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

Autor: Dražen Cuculić, Valter Stemberga, Antun Ferenčić, Bernard Šešo, Hrvoje Jakovac, Silvia Arbanas
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Clinical Biochemistry
cardiomyocytes
030204 cardiovascular system & hematology
Left ventricular hypertrophy
BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Forensic Medicine
0302 clinical medicine
TLR2
Myocytes
Cardiac
TLR4
BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Patofiziologija
Aged
80 and over
General Medicine
Middle Aged
BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Pathophysiology
Myocardial hypertrophy
cardiovascular system
Cardiology
HSP60
Female
Hypertrophy
Left Ventricular
Autopsy
Signal Transduction
Adult
medicine.medical_specialty
animal structures
Mitochondrial Proteins
03 medical and health sciences
Internal medicine
medicine
Humans
overexpression
Aged
business.industry
Myocardium
fungi
BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Sudska medicina
Chaperonin 60
medicine.disease
Toll-Like Receptor 2
Toll-Like Receptor 4
030104 developmental biology
Death
Sudden
Cardiac
Gene Expression Regulation
Case-Control Studies
business
Zdroj: Scandinavian Journal of Clinical and Laboratory Investigation
ISSN: 0036-5513
1502-7686
DOI: 10.1080/00365513.2020.1725977
Popis: 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 60kDa 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 duriing pathogenesis of secondary complications consequently to the left ventricular hypertrophy.
Databáze: OpenAIRE
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