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).