Periodic injections of Relaxin 2, its pharmacokinetics and remodeling of rat hearts.

Relaxin-2 (RLX), a critical hormone in pregnancy, has been investigated as a therapy for heart failure. In most studies, the peptide was delivered continuously, subcutaneously for 2 weeks in animals or intravenously for 2-days in human subjects, for stable circulating [RLX]. However, pulsatile hormone levels may better uncover the normal physiology.

Cardiovascular effects of relaxin-2: therapeutic potential and future perspectives.

The hormone relaxin-2 has emerged as a promising player in regulating the physiology of the cardiovascular system. Through binding to the relaxin family peptide receptor 1 (RXFP1), this hormone elicits multiple physiological responses including vasodilation induction, reduction of inflammation and oxidative stress, and angiogenesis stimulation. The role of relaxin-2, or its recombinant human form known as serelaxin, has been investigated in preclinical and clinical studies as a potential therapy for cardiovascular diseases, especially heart failure, whose current therapy is still unoptimized.

Bone status in men with heart failure: results from the Studies Investigating Co-morbidities Aggravating Heart Failure.

Aim: To assess bone status expressed as hip bone mineral density (BMD) in men with heart failure (HF).

Methods And Results: A total of 141 male patients with HF underwent dual energy X-ray absorptiometry to assess their BMD. We analysed markers of bone metabolism.

Custodiol Supplemented with Synthetic Human Relaxin Decreases Ischemia-Reperfusion Injury after Porcine Kidney Transplantation.

Ischemia-reperfusion injury (IRI) is inevitable after kidney transplantation (KT), impairing outcomes. Relaxin-2 (RLX) is a promising insulin-related peptide hormone that protects against renal IRI in rodents, although large animal models are needed before RLX can be tested in a human setting. In this blinded, randomized, and placebo-controlled experimental study kidneys from 19 donor pigs were retrieved after perfusion with Custodiol ± RLX (5 or 20 nmol/L) and underwent static cold storage (SCS) for 24 and 48 h, respectively.

Relationship between GFR, intact PTH, oxidized PTH, non-oxidized PTH as well as FGF23 in patients with CKD.

Fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) are regulators of renal phosphate excretion and vitamin D metabolism. In chronic kidney disease (CKD), circulating FGF23 and PTH concentrations progressively increase as renal function declines. Oxidation of PTH at two methionine residues (positions 8 and 18) causes a loss of function.

Serum Parathyroid Hormone Predicts Mortality in Coronary Angiography Patients with Type 2 Diabetes.

Background: Elevated serum levels of parathyroid hormone (PTH), one of the main regulators of calcium homeostasis and vitamin D metabolism, have been proposed as predictors of mortality. The impact of type 2 diabetes mellitus (T2DM) on the putative association between PTH and mortality has not been investigated thus far.

Aim: The aim of our study was to investigate the impact of T2DM on the power of PTH to predict mortality risk.

Plasma Kynurenine Predicts Severity and Complications of Heart Failure and Associates with Established Biochemical and Clinical Markers of Disease.

Background: Kynurenine, a metabolite of the L-tryptophan pathway, plays a pivotal role in neuro-inflammation, cancer immunology, and cardiovascular inflammation, and has been shown to predict cardiovascular events.

Objectives: It was our objective to increase the body of data regarding the value of kynurenine as a biomarker in chronic heart failure (CHF).

Methods: We investigated the predictive value of plasma kynurenine in a CHF cohort (CHF, n = 114); in a second cohort of defibrillator carriers with CHF (AICD, n = 156), we determined clinical and biochemical determinants of the marker which was measured by enzyme immunoassay.

Relaxin-2 for heart failure with preserved ejection fraction (HFpEF): Rationale for future clinical trials.

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.

Impact of Plasma Kynurenine Level on Functional Capacity and Outcome in Heart Failure - Results From Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF).

Background: Kynurenine is a circulating metabolite from the essential amino acid tryptophan. Accelerated degradation of kynurenine in skeletal muscle has been reported to provide an anti-inflammatory effect. The aim of this study was to investigate the association between blood kynurenine and muscle mass/function in patients with heart failure (HF), in whom diseased muscle mass/function plays a pathophysiological role.

Comparison of a Point-Of-Care Test for High-Sensitivity C-Reactive Protein with an Established Immuno-Nephelometric Method.

Background: High-sensitivity C-reactive protein (hsCRP) is an established marker of cardiovascular risk particularly in primary prevention. For years, it was exclusively measured using automated methods in clinical laboratories, but point-of-care tests (POCT) are urgently needed to simplify and hasten the determination of hsCRP.

Methods: This study compared a novel hsCRP POCT with an established nephelometric method in 104 patients showing a broad spectrum of cardiovascular risk.

Relaxin-2 does not ameliorate nephropathy in an experimental model of type-1 diabetes.

Background/aims: In diabetic nephropathy (DN), the current angiotensin-II-blocking pharmacotherapy is frequently failing. For diabetic cardiomyopathy (DC), there is no specific remedy available. Relaxin-2 (Rlx) - an anti-fibrotic, anti-inflammatory, and vasoprotecting peptide – is a candidate drug for both.

Comparison of a new microbiological assay with a standard high-performance liquid chromatographic method for determination of vitamin B6 in serum.

Background: A high-performance liquid chromatographic (HPLC) assay for vitamin B6 in human serum was compared with a novel microbiological assay (ID-Vit) that uses microtitre plates precoated with a specific microorganism, thus avoiding numerous problems associated with the use of stock cultures utilized by common other microbial assay mit B6.

Methods: Data obtained using HPLC were compared with 1D-Vit results in 170 healthy individuals and in 68 patients with coronary artery disease (CAD, 37 with acute coronary syndrome [ACS], 31 with stable CAD). Regression and Bland-Altman analysis were performed.

Recombinant human relaxin-2: (how) can a pregnancy hormone save lives in acute heart failure?

Acute heart failure (AHF) syndrome, characterized by pulmonary and/or venous congestion owing to increased cardiac filling pressures with or without diminished cardiac output, is still associated with high post-discharge mortality and hospitalization rates. Many novel and promising therapeutic approaches, among them endothelin-1, vasopressin and adenosine antagonists, calcium sensitization, and recombinant B-type natriuretic hormone, have failed in large studies. Likewise, the classic drugs, vasodilators, diuretics, and inotropes, have never been shown to lower mortality.

Myostatin - From the Mighty Mouse to cardiovascular disease and cachexia.

In 1997, McPherron et al. created the so-called Mighty Mouse: owing to the knock-out of a new member of the TGF-β superfamily of peptides, this mouse line was extremely hypermuscular and also characterized by very low body fat. The new peptide, a powerful negative muscle regulator, was named myostatin.