Necrotic cardiomyocytes and LPS elicits similar immunogenic
response during CCS
The immune system is implicated in the exacerbation of cardiac
hypertrophy due to its hyperactive inflammation response to the cDAMPs,
cardiac myosin and troponin released by necrotic cardiomyocytes (Kong P
et al., 2014; Hulsmans M et al., 2016).5, 8 Herein, we
provide evidence that the inflammatory responses elicited by
cardiomyocyte necrosis during CCS are very similar to the immune
response invoked by LPS under the same stress conditions. Profiling of
alterations in the inflammatory markers IL-1β, IL-6, IL-10, TNFα, IFNγ,
and NF-κB was done using RNAs isolated directly from the apical
myocardium for RT-qPCR analysis. Results from the analysis showed the
proinflammatory cytokines IL-1β,
IL-6, TNFα, IFNγ, and NF-κB the prototypic inflammatory pathway were
significantly overexpressed in the PCH mice in comparison to Ctrl and
Vhl mice. Meanwhile, PCH mice had their anti-inflammatory cytokine,
IL-10, significantly downregulated on comparing its expression with Ctrl
and Vhl mice (Fig. 2a). Sera from these mice groups were assessed for
the same inflammatory cytokines with ELISA, and the results obtained
showed similarities in expression trends of both the pro and
anti-inflammatory cytokines on comparing the mRNAs expressions with sera
cytokine concentrations (Fig. 2a and 2b).
To compare the immunogenic response between necrotic cardiomyocyte and
LPS during CCS, PMɸ were challenged with ISO and LPS for
24 h and obtained supernatants were analyzed with ELISA. Intriguing, the
resulted revealed under CCS, LPS invokes a hyperactive inflammatory
response like what was observed in PCH mice that had marked myocyte
necrosis (Fig. 2b). The hyperactive immune response elicited by LPS
under CCS was observed elsewhere as well (Laukova M et al., 2018).