Ca2+/Calmodulin-dependent kinase II delta B is essential for cardiomyocyte hypertrophy and complement gene expression after LPS and HSP60 stimulation in vitro

• Published in: Brazilian journal of medical and biological research 2019-01, Vol.52 (7), p.e8732-e8732
• Main Authors: Cruz Junho, C V, Trentin-Sonoda, M, Alvim, J M, Gaisler-Silva, F, Carneiro-Ramos, M S
• Format: Article
• Language: English
• Subjects: BIOLOGY; Calcium-binding protein; Calmodulin; CaMKII; Cardiomyocytes; Cardiovascular diseases; Complement; Complement activation; Complement component C3; Complement factor B; Gene expression; Heat shock proteins; Hsp60 protein; Hypertrophy; Immune system; Inflammation; Interleukin 6; Kinases; Lipopolysaccharides; MEDICINE, RESEARCH & EXPERIMENTAL; NF-κB protein; siRNA; Therapeutic applications; TLR 2/4; Toll-like receptors; Transcription
• ISSN: 0100-879X; 1414-431X; 1414-431X; 1678-4510
• DOI: 10.1590/1414-431X20198732

Inflammation plays an important role in the development of cardiovascular diseases (CVDs), suggesting that the immune system is a target of therapeutic interventions used for treating CVDs. This study evaluated mechanisms underlying inflammatory response and cardiomyocyte hypertrophy associated with bacterial lipopolysaccharide (LPS)- or heat shock protein 60 (HSP60)-induced Toll-like receptor (TLR) stimulation and the effect of a small interfering RNA (siRNA) against Ca2+/calmodulin-dependent kinase II delta B (CaMKIIδB) on these outcomes. Our results showed that treatment with HSP60 or LPS (TLR agonists) induced cardiomyocyte hypertrophy and complement system C3 and factor B gene expression. In vitro silencing of CaMKIIδB prevented complement gene transcription and cardiomyocyte hypertrophy associated with TLR 2/4 activation but did not prevent the increase in interleukin-6 and tumor necrosis factor-alfa gene expression in primary cultured cardiomyocytes. Moreover, CaMKIIδB silencing attenuated nuclear factor-kappa B expression. These findings supported the hypothesis that CaMKIIδB acts as a link between inflammation and cardiac hypertrophy. Furthermore, the present study is the first to show that extracellular HSP60 activated complement gene expression through CaMKIIδB. Our results indicated that a stress stimulus induced by LPS or HSP60 treatment promoted cardiomyocyte hypertrophy and initiated an inflammatory response through the complement system. However, CaMKIIδB silencing prevented the cardiomyocyte hypertrophy independent of inflammatory response induced by LPS or HSP60 treatment.