Cardiorenal syndrome
Heart failure is a complex clinical syndrome characterized by cardiac function that is insufficient to meet systemic demand. The prevalence of heart failure is rapidly increasing partly due to aging society so that heart failure is now considered as a global pandemic.
In addition to abnormalities intrinsic to the heart, dysfunction in other organs and systemic factors greatly affect the development and consequences of HF. In particular, nearly half of chronic HF (CHF) patients also have chronic kidney disease (CKD), which increases their rate of cardiovascular mortality, suggesting cardiorenal linkage via mechanisms still poorly understood. We found that pressure overload in the heart activates renal collecting duct (CD) epithelial cells via sympathetic nerves. Within the kidneys, activated communication between CD cells, tissue macrophages and endothelial cells leads to secretion of CSF2, which in turn stimulates cardiac-resident Ly6Clo macrophages essential for the myocardial adaptive response to pressure overload. We show that CD-specific deletion of the transcription factor Klf5, renal sympathetic denervation or adrenergic beta2 receptor blockade/deletion disrupts the renal response to cardiac pressure overload. Our results clearly demonstrate that dynamic interplay between the heart, brain and kidneys is necessary for proper adaptation to cardiac stress, and highlight the novel homeostatic functions of tissue macrophages and the sympathetic nervous system.
