Naslov
Left ventricular hypertrophy is associated with overexpression of HSP60, TLR2, and TLR4 in the myocardium

Autori
Ferenčić, Antun ; Cuculić, Dražen ; Stemberga, Valter ; Šešo, Bernard ; Arbanas, Silvia ; Jakovac, Hrvoje

Izvornik
Scandinavian Journal of Clinical and Laboratory Investigation (0036-5513) 80 (2020), 3; 236-246

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
HSP60 ; Myocardial hypertrophy ; TLR2 ; TLR4 ; cardiomyocytes ; overexpression.

Sažetak
Left ventricular hypertrophy is a common adaptive response to increased cardiac workload. Cardiomyocytes growth and increase in contractile force are conditioned by sufficient energy production, which implies appropriate mitochondrial function. The 60 kDa heat shock protein (HSP60) is a chaperone essential for mitochondrial proteostasis, but when translocates from mitochondria, it can also act as a potent inflammatory mediator binding to toll-like receptors (TLRs). In this study, we aimed to compare the expression pattern of HSP60, TLR2, and TLR4 in hypertrophic vs non-hypertrophic, normal human myocardium. We further examined whether HSP60 in situ binds to TLRs in hypertrophic myocardial tissue. In addition, expression of activated downstream targets of TLR 2/4 pathways was also evaluated.For this purpose, immunohistochemical expression analyses were performed on myocardial tissue samples obtained during the autopsy of human subjects in which left ventricular hypertrophy was the only cardiopathological finding and had died from sudden cardiac death, as well as from the subjects without any cardiac pathology, that died by unnatural death (accident or suicide). Double immunofluorescence was used to examine HSP60 translocation, while proximity ligation assay (PLA) was performed to assess HSP60 and TLRs interactions.Hypertrophic myocardium showed significantly higher expression of HSP60, TLR2, and TLR4 compared to normal myocardium. Furthermore, in hypertrophic cardiomyocytes, we found membrane translocation of HSP60 and signs of HSP60/TLR interactions.Conclusion: The obtained data point to an important supportive role of HSP60 in adaptive cardiomyocytes growth, while concomitant induction of TLR2 and TLR4 candidates HSP60-TLRs interactions as an early events during pathogenesis of secondary complications consequently to the left ventricular hypertrophy.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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