Frane Runjić
Ime i prezime: dr. sc. Frane Runjić
Naslov disertacije: “PROMJENE UPALNIH BILJEGA I PAD SRČANE MITOHONDRIJSKE AKTIVNOSTI U BOLESNIKA S KORONARNOM ARTERIJSKOM BOLESTI I BLAGOM SISTOLIČKOM DISFUNKCIJOM”
Mentorica: prof. dr. sc. Jasna Marinović Ljubković
Datum obrane: 2. Studenoga 2023.
Poveznnica:
https://repozitorij.mefst.unist.hr/islandora/object/mefst%3A2190/datastream/PDF/view
Kvalifikacijski znanstveni radovi za doktorsku disertaciju:
Runjic F, Martinovic-Kaliterna D, Salamunic I, Kristic I, Ljubkovic M, Marinovic J. Association of anticardiolipin antibodies, complement and leptin with the severity of coronary artery disease expressed as syntax score. J Physiol Pharmacol. 2020;71(3).
https://doi.org/10.26402/jpp.2020.3.09
Ljubkovic M,
Runjic F, Bulat C, Cavar M, Frankovic L, Marovic Z, Bilopavlovic N, Marinovic J. Assessment of mitochondrial respiratory capacity in relation to cardiac contractile performance in patients with normal to mildly decreased cardiac systolic function. J Physiol Pharmacol. 2022;73(6).
https://doi.org/10.26402/jpp.2022.6.05
SAŽETAK:
Cilj istraživanja: Svrha ovih istraživanja bila je utvrditi povezanost između kompleksnosti koronarne arterijske bolesti i proupalnih čimbenika u obliku antikardiolipinskih protutijela, kao i utvrditi povezanost između globalne sistoličke funkcije lijeve klijetke i parametara mitohondrijske respiracije.
Materijali i metode: Provedena su opservacijska, presječna, klinička znanstvena istraživanja. Obuhvaćeno je ukupno 65 odraslih bolesnika koji su podvrgnuti invazivnoj koronarografiji zbog sumnje na koronarnu arterijsku bolest (prvo istraživanje) i 40 odraslih bolesnika koji su podvrgnuti elektivnoj kardiokirurškoj revaskularizaciji miokarda zbog značajne koronarne arterijske bolesti (drugo istraživanje). Svi ispitanici podvrgnuti su detaljnoj anamnezi, fizikalnom pregledu i ehokardiografskim mjerenjima. Ispitanici iz drugog istraživanja su interaoperacijski podvrgnuti biopsiji miokarda, te naknadnim eksperimentalnim procjenama mitohondrijske funkcije u tkivu miokarda.
Rezultati: Utvrđena je neovisna statistički značajna pozitivna korelacija kompleksnosti koronarne arterijske bolesti i antikardiolipinskog protutijela aCL-IgG (β 5,58, P=0,005), dok nije bilo neovisne povezanosti između kompleksnosti koronarne arterijske bolesti i ostalih odabranih varijabli (aCL-IgG, leptin, C3, C4) nakon prilagodbe za dob, indeks tjelesne mase i koncentracije glukoze i kolesterola u krvi. Nadalje, utvrđena je statistički značajna pozitivna korelacija između maksimalne mitohondrijske respiracije u tkivu miokarda i ejekcijske frakcije lijeve klijetke (r=0,37, P=0,020), što je potvrđeno nakon prilagodbe za zbunjujuće varijable (β 0,11, P=0,030). Slično tome, utvrđena je statistički značajna pozitivna korelacija između ejekcijske frakcije lijeve klijetke i izražaja glavnih enzima oksidacije masnih kiselina. S druge strane, nije utvrđena značajna povezanost između srčane sistoličke funkcije i indikatora mitohondrijske količine u tkivu, niti razine pojedinih respiratornih komplekasa. Također, nije nađena značajna korelacija između srčane sistoličke funkcije i mitohondrijskog kapaciteta za oksidaciju ugljikohidrata.
Zaključci: Razine antikardiolipinskog aCL-IgG protutijela su značajno povezane sa kompleksnosti koronarne arterijske bolesti u obliku SYNTAX zbroja, dok ista veza ne postoji s ostale medijatore upale poput antikardiolipinskog protutijela aCL-IgM, komponenti komplementa C3 i C4, te leptina. Također, kod pacijenata u ranim fazama patološkog remodeliranja miokarda i blago smanjenom sistoličkom funkcijom, postoji veza između LVEF i mitohondrijske respiratorne sposobnosti te kapaciteta oksidacije masnih kiselina.
SUMMARY:
Doctoral dissertation title: “CHANGES IN INFLAMMATORY MARKERS AND REDUCED CARDIOMYOCYTE MITOCHONDRIAL ACTIVITY IN PATIENTS WITH CORONARY ARTERY DISEASE AND MILD SYSTOLIC DYSFUNCTION”
Objectives: The aim of this study was to determine the relationship between the complexity of coronary artery disease and pro-inflammatory factors in the form of anticardiolipin antibodies, as well as to determine the relationship between global left ventricular systolic function and mitochondrial respiration parameters.
Materials and methods: An observational, cross-sectional, clinical research was conducted. A total of 65 adult patients who underwent invasive coronary angiography due to suspected coronary artery disease (first study) and 40 adult patients who underwent elective surgical myocardial revascularization due to significant coronary artery disease (second study) were included. All subjects underwent a detailed medical history, physical examination and echocardiographic measurements. Subjects from the second study underwent intraoperative
myocardial biopsy, which was followed by subsequent experimental assessments of mitochondrial function in biopsied myocardial tissue.
Results: An independent statistically significant positive correlation of the complexity of coronary artery disease (SYNTAX score) and anticardiolipin antibody aCL-IgG was determined (β 5.58, P=0.005), while there was no such association for other selected variables (aCL-IgG, leptin, C3, C4) after adjusting for age, body mass index, glucose and cholesterol levels. Furthermore, a statistically significant positive correlation was found between maximal mitochondrial respiration in myocardial tissue and left ventricular ejection fraction (r=0.37, P=0.020), which was confirmed after adjustment for confounding variables (β 0.11, P =0.030). Similarly, a statistically significant positive correlation was found between the left ventricular ejection fraction and the expression of the main fatty acid oxidation enzymes. On the other hand, no significant correlation was found between cardiac systolic function and indicators of mitochondrial quantity in the tissue, nor the level of individual respiratory complexes. Also, no significant correlation was found between cardiac systolic function and mitochondrial capacity for carbohydrate oxidation.
Conclusions: Anticardiolipin aCL-IgG antibody levels are significantly related to the complexity of coronary artery disease in the form of SYNTAX score, while the same relationship does not exist with other mediators of inflammation such as anticardiolipin antibody aCL-IgM, complement components C3 and C4, and leptin. Also, in patients in the early stages of pathological remodeling of the myocardium and slightly reduced systolic function, there is a relationship between LVEF and mitochondrial respiratory ability and fatty acid oxidation capacity.
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