+1 (629)348-3199Ca2+/Calmodulin-dependent kinase II delta B is essential for Cardiomyocyte Hypertrophy and complement factors gene expression, after TLR-4 stimulation in vitro
Joint Event on 3rd World Congress on Cardiology & 16th International Conference on Nutrition and Fitness
October 29-30, 2018 | London, UK
Marcela Sorelli Carneiro Ramos
Federal University of ABC, Brazil
Scientific Tracks Abstracts : J Nutr Hum Health
Abstract:
Background: The immune system leads to interface between
several other systems and tissues including cardiovascular
system. Cardiac response may be initiated by Toll-like receptors
(TLRs) [pathogen-related molecular (PAMPs) or damagerelated
(DAMPs)], through the complement system (SC) or
by both combined responses. In the inflammatory process,
C3a component of SC is released in large amounts and binds
to the C3aR receptor, which we have already known that is
influenced by the activation of TLRs, inducing the transcription
of inflammatory factors through the translocation of nuclear
transcription factor kappa B (NF-kB) to the nucleus.
Aims: The aim of this study was to evaluate the participation of
the complement system in the development of TLR4-induced
cardiac hypertrophy through CamKIIδ pathway in primary
culture of cardiomyocytes.
Methods: Cells obtained by primary culture of cardiomyocytes
from neonates Wistar rats. There were three main treatments:
control cells untreated, cells treated with TLR4 agonists (HSP60
and LPS) and cells treated with siRNA of CamKIIδ prior to
the TLR4 agonists treatment. Real time PCR were utilized to
analyze gene expression of markers of cardiac hypertrophy,
complement components, inflammatory cytokines and NF-kB.
Results: The mRNA expression of cardiac hypertrophy biomarkers
(BNP and alpha-actin) showed a significantly increase when
cardiomyocytes were treated only with LPS and HSP60 (p<0.05).
It was reverted when the CamKIIδ was silenced. The same
pattern was observed in the complement system components:
C3 and Cfb mRNA expression were increased after TLR4-agonists
treatments however it was attenuated after CamKIIδ silencing
when compared to control groups. Even though the NF-kB
mRNA levels are significantly increase after the LPS and HSP60
treatment, we could observe an attenuation after the CamKIIδ
silencing but it did not revert the expression to similar to control
group (p<0.05). Concerning the inflammatory cytokines (IL-6
and TNF-alpha), they have a significantly increase compared
to control groups (p<0.05), however it did not change with
the siRNA treatment.
Conclusion: We show that stress stimulus induced by HSP60
promotes cardiomyocyte hypertrophy, accompanied by initiation
of inflammatory response via complement system. Whereas
silencing CaMKIIδ is sufficient to prevent the hypertrophic growth
and i it is not to prevent the inflammation. Findings presented
here complement actual understanding on CaMKII mechanisms
behind inflammation mediated cardiomyopathies.
Biography:
Marcela Sorelli Carneiro Ramos is graduated in Biomedicine (2001), completed a PhD (2006) and Post-Doctoral (2008) in the Department of Cell Biology and Development of the Institute of Biomedical Sciences of the University of São Paulo. The research developed in this period, addressed the role of the Renin-Angiotensin System in the thyroid hormone-induced cardiac hypertrophy, as well the effect of thyroxine on global gene expression modulation. Nowadays, the research line aim to study the impact of the inflammatory response and immune system on the cardiovascular changes observed in the Cardiorenal Syndrome. She is an Associate Professor at the Federal University of ABC and has experience in cell and molecular biology, cardiovascular physiology, inflammation and renal failure.
E-mail: marcela.ramos@ufabc.edu.br
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