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doctoral thesis
IZRAŽAJ BJELANČEVINE TOPLINSKOG ŠOKA HSP60 I RECEPTORA TLR2 I TLR4 U MIOKARDU SRCA S HIPERTROFIJOM LIJEVE KLIJETKE
2021. urn:nbn:hr:184:289587
Ferenčić, Antun
University of Rijeka
Faculty of Medicine
Department of Forensic Medicine and Criminalistics

Cite this document

Ferenčić, A. (2021). IZRAŽAJ BJELANČEVINE TOPLINSKOG ŠOKA HSP60 I RECEPTORA TLR2 I TLR4 U MIOKARDU SRCA S HIPERTROFIJOM LIJEVE KLIJETKE (Doctoral thesis). Rijeka: University of Rijeka, Faculty of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:184:289587

Ferenčić, Antun. "IZRAŽAJ BJELANČEVINE TOPLINSKOG ŠOKA HSP60 I RECEPTORA TLR2 I TLR4 U MIOKARDU SRCA S HIPERTROFIJOM LIJEVE KLIJETKE." Doctoral thesis, University of Rijeka, Faculty of Medicine, 2021. https://urn.nsk.hr/urn:nbn:hr:184:289587

Ferenčić, Antun. "IZRAŽAJ BJELANČEVINE TOPLINSKOG ŠOKA HSP60 I RECEPTORA TLR2 I TLR4 U MIOKARDU SRCA S HIPERTROFIJOM LIJEVE KLIJETKE." Doctoral thesis, University of Rijeka, Faculty of Medicine, 2021. https://urn.nsk.hr/urn:nbn:hr:184:289587

Ferenčić, A. (2021). 'IZRAŽAJ BJELANČEVINE TOPLINSKOG ŠOKA HSP60 I RECEPTORA TLR2 I TLR4 U MIOKARDU SRCA S HIPERTROFIJOM LIJEVE KLIJETKE', Doctoral thesis, University of Rijeka, Faculty of Medicine, accessed 04 December 2024, https://urn.nsk.hr/urn:nbn:hr:184:289587

Ferenčić A. IZRAŽAJ BJELANČEVINE TOPLINSKOG ŠOKA HSP60 I RECEPTORA TLR2 I TLR4 U MIOKARDU SRCA S HIPERTROFIJOM LIJEVE KLIJETKE [Doctoral thesis]. Rijeka: University of Rijeka, Faculty of Medicine; 2021 [cited 2024 December 04] Available at: https://urn.nsk.hr/urn:nbn:hr:184:289587

A. Ferenčić, "IZRAŽAJ BJELANČEVINE TOPLINSKOG ŠOKA HSP60 I RECEPTORA TLR2 I TLR4 U MIOKARDU SRCA S HIPERTROFIJOM LIJEVE KLIJETKE", Doctoral thesis, University of Rijeka, Faculty of Medicine, Rijeka, 2021. Available at: https://urn.nsk.hr/urn:nbn:hr:184:289587

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TitleIZRAŽAJ BJELANČEVINE TOPLINSKOG ŠOKA HSP60 I RECEPTORA TLR2 I TLR4 U MIOKARDU SRCA S HIPERTROFIJOM LIJEVE KLIJETKE
Title (english)EXPRESSION OF HEAT SHOCK PROTEIN HSP60 AND TLR2 AND TLR4 RECEPTORS IN THE MYOCARD OF THE HEART WITH LEFT VENTRICULAR HYPERTROPHY
AuthorAntun Ferenčić
MentorDražen Cuculić (mentor)
MentorHrvoje Jakovac (komentor)
Committee memberZlatko Trobonjača (predsjednik povjerenstva)
Committee memberVedrana Petrovečki (član povjerenstva)
Committee memberDražen Kovač (član povjerenstva)
GranterUniversity of Rijeka
Faculty of Medicine
(Department of Forensic Medicine and Criminalistics)
Rijeka
Defense date and country2021-11-02, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Clinical Medical Sciences
Forensic Medicine
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Clinical Medical Sciences
Pathophysiology
Universal decimal classification
(UDC)		61 - Medical sciences
Abstract
Cilj istraživanja: Cilj istraživanja je bio utvrditi dolaze li do pojačanog izražaja HSP60, TLR2 i TLR4 kod ljudi s patološki uvećanom lijevom srčanom klijetkom i na taj način doprinijeti rasvjetljavanju molekulskih zbivanja tijekom hipertrofije srčanog mišića te inicijalnih procesa uključenih u patogenezu njenih posljedica. Takvo bi istraživanje dokazalo da je stečena hipertrofija lijeve klijetke čovjeka posredovana humoralnom imunosti, što se do sada samo pretpostavljalo, budući da su dosadašnje studije na tu temu rađene isključivo na životinjskim modelima. Materijali i metode: U tu svrhu izvršene su analize imunohistokemijskog izražaja na uzorcima tkiva srčanog mišića dobivenima tijekom obdukcija ljudi u kojih je hipertrofija lijeve klijetke bila jedini patološki nalaz i kod kojih je kao neposredni uzrok smrti određena iznenadna srčana smrt. Uzorci iz kontrolne skupine dobiveni su od ispitanika kod kojih histološki nije pronađena srčana patologija, a koji su umrli nasilnom smrću (nesretni slučaj ili samoubojstvo). Za ispitivanje translokacije HSP60 korištena je dvostruka imunoflorescencija, dok je interakcija HSP60 i TLR2/4 dokazivana testom neposrednog vezivanja (PLA). Rezultati: Rezultati su pokazali značajno veći izražaj HSP60, TLR2 i TLR4 u hipertrofičnom srčanom mišiću u usporedbi s normalnim. Nadalje, u hipertrofičnim smo kardiomiocitima pronašli membransku translokaciju HSP60 i znakove interakcija HSP60/TLR. Korelacijska je analiza pokazala vrlo značajne međukorelacije između kvantificiranih vrijednosti intenziteta imunohistokemijskog bojenja HSP60, TLR2 i TLR4 kod ispitanika s hipertrofijom lijeve klijetke, dok u kontrolnoj skupini rezultati nisu pokazali značajne korelacije. Rezultati dobiveni PLA analizom jasno su pokazali da se HSP60 u hipertrofičnom srčanom mišiću veže za TLR2 i TLR4. Zaključci: Između sekundarno hipertrofiranog i normalnoga srčanog mišića lijeve srčane klijetke čovjeka postoje razlike u izražaju HSP60, TLR2 i TLR4. Osim toga, dobiveni podatci ukazuju na važnu potpornu ulogu HSP60 u adaptivnom rastu kardiomiocita, dok istodobna indukcija TLR2 i TLR4 predlaže interakcije HSP60-TLR kao rana molekulska zbivanja kod sekundarne hipertrofije lijeve klijetke.
Abstract (english)
Objectives: The study aimed to determine whether HSP60, TLR2 and TLR4 are overexpressed in people with pathologically enlarged left ventricles and thus contribute to the elucidation of molecular events during myocardial hypertrophy and the initial processes involved in its pathogenesis. Such research would prove that acquired left ventricular hypertrophy is mediated by humoral immunity, which has so far only been hypothesized, given that previous studies on this topic have been done exclusively on animal models. Material and methods: For this reason, immunohistochemical expression analyzes were performed on myocardial tissue samples acquired during autopsies of people in whom left ventricular hypertrophy was the only pathological finding and in whom sudden cardiac death was determined as the immediate cause of death. Samples from the control group were obtained from subjects who were not found to have cardiac pathology and who died a violent death (accident or suicide). Double immunofluorescence was used to examine the HSP60 translocation, while the interaction of HSP60 and TLR2/4 was demonstrated by a direct ligation test (PLA). Results: The results showed significantly higher expression of HSP60, TLR2, and TLR4 in the hypertrophic myocardium compared to the normal myocardium. Moreover, we found HSP60/TLR interactions in hypertrophic cardiomyocytes. Correlation analysis showed very significant intercorrelations between quantified values of HSP60, TLR2, and TLR4 immunohistochemical intensities in subjects with left ventricular hypertrophy while in the control group the results showed no significant correlations. The results obtained by PLA analysis clearly showed that HSP60 in hypertrophic myocardium binds to TLR2 and TLR4. Conclusion: There are differences in the expression of HSP60, TLR2, and TLR4 between the secondary hypertrophied myocardium and the normal left ventricular myocardium. In addition, the data obtained indicate an important supporting role of HSP60 in adaptive cardiomyocyte growth, while concomitant induction of TLR2 nad TLR4 suggests HSP-TLR interactions as early molecular events in secondary left ventricular hypertrophy.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:184:289587
Promotion2022
Study programmeTitle: Biomedicine Postgraduate (doctoral) study programme
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
Type of resourceText
File originBorn digital
Access conditionsAccess restricted to students and staff of home institution
Terms of useLicence In copyright icon
Created on2022-07-08 08:20:48