The heart-liver axis controls platelet turnover by hepatic STAT3 phosphorylation and TPO regulation after acute myocardial infarction

Platelets are vital in the clotting process following a heart attack. Their influence on the production of a protein called thrombopoietin (TPO) in the liver after such an event is not yet fully understood. Researchers conducted experiments on mice, both healthy and with specific genetic modifications, to observe the impact of acute myocardial infarction (AMI) on platelet activation, turnover, and hepatic TPO regulation.

The study found that after a heart attack, there was an accelerated platelet production, marked by a higher number of reticulated and desialylated platelets. Concurrently, liver cells (hepatocytes) showed increased expression of certain receptors, such as Asgr1/2 and IL-6R. Additionally, the liver's STAT3 protein showed elevated phosphorylation levels. These changes resulted in higher TPO levels in the bloodstream and a rapid recovery of platelet counts following the heart attack.

However, when platelets were depleted artificially, it triggered a compensatory increase in TPO production by the liver and plasma TPO levels. This response was different in mice lacking the GPVI protein, which is involved in platelet receptor function. These mice did not show major alterations in TPO regulation, indicating that the heart-liver axis plays a unique role in platelet homeostasis after AMI.

These findings reveal a previously unknown connection between the heart and liver in controlling platelet turnover, with hepatic STAT3 signaling serving as a crucial mediator. Understanding this heart-liver axis could lead to new therapeutic strategies for managing platelet homeostasis after a heart attack.