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

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.

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Tissue was collected immediately after heart explantations; peripheral blood was collected before induction of anesthesia. Medical records were analyzed ECG, anthropometry, blood tests, medication, echocardiography, and invasive hemodynamic measurements.

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Conclusion: Increased RLN1 levels were accompanied by lower myocardial fibrosis rate, which is a novel finding in our patient population with coronary artery disease 1 June Volume 10 Article Simon et al. 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 transplantation.

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We aimed to evaluate perioperative blood tests, echocardiography, and invasive hemodynamic measurements in comparison with circulating RLN1 levels. We hypothesized that circulating RLN1 levels affect the degree of left and right ventricular myocardial fibrosis and act via the Notch signaling pathway in the failing human myocardium. To underpin our hypothesis, we quantified left and right ventricular myocardial fibrosis and its correlation with circulating RLN1 and investigated gene expression levels of RLN1 and Notch-1 signaling.

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Furthermore, we aimed to compare relaxin levels with echocardiography results and hemodynamic parameters in the context of postoperative vasoplegia syndrome as well.

Relaxin RLN is a polypeptide hormone that was first examined for its potential role in reproduction and pregnancy.

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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. The RLN peptide family consists of seven members and produced by interstitial cells of various organs Dschietzig and Stangl, ; Park et al.

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Further studies reported that cardiac cells are able to produce and secrete RLN and their receptors were identified in the heart Taylor and Clark, ; Hsu et al. This fact has been underpinned by several studies in which RLN1-knock out mice were studied Du et al.

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In these animals, large-scale fibrosis was reported in the lungs, kidneys, and left ventricle of the heart Dschietzig et al. This fibrosis was reversible by administrating exogenous RLN Huang et al. Ischemic heart disease is one of the most important causes of heart failure HF. A key mechanism of HF is cardiac remodeling caused by myocardial fibrosis and cardiomyocyte injury Heusch et al.

There are two types of myocardial fibrosis: interstitial fibrosis and replacement myocardial fibrosis Ambale-Venkatesh and Lima, Myocardial interstitial fibrosis is defined by diffuse, disproportionate accumulation of collagen Gonzalez et al.

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Replacement myocardial fibrosis is the result of post-myocardial infarction necrosis and scar formation. Cardiomyocyte injury activates fibroblasts resulting in collagen turnover and extracellular fiber deposition. Even if these mechanisms are essential in the stabilization and relative function of the injured area, they can cause abnormal stiffening and impaired ventricular function, HF, arrhythmia or even sudden cardiac death Weber et al.

If they had undergone no further treatment for their BPH, they were re-assessed with symptom scores and measurements of flow rate. Results The mean follow-up was

Clinical trials have shown that higher endogenous RLN1 levels are present in patients with HF, but these elevated levels proved to be not enough to compensate the above mentioned pathologic mechanisms Gu et al. RLN produced by cardiac myocytes and interstitial cells has been shown to stimulate myocardial cell growth in neonatal mice.

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Other studies have shown that deficiency of RLN1 gene leads to cardiac fibrosis with ageing Samuel et al. All of our patients were active on heart transplantation waiting list upon recruitment. The Heart and Vascular Center at Semmelweis University runs a detailed database for the Transplantation Biobank, in which full medical history, anthropometry, clinical data, medications, blood tests, echocardiography results, pharmacologic, and device therapy such as pacemaker PMimplantable cardioverter defibrillator ICDcardiac resynchronization therapy CRTand mechanical circulatory support MCS data are available upon retrospective collection.

For this study, end-stage HF patients with ischemic etiology were recruited. For control subjects, healthy volunteers of a cross-sectional voluntary cardiovascular screening program Budakalász Health Examination Survey Kiss et al.

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Blood sampling for all HFrEF patients was performed immediately before induction of the anesthesia for heart transplantation surgery. Blood sampling among healthy controls was performed at random time points on their visit of our epidemiology study.

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Echocardiography was performed by various number of investigators from the Heart and Vascular Center and other cardiology centers. Echocardiography data were obtained from the database of the Transplantation Biobank.

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Given the wide range of referring institutes for a heart transplantation, incomplete echocardiography reports existed, which limits interpretation of advanced imaging such as TDI or speckle tracking.

Frontiers in Physiology www. Relaxin-1 in Myocardial Fibrosis scanned and analyzed at 20× magnification images taken at full resolution with a single image dimension set at 1, × pixels, pixel size is 0. The digital pictures were taken by Zeiss Axio microscope. In order to assess average myocardial fibrosis, two sections were processed from each sample and pictures of five different areas were scanned from each section strictly capturing the right and left upper and lower extremities and the center of each sectionthus altogether 20 independent images per sample were taken.

The quantitative analyzes of the images were ízületi fájdalomcsillapító gyógynövények out with software ImageJ bundled with bit Java 1. Then for each component e.

Invasive hemodynamic measurements were carried out via pulmonary artery catheterization PAC to assess eligibility for heart transplantation within 1 month of referral, and at multiple time points in the perioperative period.

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All patients had PAC and invasive hemodynamic measurements at 24 h follow-up, post-operatively. Biobanking Procedure In the Transplantation Biobank of the Heart and Vascular Center at Semmelweis University, we gather various samples of the patients with end-stage heart disease who undergo heart transplantation at the Heart and Vascular Center at Semmelweis University.

  1. Ezekről tehát előre próbáljon meg minél pontosabban tájékozódni.
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  3. Николь увидела входивших в здание октопауков, один из них был явно ранен.
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These samples include the explanted heart for histology and molecular biology probes, and blood samples. The main steps of the biobanking procedure are the following: first, whole blood is pvr prostate normal range in cc from recipients. Experimental procedure strictly followed product catalog guides.

  • Aneszteziológia és intenzív terápia - edrm.hu
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Experimental pvr prostate normal range in cc strictly followed product catalog guide. To further assess levels of standard and novel cardiac biomarkers, NT-pro-BNP, CA and cholinesterase were measured in our blood laboratory, on site. Both methods are gold standard in the examination of tissue fibrosis, however, they are not specific for interstitial myocardial fibrosis. Tissue was fixed for 24 h, room temperature. Later on, ventricular samples were dehydrated in ethanol baths, embedded in paraffin, and mounted on salinized plates.

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For the washing, 0. The stained sections were Frontiers in Physiology www. All subjects gave written informed consent in keeping with the Declaration of Helsinki. Statistical Analyses Samples from 47 independent patients and 36 age and sex matched healthy volunteers were used.

Relaxin-1 in Myocardial Fibrosis experiments were performed with at least three technical replicates.

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