Connecting vascular inflammation and endothelial dysfunction in the cardio-renal axis

Abstract

Chronic heart failure with gradual stiffening of the heart without a preceding myocardial infarction is more often diagnosed in woman with kidney failure compared to males. Current diagnostic tools and available therapies are often not sufficient in this patient population. Improved diagnostics and treatment for this heart failure patients is only possible after thorough understanding of the disease and its underlying pathophysiological mechanism. We highlight the effects of renal dysfunction and vascular inflammation on the development and progression of chronic heart failure. We have addressed possible mechanisms regarding endothelial dysfunction and thereby stiffening (fibrosis) of the small cardiac vasculature in females and suggest inflammatory protein GDF15 as potential new diagnostic or therapeutic target.

In animal related research we have established the contribution of vascular dysfunction to the sex-specific cardiac remodeling within chronic non-ischemic heart failure. Though, high GDF15 levels are related to worse prognosis of heart failure, the lack of GDF15 in animals resulted in adverse cardiac remodeling and increased stiffening of the microvasculature. Future research will elucidate the specific contribution of microvascular stiffening in adverse cardiac remodeling and the possibility of GDF15 to become a specific biomarker or possible novel therapeutic target for chronic heart failure.