Evidence has indicated that plasma ghrelin was elevated in chronic heart failure (CHF) patients with cachexia. The present report studied whether pathophysiologic increment of endogenous ghrelin levels was existed in the progression of adriamycin (ADR)-induced CHF, then the possible compensatory mechanism by which the changes were induced and the relationship between active ghrelin, cardiac function and energy reserve in heart failure (HF) rats were explored. Cardiac function, high energy phosphates (HEP) content, and ghrelin levels in plasma and myocardium were measured at 4 days, 1, 2 and 3 weeks after the last injection of ADR, after which correlation analysis was performed between these markers in HF rats. Results showed that cardiac function decreased early, then was significantly restored and worsened at 3 weeks accompanied by the decrease of myocardial ATP content. Plasma ghrelin level increased significantly at each time point while myocardial ghrelin level increased transiently, then was restored followed by increased oxidative stress status and apoptosis in the weakening heart. Moreover, correlation analysis indicated that the markers of cardiac function and HEP were positively correlated to the endogenous ghrelin levels at the HF stage. This study indicated that the increase of endogenous ghrelin levels during the progression of the HF induced by ADR represent a compensatory self-protective effect by improving cardiac function and retaining myocardial energy reserve; this may be closely linked to anti-oxidative and anti-apoptosis mechanisms through regulating myocardial mitochondria function by ghrelin; but further investigations are necessary.

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Inflammasomes are one kind of important innate immune defense against viral and bacterial infections. Several inflammasome-forming sensors detect molecular patterns of invading pathogens and then trigger inflammasome activation and/or pyroptosis in infected cells, and viruses employ unique strategies to hijack or subvert inflammasome activation. Infection with herpesviruses induces the activation of diverse inflammasomes, including AIM2 and IFI16 inflammasomes; however, how Kaposi's sarcoma-associated herpesvirus (KSHV) counteracts inflammasome activation largely remains unclear. Here, we reveal that the KSHV ORF37-encoded SOX protein suppresses AIM2 inflammasome activation independent of its viral DNA exonuclease activity and host mRNA turnover. SOX interacts with the AIM2 HIN domain through the C-terminal Motif VII region and disrupts AIM2:dsDNA polymerization and ASC recruitment and oligomerization. The Y443A or F444A mutation of SOX abolishes the inhibition of AIM2 inflammasome without disrupting SOX nuclease activity, and a short SOX peptide is capable of inhibiting AIM2 inflammasome activation; consequently, infection with SOX-null, Y443A, or F444A Bac16 recombinant viruses results in robust inflammasome activation, suppressed lytic replication, and increased pyroptosis in human lymphatic endothelial cells in an AIM2-dependent manner. These results reveal that KSHV SOX suppresses AIM2 inflammasome activation to promote KSHV lytic replication and inhibit pyroptosis, representing a unique mechanism for evasion of inflammasome activation during KSHV lytic cycle.