Relaxin: a pregnancy hormone as central player of body fluid and circulation homeostasis

Dschietzig, Thomas; Stangl, Karl

doi:10.1007/s00018-003-2169-x

Cited by 34 publications

(4 citation statements)

References 174 publications

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“…46 Interestingly, increased production of relaxin, a hormone secreted by the corpus luteum to relax the pelvic ligaments and a potent vasodilator, may contribute to the increased venous pressures in the lower extremities. 47,48 A recent study published in Circulation used a machine learning approach and confirmed many of the known risk factors but also identified several new strong predictors, including leg bioimpedance and height. 6 Height had been identified as a potential risk factor in an early epidemiological study several decades ago 50 but had been inconsistently reported since.…”

Section: Venous Disease Epidemiologymentioning

confidence: 97%

Epidemiology and Genetics of Venous Thromboembolism and Chronic Venous Disease

Baylis

Smith

Klarin

et al. 2021

Circulation Research

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Venous disease is a term that broadly covers both venous thromboembolic disease and chronic venous disease. The basic pathophysiology of venous thromboembolism and chronic venous disease differ as venous thromboembolism results from an imbalance of hemostasis and thrombosis while chronic venous disease occurs in the setting of tissue damage because of prolonged venous hypertension. Both diseases are common and account for significant mortality and morbidity, respectively, and collectively make up a large health care burden. Despite both diseases having well-characterized environmental components, it has been known for decades that family history is an important risk factor, implicating a genetic element to a patient’s risk. Our understanding of the pathogenesis of these diseases has greatly benefited from an expansion of population genetic studies from pioneering familial studies to large genome-wide association studies; we now have multiple risk loci for each venous disease. In this review, we will highlight the current state of knowledge on the epidemiology and genetics of venous thromboembolism and chronic venous disease and directions for future research.

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Section: Venous Disease Epidemiologymentioning

confidence: 97%

Epidemiology and Genetics of Venous Thromboembolism and Chronic Venous Disease

Baylis

Smith

Klarin

et al. 2021

Circulation Research

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“…Serelaxin (RLX; synonyms: recombinant human relaxin, rhRLX) designates the pharmaceutical form of the human natural hormone relaxin-2 (RLX-2; H2 RLX) suitable for clinical use. In recent years, robust evidence has been accumulating that RLX can markedly reduce tissue and cell damage induced by ischemia and reperfusion (IR) [ 1 , 2 , 3 ]. Such a protective effect has been consistently observed in diverse experimental models, spanning from organ IR in whole animals (heart, gut, kidney) [ 4 , 5 , 6 , 7 , 8 ] and in isolated and perfused organs (heart, lung, liver) [ 9 , 10 , 11 , 12 ] to specific cell types (cardiomyocytes, trophoblast) subjected to in vitro hypoxia (associated or not with nutrient starvation) and reoxygenation [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Human Relaxin-2 (Serelaxin) Attenuates Oxidative Stress in Cardiac Muscle Cells Exposed In Vitro to Hypoxia–Reoxygenation. Evidence for the Involvement of Reduced Glutathione Up-Regulation

et al. 2020

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Serelaxin (RLX) designates the pharmaceutical form of the human natural hormone relaxin-2 that has been shown to markedly reduce tissue and cell damage induced by hypoxia and reoxygenation (HR). The evidence that RLX exerts similar protective effects on different organs and cells at relatively low, nanomolar concentrations suggests that it specifically targets a common pathogenic mechanism of HR-induced damage, namely oxidative stress. In this study we offer experimental evidence that RLX (17 nmol L-1), added to the medium of HR-exposed H9c2 rat cardiac muscle cells, significantly reduces cell oxidative damage, mitochondrial dysfunction and apoptosis. These effects appear to rely on the up-regulation of the cellular availability of reduced glutathione (GSH), a ubiquitous endogenous antioxidant metabolite. Conversely, superoxide dismutase activity was not influenced by RLX, which, however, was not endowed with chemical antioxidant properties. Taken together, these findings verify the major pharmacological role of RLX in the protection against HR-induced oxidative stress, and shed first light on its mechanisms of action.

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“…RLN1 and 2 were reported to increase the collagen solubility in the cervix of the uterine, as well as to soften the pubic symphysis in the pregnant women (Hansell et al, 1991; Sherwood, 2004; Schwabe and Bullesbach, 2007). The RLN peptide family consists of seven members and produced by interstitial cells of various organs (Dschietzig and Stangl, 2003; Park et al, 2005; Kong et al, 2010). Further studies reported that cardiac cells are able to produce and secrete RLN and their receptors were identified in the heart (Taylor and Clark, 1994; Hsu et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Circulating Relaxin-1 Level Is a Surrogate Marker of Myocardial Fibrosis in HFrEF

et al. 2019

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Introduction: Relaxin-1 (RLN1) has emerged as a possible therapeutic target in myocardial fibrosis due to its anti-fibrotic effects. Previous randomized clinical trials investigated therapeutic role of exogenous relaxin in patients with acute-on-chronic heart failure (HF) and failed to meet clinical endpoints. Here, we aimed to assess endogenous, circulating RLN1 levels in patients with heart failure with reduced ejection fraction (HFrEF) of ischemic origin. Furthermore, we analyzed relation of RLN1 and left ventricular diastolic function, left and right ventricular fibrosis, and invasive hemodynamic measurements. Unique feature of our study is the availability of ex vivo human myocardial tissue. Methods: Human myocardial samples were available from the Transplantation Biobank of the Heart and Vascular Center at Semmelweis University after local ethical approval and informed consent of all participants ( n = 47). Tissue was collected immediately after heart explantations; peripheral blood was collected before induction of anesthesia. Myocardial sections were stained for Masson’s trichrome and Picrosirius red staining to quantify fibrosis. Medical records were analyzed (ECG, anthropometry, blood tests, medication, echocardiography, and invasive hemodynamic measurements). Results: Average RLN1 levels in HFrEF population were significantly higher than measured in age and gender matched healthy control human subjects (702 ± 283 pg/ml in HFrEF vs. 44 ± 27 pg/ml in control n = 47). We found a moderate inverse correlation between RLN1 levels and degree of myocardial fibrosis in both ventricles ( r = −0.357, p = 0.014 in the right ventricle vs. r = −0.321, p = 0.028 in the left ventricle with Masson’s trichrome staining). Parallel, a moderate positive correlation was found in left ventricular diastolic function (echocardiography, E/A wave values) and RLN1 levels ( r = 0.456, p = 0.003); a negative correlation with RLN1 levels and left ventricular end-systolic diameter ( r = −0.373, p = 0.023), and diastolic pulmonary artery pressure ( r = −0.894, p < 0.001). RLN1 levels showed moderate correlation with RLN2 levels ( r = 0.453, p = 0.0003). Conclusion: Increased RLN1 levels were accompanied by lower myocardial fibrosis rate, which is a novel finding in our patient population with coronary artery disease and HFrEF. RLN1 can have a biomarker role in ventricular fibrosis; furthermore, it may influence hemodynamic and vasomotor activity via neurohormonal mechanisms of action. Given these valuable findings, RLN1 may be targeted in anti-fibrotic therapeutics and in perioperative care of heart transpl...

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Relaxin: a pregnancy hormone as central player of body fluid and circulation homeostasis

Cited by 34 publications

References 174 publications

Epidemiology and Genetics of Venous Thromboembolism and Chronic Venous Disease

Epidemiology and Genetics of Venous Thromboembolism and Chronic Venous Disease

Human Relaxin-2 (Serelaxin) Attenuates Oxidative Stress in Cardiac Muscle Cells Exposed In Vitro to Hypoxia–Reoxygenation. Evidence for the Involvement of Reduced Glutathione Up-Regulation

Circulating Relaxin-1 Level Is a Surrogate Marker of Myocardial Fibrosis in HFrEF

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