Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 487, Issue -, Pages 54-58Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2019.01.013
Keywords
Relaxin; Heart failure; Diastolic dysfunction; Vasodilation; RXFP1 receptor; Glucocorticoid receptor; Nitric oxide; Endothelin-1
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Heart Failure with preserved Ejection Fraction (HFpEF), a distinct sub-entity of chronic heart failure characterized by generalized inflammatory non-compliance of the cardio-vascular system, is associated with high mortality and still an unmet medical need. Many novel and promising therapeutic approaches have failed in large studies. This review focuses on basic research, pre-clinical and clinical findings that may account for the potential benefit of relaxin-2 in HFpEF. The peptide combines short-term hemodynamic advantages, such as moderate blood pressure decline and functional endothelin-1 antagonism, with a wealth of protective effects harboring long-term benefits, such as anti-inflammatory, anti-fibrotic, and anti-oxidative actions. These pleiotropic effects are exerted through a complex and intricate signaling cascade involving the relaxin-family peptide receptor-1, the glucocorticoid receptor, the nitric oxide system, and a cell type-dependent variety of down-stream mediators.
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