Inhibition of TRIF-Dependent Inflammation Decelerates Afterload-Induced Myocardial Remodeling.

Pressure-overload-induced cardiac hypertrophy represents one cause of the development of heart failure. The aim of this study is to characterize the influence of the TIR-domain-containing adapter-inducing interferon-β (TRIF) during afterload-induced myocardial remodeling. After trans-aortic constriction (TAC), cardiac pressure overload leads to an early increase in MyD88- (Myeloid differentiation primary response gene 88) and TRIF-dependent cytokines.

Pro-oxidative priming but maintained cardiac function in a broad spectrum of murine models of chronic kidney disease.

Aims: Patients with chronic kidney disease (CKD) have an increased risk of cardiovascular events and exhibit myocardial changes including left ventricular (LV) hypertrophy and fibrosis, overall referred to as 'uremic cardiomyopathy'. Although different CKD animal models have been studied for cardiac effects, lack of consistent reporting on cardiac function and pathology complicates clear comparison of these models. Therefore, this study aimed at a systematic and comprehensive comparison of cardiac function and cardiac pathophysiological characteristics in eight different CKD models and mouse strains, with a main focus on adenine-induced CKD.

Photonuclear Alchemy: Obtaining Medical Isotopes of Gold from Mercury Irradiated on Electron Accelerators.

In our work, the photonuclear production of Au isotopes for nuclear medicine purposes was studied, and a method for their recovery from irradiated mercury was developed. The yields of the corresponding nuclear reactions were determined, and a comparison of various methods of obtaining gold radioisotopes was provided. New sorbents based on benzo-15-crown-5, which selectively binds gold, were studied, and the optimal conditions for Au recovery with a high degree of purification from mercury were found.

Renal denervation reduces atrial remodeling in hypertensive rats with metabolic syndrome.

Atrial fibrillation (AF) is highly prevalent in hypertensive patients with metabolic syndrome and is related to inflammation and activation of the sympathoadrenergic system. The multi-ligand Receptor-for-Advanced-Glycation-End-products (RAGE) activates inflammation-associated tissue remodeling and is regulated by the sympathetic nervous system. Its counterpart, soluble RAGE (sRAGE), serves as anti-inflammatory decoy receptor with protective properties.

Recovery of Lu from Irradiated HfO Targets for Nuclear Medicine Purposes.

A new method of production of one of the most widely used isotopes in nuclear medicine, Lu, with high chemical purity was developed; this method includes irradiation of the HfO target with bremsstrahlung photons. The irradiated target was dissolved in HF and then diluted and placed onto a column filled with LN resin. Quantitative sorption of Lu could be observed during this process.

Yields of Photo-Proton Reactions on Nuclei of Nickel and Separation of Cobalt Isotopes from Irradiated Targets.

Nowadays, cobalt isotopes Co, Co, and Co are considered to be promising radionuclides in nuclear medicine, with Co receiving the most attention as an isotope for diagnostics by positron emission tomography. One of the current research directions is dedicated to its production using electron accelerators (via photonuclear method). In our work, the yields of nuclear reactions occurring during the irradiation of Ni and Ni by bremsstrahlung photons with energy up to 55 MeV were determined.

Renal Denervation Prevents Atrial Arrhythmogenic Substrate Development in CKD.

Background: In patients with chronic kidney disease (CKD), atrial fibrillation (AF) is highly prevalent and represents a major risk factor for stroke and death. CKD is associated with atrial proarrhythmic remodeling and activation of the sympathetic nervous system. Whether reduction of the sympathetic nerve activity by renal denervation (RDN) inhibits AF vulnerability in CKD is unknown.

Loss of Mitochondrial Ca Uniporter Limits Inotropic Reserve and Provides Trigger and Substrate for Arrhythmias in Barth Syndrome Cardiomyopathy.

Background: Barth syndrome (BTHS) is caused by mutations of the gene encoding tafazzin, which catalyzes maturation of mitochondrial cardiolipin and often manifests with systolic dysfunction during early infancy. Beyond the first months of life, BTHS cardiomyopathy typically transitions to a phenotype of diastolic dysfunction with preserved ejection fraction, blunted contractile reserve during exercise, and arrhythmic vulnerability. Previous studies traced BTHS cardiomyopathy to mitochondrial formation of reactive oxygen species (ROS).

Prevalence of hemotropic mycoplasmas and coinfection with feline leukemia virus and feline immunodeficiency virus in cats in the Moscow region, Russia.

Feline haemoplasma infection studies are lacking in Russia. This retrospective study was conducted to estimate the prevalence of feline haemoplasmas in domestic cats in the Moscow region, Russia. A risk of haemoplasma coinfection with feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) was also determined.

Carbon Nanomaterials for Sorption of Ga for Potential Using in Positron Emission Tomography.

In present work, carbon nanomaterials (CNMs) are investigated as potential carriers of Ga, which is widely used in positron emission tomography (PET) in nuclear medicine. Sorption behavior of Ga was studied onto CNMs of various structures and chemical compositions: nanodiamonds (ND), reduced graphite oxide (rGiO) and multi-walled carbon nanotubes (MWCNT), as well as their oxidized (ND-COOH) or reduced (rGiO-H, MWCNT-H) forms. The physicochemical properties of the nanoparticles were determined by high resolution transmission electron microscopy, x-ray photoelectron spectroscopy, dynamic light scattering and potentiometric titration.

Raf kinase inhibitor protein mediates myocardial fibrosis under conditions of enhanced myocardial oxidative stress.

Fibrosis is a hallmark of maladaptive cardiac remodelling. Here we report that genome-wide quantitative trait locus (QTL) analyses in recombinant inbred mouse lines of C57BL/6 J and DBA2/J strains identified Raf Kinase Inhibitor Protein (RKIP) as genetic marker of fibrosis progression. C57BL/6 N-RKIP mice demonstrated diminished fibrosis induced by transverse aortic constriction (TAC) or CCl (carbon tetrachloride) treatment compared with wild-type controls.

Sympathoadrenergic suppression improves heart function by upregulating the ratio of sRAGE/RAGE in hypertension with metabolic syndrome.

Receptors-for-Advanced-Glycation-End-products (RAGE) activate pro-inflammatory programs mediated by carboxymethyllysine (CML) and high-mobility-group-box1 protein (HMGB1). The soluble isoform sRAGE neutralizes RAGE-ligands preventing cardiovascular complications in conditions associated with increased sympathetic activation like hypertension and diabetes. The effects of sympathetic modulation on RAGE/sRAGE-balance and end-organ damage in metabolic syndrome on top of hypertension remains unknown.

Cardiopulmonary bypass reduces myocardial oxidative stress, inflammation and increases c-kitCD45 cell population in newborns.

Background: The aim of this study was to characterize the influence of cardiopulmonary bypass (CPB) on myocardial remodeling in newborns and children.

Methods: Biopsies from the right atrium were taken before and after CPB from 4 newborns (5-11 days old) and 7 children (8 months-16 years old). Immunostainings on 10 µm heart tissue frozen sections were performed to detect c-kit cells, leukocytes (CD45 cells), Ki67 cycling cells.

Suppressed MMP-9 Activity in Myocardial Infarction-Related Cardiogenic Shock Implies Diminished Rage Degradation.

Background: Receptor for advanced glycation end products (RAGE) and its cleavage fragment soluble RAGE (sRAGE) are opposite players in inflammation. Enhanced monocytic RAGE expression and decreased plasma sRAGE levels are associated with higher mortality in infarction-related cardiogenic shock. Active matrix metalloproteinase-9 (MMP-9) has been implied in RAGE ectodomain cleavage and subsequently sRAGE shedding in vitro.

Rac1 GTPase regulates 11β hydroxysteroid dehydrogenase type 2 and fibrotic remodeling.

The aim of the study was to characterize the role of Rac1 GTPase for the mineralocorticoid receptor (MR)-mediated pro-fibrotic remodeling. Transgenic mice with cardiac overexpression of constitutively active Rac1 (RacET) develop an age-dependent phenotype with atrial dilatation, fibrosis, and atrial fibrillation. Expression of MR was similar in RacET and WT mice.

C-kit(+) resident cardiac stem cells improve left ventricular fibrosis in pressure overload.

To investigate the effect of resident cardiac stem cells (RCSC) on myocardial remodeling, c-kit(+) RCSC were isolated from hearts of C57Bl/6-Tg (ACTb-EGFP)1Osb/J mice expressing green fluorescent protein and expanded in vitro. C57/Bl6N wildtype mice were subjected to transverse aortic constriction (TAC, 360 μm) or sham-operation. 5 × 10(5) c-kit(+) RCSC or c-kit(-) cardiac cells or cell buffer were infused intravenously 24 h post-surgery (n = 11-24 per group).

Inhibition of endothelial nitric oxide synthase induces and enhances myocardial fibrosis.

Aims: The endothelial nitric oxide synthase (eNOS) contributes to cardiac remodelling. We studied the role of eNOS in the development of myocardial fibrosis during cardiac overload.

Methods And Results: Ten-week-old male C57/Bl6 wildtype (WT) and eNOS mice (eNOS(-/-)) were subjected to transverse aortic constriction (TAC, 360 μm) and WT were treated with L-N(G)-nitroarginine methyl ester (L-NAME, 100 mg/kg/day) for 35 days.

Heart rate reduction by If-inhibition improves vascular stiffness and left ventricular systolic and diastolic function in a mouse model of heart failure with preserved ejection fraction.

Aims: In diabetes mellitus, heart failure with preserved ejection fraction (HFPEF) is a significant comorbidity. No therapy is available that improves cardiovascular outcomes. The aim of this study was to characterize myocardial function and ventricular-arterial coupling in a mouse model of diabetes and to analyse the effect of selective heart rate (HR) reduction by If-inhibition in this HFPEF-model.

Role of receptor for advanced glycation end products in cardiogenic shock.

Objectives: Activation of the receptor for advanced glycation end products by its ligands promotes inflammatory processes and tissue injury. The available evidence suggests that soluble forms of receptor for advanced glycation end products circulating in the plasma may neutralize the ligand-mediated damage by acting as a decoy. Thus, it is hypothesized that receptor for advanced glycation end products expression might be deleterious, whereas soluble receptor for advanced glycation end products might be beneficial in cardiogenic shock.

Ramipril and telmisartan exhibit differential effects in cardiac pressure overload-induced hypertrophy without an additional benefit of the combination of both drugs.

Objectives: We aimed to characterize different cellular effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin 1 (AT1) receptor blockers (ARBs) as mono- or combination therapy in cardiac pressure overload. Methods and

Results: C57B1/6 mice received either the ACEI ramipril (2.5 mg/kg body weight), the ARB telmisartan (20 mg/kg body weight), or the combination.

Endothelial nitric oxide synthase of the bone marrow regulates myocardial hypertrophy, fibrosis, and angiogenesis.

Aims: The endothelial nitric oxide synthase (eNOS) regulates the mobilization and function of endothelial progenitor cells (EPC). We hypothesized that eNOS of the bone marrow (BM) affects cardiac remodelling during myocardial hypertrophy via the regulation of BM-derived vascular progenitor cells.

Methods And Results: Ten-week-old male C57/Bl6 wild-type (WT) and eNOS mice (eNOS(-/-)) were subjected to transverse aortic constriction (TAC, 360 μm, 35 days) or sham operation inducing cardiac hypertrophy and increasing the numbers of Ki67+ cardiomyocytes in both strains.

Ischaemia-induced up-regulation of Toll-like receptor 2 in circulating monocytes in cardiogenic shock.

Aims: To investigate the role of Toll-like receptor 2 (TLR2) in uncomplicated acute myocardial infarction (AMI) and in cardiogenic shock (CS).

Methods And Results: In patients with uncomplicated AMI (n = 20), CS (n = 30) and in age-matched healthy controls (HC; n = 20), TLR2 expression on monocytes was assessed by flow cytometry. Tumour necrosis factor alpha (TNFα) and interleukin-6 (IL6) expression in monocytes was analysed by intracellular cytokine staining.