Science and Technology |
| Grant type: |
3B |
| Project title: |
Exercise-induced improvement of chronic heart failure: the role of KATP channels and mitochondria |
| Project summary: |
Chronic heart failure is a clinical syndrome that is characterized by symptoms of shortness of breath, fatigue, fluid retention and a reduced ability to tolerate physical activity. The underlying cause of chronic heart failure is a reduced pumping ability of the heart as a result of structural or functional damage. Almost two thirds of chronic heart failure cases are caused by coronary artery disease and resulting myocardial infarction. Moreover, as human population ages and as more patients survive the myocardial infarction, the prevalence of chronic heart failure in general population is increasing. However, despite the high prevalence of chronic heart failure, an effective therapy is still lacking and patients’ prognosis is poor. Therefore, strategies to improve lifestyle and survival of heart failure patients are of great importance.
Recent studies have found that chronic exercise in patients suffering from postinfarction heart failure significantly increases the pumping ability of the heart and improves patients’ quality of life. However, the mechanism underlying these effects of exercise is still unknown. The goal of the current project entitled “Exercise-induced improvement of chronic heart failure: the role of KATP channels and mitochondria” is to provide a deeper understanding of the mechanisms responsible for the beneficial effects of exercise in chronic heart failure, using a novel approach of investigating the role of yet unrecognized potential contributors (mitochondria and KATP channels). These factors were chosen based on the current knowledge that exercise can affect the function of both the mitochondria, the energy producing organelles within the cell, and KATP channels, important metabolic sensors that couple metabolic demand to the cellular excitability. For that purpose, a rat model of chronic heart failure and a number of state-of-the-art methodologies will be used that will enable identification of the effects of exercise at subcellular and molecular level.
It is expected that this project will provide insight into the complex mechanism whereby exercise improves the function of the diseased heart and that mitochondria and KATP channels will be identified as important contributing factors. The majority of scientific research will be conducted in University of Split Medical School in tight collaboration with Faculty of Medicine at Norwegian University of Science and Technology (Trondheim, Norway) and Medical College of Wisconsin (Milwaukee, USA). Besides their clinical relevance, the results from this project will provide a base for submission of international projects and further extension of international collaboration of the University of Split Medical School. |
| Hrvatski sažetak: |
Kronično zatajenje srca je klinički sindrom koji se manifestira osjećajem nedostatka zraka, umorom, edemima i smanjenom tolerancijom tjelesne aktivnosti, Uzrok kroničnog zatajenja srca je smanjena sposobnost rada srčane crpke, što je posljedica strukturnog ili funkcionalnog oštećenja. U gotovo dvije trećine slučajeva, uzrok kroničnog zatajenja srca je bolest koronarnih arterija i posljedični akutni infarkt miokarda. Također, postupno starenje opće populacije i bolje preživljavanje infarkta miokarda vodi k većoj prevalenciji kroničnog zatajenja srca. Međutim, unatoč visokoj učestalosti kroničnog zatajenja srca, još uvijek ne postoji djelotvorna terapija te je dugoročna prognoza za pacijente loša. Stoga su strategije za unapređenje kvalitete života i bolje preživljavanje bolesnika s kroničnim zatajenjem srca izrazito važne.
Nedavne su studije pokazale da redovita tjelovježba kod bolesnika s postinfarktnim kroničnim zatajenjem srca značajno ojačava sposobnost srca kao crpke i poboljšava kvalitetu života bolesnika. Međutim, mehanizam odgovoran za te učinke je još uvijek nepoznat. Cilj ovoga projekta naslovljenog “Exercise-induced improvement of chronic heart failure: the role of KATP channels and mitochondria” jest omogućiti dublje razumijevanje mehanizama odgovornih za blagotvorne učinke tjelovježbe u kroničnom zatajenju srca, koristeći nov pristup u istraživanju potencijalnih, a još neidentificiranih čimbenika poput mitohondrija ili KATP ionskih kanala. Navedeni su čimbenici odabrani s obzirom na sadašnje spoznaje o utjecaju tjelovježbe na fiziologiju mitohondrija, glavnih unutarstaničnih struktura za proizvodnju energije te na KATP kanale, važne metaboličke senzore koji prilagođavaju staničnu podražljivost metaboličkim zahtjevima stanice. S obzirom na to, predlažemo korištenje štakorskog modela kroničnog zatajenja srca, kao i razne suvremene laboratorijske metode, u svrhu otkrivanja utjecaja tjelovježbe na substaničnoj i molekularnoj razini.
Očekujemo da će ovaj projekt omogućiti nove spoznaje o složenom mehanizmu kojim tjelovježba poboljšava funkciju bolesnog srca te da će mitohondriji i KATP kanali biti prepoznati kao njegove važne sastavnice. Većina će se znanstvene aktivnosti odvijati na Medicinskom fakultetu Sveučilišta u Splitu, s bliskom suradnjom s Faculty of Medicine at Norwegian University of Science and Technology (Trondheim, Norveška) te s Medical College of Wisconsin (Milwaukee, SAD). Osim kliničke važnosti, rezultati ovoga projekta će služiti kao osnova za prijavu međunarodnih projekata i daljnje širenje suradnje Medicinskog fakulteta Sveučilišta u Splitu sa vrhunskim znanstvenicima i institucijama. |
| Amount requested from UKF: |
709.780 HRK |
| Amount of matching funding: |
181.990 HRK |
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