Combination of ALX and FSK minimized LPS-induced inflammatory response during CCS with much efficacy
The inhibitory effect of ALX on GRK5, which participates in maladaptive activities in cardiac and immune cells, was used to treatment PMɸ challenged with LPS under CCS condition to attenuate the invocation of a hyperactive immune response. FSK was also utilized to directly stimulate ACs to synthesize cAMP, which has a positive effect on chronotropic and inotropic in cardiomyocytes and an anti-inflammatory effect in immune cells to modulate PMɸresponse during CCS. Also, the stressed PMɸ challenged with LPS were also treated with the combination of ALX and FSK.
Results from ELISA analysis of the supernatants from all groups are demonstrated in (Fig. 3). Although all the therapeutic invention groups (ALX, FSK, and ALX with FSK) decreased the extent of immune hyperactivation of PMɸ elicited by LPS during CCS, the single treatment of ALX had the least efficacy compared with FSK single therapy and their combine therapy. More than the single treatment with FSK after the PMɸ had been challenged with LPS under stress, the combination treatment with ALX and FSK was effective in minimizing IL-1β, IL-6, and TNFα (Fig. 3a-3c) secretions while keeping IL-10 upregulated (Fig. 3d).