The heart and the liver are in close relation to each other. Impairment of cardiac function may leadtohepatic dysfunction and vice versa (Central Illustration). Liver hypoperfusion and hepatic congestionarethe 2 central pathophysiological mechanisms, both in acute cardiogenic liver injury and hepatic congestion. Cirrhotic cardiomyopathy is a syndrome that includes systolic, diastolic, and electrophysiological abnormalities that develop in the setting of liver cirrhosis. Altered LXR signaling contributes to the development of HF comorbidities. Because the liver is the first organ exposed to the gut toxic molecules produced in HF, gut–liver interaction in the setting of HF has been an exciting new research field. Management of deranged cardiohepatic interactions remains challenging.
Cardiac and Liver Dysfunction Often Co-ExistCo-existence is the result of systemic disorders and diseases affecting both organs (e.g., alcohol abuse, drugs, inflammation, autoimmunity, infections) as well as complex cardiohepatic interactions. The latter interactions include development of acute cardiogenic liver injury and congestive hepatopathy in HF as well as cardiac dysfunction and HF in the setting of liver cirrhosis (cirrhotic cardiomyopathy), nonalcoholic fatty liver disease, and sequelae following liver transplantation. Finally, altered LXR signaling may contribute to the pathogenesis of HF co-morbidities. HF = heart failure; LXR = liver X receptor.
Schematic Relating LXR Signaling to HF Development
In the cell nucleus, LXR form an obligate heterodimer complex with the RXR that binds to regulatory regions of target genes. Following ligand binding, the LXR/RXR complex undergoes a conformational change that leads to the release of co-repressors and recruitment of co-activators, which modulates target gene expression. Altered LXR/RXR signaling contributes to development of HF risk factors and co-morbidities and, consequently, HF. HF = heart failure; LXR = liver X receptor; RXR = retinoid X receptor.
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