Dysregulation of Nitrosylation Dynamics Promotes Nitrosative Stress and Contributes to Cardiometabolic Heart Failure with Preserved Ejection Fraction.

Background: Recent reports suggest increased myocardial iNOS expression leads to excessive protein -nitrosylation, contributing to the pathophysiology of HFpEF. However, the relationship between NO bioavailability, dynamic regulation of protein -nitrosylation by trans- and de-nitrosylases, and HFpEF pathophysiology has not been elucidated. Here, we provide novel insights into the delicate interplay between NO bioavailability and protein -nitrosylation in HFpEF.

Integrated systems biology identifies disruptions in mitochondrial function and metabolism as key contributors to heart failure with preserved ejection fraction (HFpEF).

Background: Heart failure with preserved ejection fraction (HFpEF) accounts for ~50% of HF cases, with no effective treatments. The ZSF1-obese rat model recapitulates numerous clinical features of HFpEF including hypertension, obesity, metabolic syndrome, exercise intolerance, and LV diastolic dysfunction. Here, we utilized a systems-biology approach to define the early metabolic and transcriptional signatures to gain mechanistic insight into the pathways contributing to HFpEF development.

Reduced Hydrogen Sulfide Bioavailability Contributes to Cardiometabolic Heart Failure with Preserved Ejection Fraction.

Background: Heart failure with preserved ejection fraction (HFpEF) is a significant public health concern with limited treatment options. Dysregulated nitric oxide-mediated signaling has been implicated in HFpEF pathophysiology, however, little is known about the role of endogenous hydrogen sulfide (H2S).

Objectives: This study evaluated H2S bioavailability in patients and two animal models of cardiometabolic HFpEF and assessed the impact of H2S on HFpEF severity through alterations in endogenous H2S production and pharmacological supplementation.

BMI ≥ 70: A Multi-Center Institutional Experience of the Safety and Efficacy of Metabolic and Bariatric Surgery Intervention.

Purpose: With the escalating prevalence of obesity, healthcare providers are increasingly managing patients with a body mass index (BMI) exceeding 70. The aim of this study was to describe the perioperative experiences of this demographic group at two institutions.

Methods: An analysis encompassing 84 patients presenting with BMI ≥ 70 kg/m from two institutions was conducted.

Impact of progressive chronic kidney disease stage on postoperative outcomes in metabolic surgery-a propensity-matched analysis using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement database.

Background: Metabolic surgery (MS) is effective in improving renal parameters for individuals with obesity and chronic kidney disease (CKD). Despite recognized benefits, concerns linger about the perioperative safety of patients with CKD undergoing MS. This study aimed to identify the CKD stage associated with the most significant increase in postoperative complications.

Adjunctive therapy with an oral HS donor provides additional therapeutic benefit beyond SGLT2 inhibition in cardiometabolic heart failure with preserved ejection fraction.

Background And Purpose: Sodium glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a potent therapy for heart failure with preserved ejection fraction (HFpEF). Hydrogen sulphide (HS), a well-studied cardioprotective agent, could be beneficial in HFpEF. SGLT2i monotherapy and combination therapy involving an SGLT2i and HS donor in two preclinical models of cardiometabolic HFpEF was investigated.

Early Renal Denervation Attenuates Cardiac Dysfunction in Heart Failure With Preserved Ejection Fraction.

Background: The renal sympathetic nervous system modulates systemic blood pressure, cardiac performance, and renal function. Pathological increases in renal sympathetic nerve activity contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). We investigated the effects of renal sympathetic denervation performed at early or late stages of HFpEF progression.

Cardiovascular dysfunction induced by combined exposure to nicotine inhalation and high-fat diet.

Smoking and high-fat diet (HFD) consumption are two modifiable risk factors for cardiovascular (CV) diseases, and individuals who are overweight or obese due to unhealthy diet are more likely to use tobacco products. In this study, we aim to investigate the combined effects of nicotine (the addictive component of all tobacco products) and HFD on CV health, which are poorly understood. C57BL/6N male mice were placed on either HFD (60 kcal% fat) or regular diet (22 kcal% fat) and exposed to air or nicotine vapor for 10-12 wk.

Hydrogen Sulfide Modulates Endothelial-Mesenchymal Transition in Heart Failure.

Background: Hydrogen sulfide is a critical endogenous signaling molecule that exerts protective effects in the setting of heart failure. Cystathionine γ-lyase (CSE), 1 of 3 hydrogen-sulfide-producing enzyme, is predominantly localized in the vascular endothelium. The interaction between the endothelial CSE-hydrogen sulfide axis and endothelial-mesenchymal transition, an important pathological process contributing to the formation of fibrosis, has yet to be investigated.

Mitochondrial HS Regulates BCAA Catabolism in Heart Failure.

Background: Hydrogen sulfide (HS) exerts mitochondria-specific actions that include the preservation of oxidative phosphorylation, biogenesis, and ATP synthesis, while inhibiting cell death. 3-MST (3-mercaptopyruvate sulfurtransferase) is a mitochondrial HS-producing enzyme whose functions in the cardiovascular disease are not fully understood. In the current study, we investigated the effects of global 3-MST deficiency in the setting of pressure overload-induced heart failure.

Alpha7 nicotinic acetylcholine receptor mediates chronic nicotine inhalation-induced cardiopulmonary dysfunction.

Cigarette smoking remains the leading modifiable risk factor for cardiopulmonary diseases; however, the effects of nicotine alone on cardiopulmonary function remain largely unknown. Previously, we have shown that chronic nicotine vapor inhalation in mice leads to the development of pulmonary hypertension (PH) with right ventricular (RV) remodeling. The present study aims to further examine the cardiopulmonary effects of nicotine and the role of the α7 nicotinic acetylcholine receptor (α7-nAChR), which is widely expressed in the cardiovascular system.

Elevation of Serum Copper in the New Orleans Bariatric Clinic Population: the Norm or Geographically Localized Findings?

Introduction: Circulating micronutrient levels of both serum copper and zinc have been studied to varying degrees in both the general public and patients having undergone bariatric surgery. According to the 2019 ASMBS clinical guidelines, copper supplementation is recommended for patients undergoing metabolic surgery, especially after Roux-en-Y gastric bypass and duodenal switch. Copper excess has not been previously reported to any significant degree in any population.

Hydrogen Sulfide as a Potential Therapy for Heart Failure-Past, Present, and Future.

Hydrogen sulfide (HS) is an endogenous, gaseous signaling molecule that plays a critical role in cardiac and vascular biology. HS regulates vascular tone and oxidant defenses and exerts cytoprotective effects in the heart and circulation. Recent studies indicate that HS modulates various components of metabolic syndrome, including obesity and glucose metabolism.

Activating Sphingosine-1-phospahte signaling in endothelial cells increases myosin light chain phosphorylation to decrease endothelial permeability thereby inhibiting cancer metastasis.

Targeting the metastatic process to prevent disease dissemination in cancer remains challenging. One step in the metastatic cascade involves cancer cells transiting through the vascular endothelium after inflammation has increased the permeability of this cellular layer. Reducing inflammation-mediated gaps in the vascular endothelium could potentially be used to retard metastasis.

Increased circulating microparticles in streptozotocin-induced diabetes propagate inflammation contributing to microvascular dysfunction.

Key Points: Circulating microparticles (MPs) are elevated in many cardiovascular diseases and have been considered as biomarkers of disease prognosis; however, current knowledge of MP functions has been mainly derived from in vitro studies and their precise impact on vascular inflammation and disease progression remains obscure. Using a diabetic rat model, we identified a >130-fold increase in MPs in plasma of diabetic rats compared to normal rats, the majority of which circulated as aggregates, expressing multiple cell markers and largely externalized phosphatidylserine; vascular images illustrate MP biogenesis and their manifestations in microvessels of diabetic rats. Using combined single microvessel perfusion and systemic cross-transfusion approaches, we delineated how diabetic MPs propagate inflammation in the vasculature and transform normal microvessels into an inflammatory phenotype observed in the microvessels of diabetic rats.

Reduction of Endothelial Nitric Oxide Increases the Adhesiveness of Constitutive Endothelial Membrane ICAM-1 through Src-Mediated Phosphorylation.

Nitric oxide (NO) is a known anti-adhesive molecule that prevents platelet aggregation and leukocyte adhesion to endothelial cells (ECs). The mechanism has been attributed to its role in the regulation of adhesion molecules on leukocytes and the adhesive properties of platelets. Our previous study conducted in rat venules found that reduction of EC basal NO synthesis caused EC ICAM-1-mediated firm adhesion of leukocytes within 10-30 min.

New insights into shear stress-induced endothelial signalling and barrier function: cell-free fluid versus blood flow.

Aims: Fluid shear stress (SS) is known to regulate endothelial cell (EC) function. Most of the studies, however, focused on the effects of cell-free fluid-generated wall SS on ECs. The objective of this study was to investigate how changes in blood flow altered EC signalling and endothelial function directly through wall SS and indirectly through SS effects on red blood cells (RBCs).

Intraspecific Competition Impacts Vibrio fischeri Strain Diversity during Initial Colonization of the Squid Light Organ.

Unlabelled: Animal development and physiology depend on beneficial interactions with microbial symbionts. In many cases, the microbial symbionts are horizontally transmitted among hosts, thereby making the acquisition of these microbes from the environment an important event within the life history of each host. The light organ symbiosis established between the Hawaiian squid Euprymna scolopes and the bioluminescent bacterium Vibrio fischeri is a model system for examining how hosts acquire horizontally transmitted microbial symbionts.