Abstract
The endocrine system is crucial for maintaining whole-body homeostasis. Little is known regarding endocrine hormones secreted by the heart other than ANP and BNP discovered over 30 years ago. We recently identified growth differentiation factor 15 (GDF15) as a heart-derived hormone that regulates body growth. Pediatric heart disease induces GDF15 synthesis and secretion by cardiomyocytes. Circulating GDF15 in turn acts on the liver to inhibit growth hormone (GH) signaling and body growth. Blocking cardiomyocyte production of GDF15 normalizes circulating GDF15 level and restores liver GH signaling, establishing GDF15 as a bona fide heart-derived hormone that regulates pediatric body growth. Importantly, plasma GDF15 is further increased in children with concomitant heart disease and failure to thrive. In addition, we used massively parallel single-nucleus RNA-Seq to decipher cardiac cell type specific gene regulatory network that induces GDF15 transcription in heart disease condition. We further determined how GDF15 precursor is processed into mature hormone. Together these studies reveal a new endocrine mechanism (cardiac endocrinology) by which the heart coordinates cardiac function and body growth.
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