Trametinib alters contractility of paediatric Noonan syndrome-associated hypertrophic myocardial tissue slices.

Aims: No curative treatment is available for RASopathy-associated childhood-onset hypertrophic cardiomyopathy (RAS-CM). Preclinical data and individual reports suggest a beneficial effect of small molecules targeting the RAS-mitogen-activated protein (MAP) kinase (MAPK) pathway in severely affected RAS-CM patients. The aim of this study was to evaluate the biophysical effects of trametinib, rapamycin and dasatinib on cultivated myocardial tissue slices of a paediatric RAS-CM patient using biomimetic cultivation chambers (BMCCs) and to correlate the findings with clinical data.

Oxidative stress initiates hemodynamic change in CKD-induced heart disease.

Chronic kidney disease (CKD) predisposes to cardiac remodeling and coronary microvascular dysfunction. Studies in swine identified changes in microvascular structure and function, as well as changes in mitochondrial structure and oxidative stress. However, CKD was combined with metabolic derangement, thereby obscuring the contribution of CKD alone.

Retinoic acid modulation guides human-induced pluripotent stem cell differentiation towards left or right ventricle-like cardiomyocytes.

Background: Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) by traditional methods are a mix of atrial and ventricular CMs and many other non-cardiomyocyte cells. Retinoic acid (RA) plays an important role in regulation of the spatiotemporal development of the embryonic heart.

Methods: CMs were derived from hiPSC (hi-PCS-CM) using different concentrations of RA (Control without RA, LRA with 0.

Cardiac dysfunction during exercise in young adults with bronchopulmonary dysplasia.

Background: Worldwide, 1-2% of children are born premature and at risk for developing bronchopulmonary dysplasia (BPD). Preterm-born adults are at risk for early cardiovascular disease. The role of BPD is unclear.

Functional maturation and longitudinal imaging of intraportal neonatal porcine islet grafts in genetically diabetic pigs.

Allogeneic intraportal islet transplantation (ITx) has become an established treatment for patients with poorly controlled type 1 diabetes. However, the loss of viable beta-cell mass after transplantation remains a major challenge. Therefore, noninvasive imaging methods for long-term monitoring of the transplant fate are required.

A tryst of 'blood pressure control- sex- comorbidities': the odyssey of basic public health services in Yunnan in quest for truth.

Background: The Basic Public Health Service (BPHS), a recently announced free healthcare program, aims to combat the most prevalent Noncommunicable Disease-"Hypertension" (HTN)-and its risk factors on a nationwide scale. In China, there is a rife that HTN less impacts women during their lifetime. We, therefore, aimed to evaluate the sex disparity in hypertension patients with comorbidities among south-west Chinese and the contribution of BPHS to address that concern.

Combining renin-angiotensin system blockade and sodium-glucose cotransporter-2 inhibition in experimental diabetes results in synergistic beneficial effects.

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibition exerts cardioprotective and renoprotective effects, often on top of renin-angiotensin system (RAS) blockade. We investigated this in diabetic hypertensive (mREN2)27 rats.

Methods: Rats were made diabetic with streptozotocin and treated with vehicle, the angiotensin receptor blocker valsartan, the SGLT2 inhibitor empagliflozin, or their combination.

The microtubule signature in cardiac disease: etiology, disease stage, and age dependency.

Employing animal models to study heart failure (HF) has become indispensable to discover and test novel therapies, but their translatability remains challenging. Although cytoskeletal alterations are linked to HF, the tubulin signature of common experimental models has been incompletely defined. Here, we assessed the tubulin signature in a large set of human cardiac samples and myocardium of animal models with cardiac remodeling caused by pressure overload, myocardial infarction or a gene defect.

The right ventricle in tetralogy of Fallot: adaptation to sequential loading.

Right ventricular dysfunction is a major determinant of outcome in patients with complex congenital heart disease, as in tetralogy of Fallot. In these patients, right ventricular dysfunction emerges after initial pressure overload and hypoxemia, which is followed by chronic volume overload due to pulmonary regurgitation after corrective surgery. Myocardial adaptation and the transition to right ventricular failure remain poorly understood.

Proteomics- and Metabolomics-Based Analysis of Metabolic Changes in a Swine Model of Pulmonary Hypertension.

Pulmonary vein stenosis (PVS) causes a rare type of pulmonary hypertension (PH) by impacting the flow and pressure within the pulmonary vasculature, resulting in endothelial dysfunction and metabolic changes. A prudent line of treatment in this type of PH would be targeted therapy to relieve the pressure and reverse the flow-related changes. We used a swine model in order to mimic PH after PVS using pulmonary vein banding (PVB) of the lower lobes for 12 weeks to mimic the hemodynamic profile associated with PH and investigated the molecular alterations that provide an impetus for the development of PH.

Can Measuring the 'Dual Anchors of Aorta' Enhance the Success Rate of TAVR?-A Single-Center Experience.

Introduction: Chronic severe aortic regurgitation (AR) has a poor long-term prognosis, especially among old-age patients. Considering their advancing age, the surgical approach of aortic valve replacement may not always be the best alternative modality of treatment in such patients. Therefore, this study's primary goal was to provide an initial summary of the medium- and short-term clinical effectiveness of transcatheter aortic valve replacement (TAVR) guided by accurate multi-detector computed tomography (MDCT) measurements in patients with severe and chronic AR, especially in elderly patients.

The Role of the Kynurenine Pathway in the (Patho) physiology of Maternal Pregnancy and Fetal Outcomes: A Systematic Review.

Introduction: Tryptophan is the precursor of kynurenine pathway (KP) metabolites which regulate immune tolerance, energy metabolism, and vascular tone. Since these processes are important during pregnancy, changes in KP metabolite concentrations may play a role in the pathophysiology of pregnancy complications. We hypothesize that KP metabolites can serve as novel biomarkers and preventive therapeutic targets.

Dawning public health services dogma: An indigenous Southwest Chinese perspective in managing hypertension-with or without the "BPHS"?

Background: To alleviate the rising mortality burden due to hypertension and other non-communicable diseases, a new public health policy initiative in 2009 called the Basic Public Health Services (BPHS). Program was introduced by the Chinese government. The goal of the study is to assess the feasibility and impact of a nationwide health care service-the "BPHS".

Predicting protective gene biomarker of acute coronary syndrome by the circRNA-associated competitive endogenous RNA regulatory network.

The mortality and disability rates of acute coronary syndrome (ACS) are quite high. Circular RNA (circRNA) is a competitive endogenous RNA (ceRNA) that plays an important role in the pathophysiology of ACS. Our goal is to screen circRNA-associated ceRNA networks for biomarker genes that are conducive to the diagnosis or exclusion of ACS, and better understand the pathology of the disease through the analysis of immune cells.

Integrated control of coronary blood flow in exercising swine by adenosine, nitric oxide, and K channels.

The interplay of mechanisms regulating coronary blood flow (CBF) remains incompletely understood. Previous studies in dogs indicated that CBF regulation by K channels, adenosine, and nitric oxide (NO) follows a nonlinear redundancy design and fully accounted for exercise-induced coronary vasodilation. Conversely, in swine, these mechanisms appear to regulate CBF in a linear additive fashion with considerable exercise-induced vasodilation remaining when all three mechanisms are inhibited.

Standardizing submaximal exercise intensities for use of supine push-pull exercise during cardiovascular magnetic resonance.

Background: Cardiovascular magnetic resonance (CMR) imaging during supine exercise at (sub)maximal oxygen consumption (VO ) offers unique diagnostic insights. However, maximal VO is not achievable in the supine position and standardizing submaximal exercise intensities remains challenging. Using heart rate or workload could be a viable option to translate VO -based submaximal exercise intensities.

Exercise and hypoxia unmask pulmonary vascular disease and right ventricular dysfunction in a 10- to 12-week-old swine model of neonatal oxidative injury.

Prematurely born young adults who experienced neonatal oxidative injury (NOI) of the lungs have increased incidence of cardiovascular disease. Here, we investigated the long-term effects of NOI on cardiopulmonary function in piglets at the age of 10-12 weeks. To induce NOI, term-born piglets (1.

Pentoxifylline as a therapeutic option for pre-eclampsia: a study on its placental effects.

Background And Purpose: Recently pentoxifylline, a non-selective phosphodiesterase inhibitor and adenosine receptor antagonist, has attracted much interest for the treatment of the increased vascular resistance and endothelial dysfunction in pre-eclampsia. We therefore investigated the placental transfer, vascular effects and anti-inflammatory actions of pentoxifylline in healthy and pre-eclamptic human placentas.

Experimental Approach: The placental transfer and metabolism of pentoxifylline were studied using ex vivo placenta perfusion experiments.

Kynurenine metabolites predict survival in pulmonary arterial hypertension: A role for IL-6/IL-6Rα.

Activation of the kynurenine pathway (KP) has been reported in patients with pulmonary arterial hypertension (PAH) undergoing PAH therapy. We aimed to determine KP-metabolism in treatment-naïve PAH patients, investigate its prognostic values, evaluate the effect of PAH therapy on KP-metabolites and identify cytokines responsible for altered KP-metabolism. KP-metabolite levels were determined in plasma from PAH patients (median follow-up 42 months) and in rats with monocrotaline- and Sugen/hypoxia-induced PH.

Preparation of Human Myocardial Tissue for Long-Term Cultivation.

Cardiomyocyte cultivation has seen a vast number of developments, ranging from two-dimensional (2D) cell cultivation to iPSC derived organoids. In 2019, an ex vivo way to cultivate myocardial slices obtained from human heart samples was demonstrated, while approaching in vivo condition of myocardial contraction. These samples originate mostly from heart transplantations or left-ventricular assist device placements.

A practical guide to setting up pig models for cardiovascular catheterization, electrophysiological assessment and heart disease research.

Over the past years, the use of large animals has become increasingly interesting in translational research, to bridge the gap between basic research in rodents and targeted therapies in humans. Pigs are highly valued in cardiovascular research because of their anatomical, hemodynamic and electrophysiological features, which closely resemble those of humans. For studying these aspects in swine, cardiac catheterization techniques are essential procedures.

Mechanobiology of Microvascular Function and Structure in Health and Disease: Focus on the Coronary Circulation.

The coronary microvasculature plays a key role in regulating the tight coupling between myocardial perfusion and myocardial oxygen demand across a wide range of cardiac activity. Short-term regulation of coronary blood flow in response to metabolic stimuli is achieved via adjustment of vascular diameter in different segments of the microvasculature in conjunction with mechanical forces eliciting myogenic and flow-mediated vasodilation. In contrast, chronic adjustments in flow regulation also involve microvascular structural modifications, termed remodeling.