Heart Disease and Relaxin: New Actions for an Old Hormone

Devarakonda, Teja; Salloum, Fadi N.

doi:10.1016/j.tem.2018.02.008

Cited by 27 publications

(15 citation statements)

References 78 publications

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“…Activation of APJ receptor by apelin increases cardiac contractility 251 , promotes vasodilation and enhances cardiac output 252 . The peptide hormone relaxin and its receptors exert antifibrosis and cardioprotective roles, and serelaxin (recombinant human relaxin 2) is under development as treatment for acute HF 216 . Blockade of vasopressin V2 receptors prevent myocardial dysfunction and renal injury in experimental HF 253 .…”

Section: Gpcrs In Cardiovascular Regulation and Heart Failurementioning

confidence: 99%

G-Protein–Coupled Receptors in Heart Disease

Wang¹,

Gareri²,

Rockman

2018

Circulation Research

232

184

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G protein-coupled receptors (GPCRs) play a central physiological role in the regulation of cardiac function in both health and disease and thus represents one of the largest class of surface receptors targeted by drugs. Several antagonists of GPCRs, such as β adrenergic receptors and angiotensin II receptors, are now considered standard of therapy for a wide range of cardiovascular disease such as hypertension, coronary artery disease, and heart failure. While the mechanism of action for GPCRs was thought to be largely worked-out in the 1980’s and 90’s, recent discoveries have brought to the fore new and previously unappreciated mechanisms for GPCR activation and subsequent downstream signaling. In this review we focus on GPCRs most relevant to the cardiovascular system and discuss traditional components of GPCR signaling and highlight evolving concepts of such as ligand bias, β-arrestin-mediated signaling, and conformational heterogeneity.

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Section: Gpcrs In Cardiovascular Regulation and Heart Failurementioning

confidence: 99%

G-Protein–Coupled Receptors in Heart Disease

Wang¹,

Gareri²,

Rockman

2018

Circulation Research

232

184

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“…The underlying unifying theme is that these responses locally alter blood flow due to localized challenge such as exercise [2]. This can be contrasted with systemic effects associated with changes in cardiac output or hormonal stimuli as observed for example for the effects of the hormone relaxin during pregnancy [3].…”

Section: Vascular Remodeling and Angiogenesismentioning

confidence: 99%

Perspectives: MRI of angiogenesis

Neeman

2018

Journal of Magnetic Resonance

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Angiogenesis, the expansion of the vascular bed, is an important component in remodeling of tissues and organs. Such remodeling is essential for coping with substantial and sustained increase in the demands for supply of oxygen and nutrients and the timely removal of waste products. The vasculature, and its effectiveness in systemic delivery to all parts of the body, regulates the distribution of immune cells and the delivery of therapeutics as well as the dissemination of disease. Therefore, the vascular bed is possibly one of the key organs involved in homeostasis, in health and disease. The critical role of the vasculature in health, and the accessibility to non invasive probing by MRI, renders MRI as a modality of choice for monitoring the vasculature and its adaption to challenges.

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“…In addition to relaxin-2's role in pregnancy, these cellular responses also regulate the physiology of multiple organs in both sexes, including the liver, kidney, heart, lungs, and blood vessels (3,4). Activation of the pleiotropic effects downstream of RXFP1 can improve cardiac function and decrease fibrosis levels, which has generated interest in using relaxin-2 as a treatment for cardiovascular and fibrotic diseases (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Engineering and characterization of a long half-life relaxin receptor RXFP1 agonist

Erlandson

Wang

Jiang

et al. 2022

Preprint

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Relaxin-2 is a peptide hormone with important roles in human cardiovascular and reproductive biology. Its ability to activate cellular responses such as vasodilation, angiogenesis, and anti-inflammatory and anti-fibrotic effects have led to significant interest in using relaxin-2 as a therapeutic for heart failure and several fibrotic conditions. However, recombinant relaxin-2 has a very short serum half-life, limiting its clinical applications. Here we present protein engineering efforts targeting the relaxin-2 hormone in order to increase its serum half-life, while maintaining its ability to activate the G protein-coupled receptor RXFP1. To achieve this, we optimized a fusion between relaxin-2 and an antibody Fc fragment, generating a version of the hormone with a circulating half-life of up to five days in mice while retaining potent agonist activity at the RXFP1 receptor both in vitro and in vivo.

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Heart Disease and Relaxin: New Actions for an Old Hormone

Cited by 27 publications

References 78 publications

G-Protein–Coupled Receptors in Heart Disease

G-Protein–Coupled Receptors in Heart Disease

Perspectives: MRI of angiogenesis

Engineering and characterization of a long half-life relaxin receptor RXFP1 agonist

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