S-Methyl Cysteine Sulfoxide Does Not Ameliorate Weight Gain or Hyperlipidemia in Mice Fed a High-Fat Diet.

Scope: Higher intake of cruciferous and allium vegetables is associated with lower cardiometabolic risk. Little research has investigated the cardiometabolic effects of S-methyl cysteine sulfoxide (SMCSO), found abundant in these vegetables. This study hypothesizes that SMCSO will blunt development of metabolic syndrome features in mice fed high-fat feed.

Comparing and Contrasting the Effects of the SGLT Inhibitors Canagliflozin and Empagliflozin on the Progression of Retinopathy.

Background: Diabetic retinopathy (DR) is a leading cause of end-stage blindness globally and is arguably one of the most disabling complications of both Type 1 and Type 2 diabetes. Sodium Glucose Cotransporter-2 (SGLT2) inhibitors have now been successfully introduced to clinical medicine and exert multiple beneficial effects in diabetic patients. Given the broad therapeutic application of SGLT2 inhibitors, we hypothesised that SGLT2 inhibition may alleviate the progression of DR.

Multi-organ denervation: a novel approach to combat cardiometabolic disease.

Cardiometabolic disorders are associated with a substantial loss in quality of life and pose a large burden on healthcare systems worldwide. Overactivation of the sympathetic nervous system has been shown to be a key player in several aspects relating to cardiometabolic disturbances. While diet- and exercise-induced approaches to help reduce weight remains the main strategy to combat metabolic disorders, this is often difficult to achieve.

Evaluation of Circulating Platelet Extracellular Vesicles and Hypertension Mediated Organ Damage.

Elevated circulating platelet-derived extracellular vesicles (pEVs) have been associated with arterial hypertension. The role of hypertension-mediated organ damage (HMOD) to induce EV release is still unknown. We studied the micro- and macro-vascular changes (retinal vascular density and pulse wave velocity), endothelial function (flow-mediated vasodilation of brachial artery and finger plethysmography), and assessed the psychosocial status (anxiety and depression) in hypertensive patients to determine their relationship with EV release.

Association of Circulating Platelet Extracellular Vesicles and Pulse Wave Velocity with Cardiovascular Risk Estimation.

Elevated circulating platelet-derived extracellular vesicles (EVs) have been reported in conditions associated with thrombotic risk. The present study aimed to assess the relationship between circulating platelet-derived EV levels, cardiovascular risk stratification and vascular organ damage, as assessed by pulse wave velocity (PWV). A total of 92 patients were included in the present analysis.

Platelet-derived extracellular vesicles correlate with therapy-induced nocturnal blood pressure changes.

Introduction: Elevated nocturnal blood pressure (BP) is closely associated with increased risk of cardiovascular (CV) events. Circulating extracellular vesicles (EVs) have been proposed as a potential CV risk biomarker and shown to correlate with BP. The present study aimed to assess whether a reduction in BP is paralleled by respective changes in EVs.

Circulating platelet-derived extracellular vesicles correlate with night-time blood pressure and vascular organ damage and may represent an integrative biomarker of vascular health.

Elevated office blood pressure (BP) has previously been associated with increased levels of circulating extracellular vesicles (EVs). The present study aimed to assess the relationship between levels of platelet derived EVs, ambulatory BP parameters, and pulse wave velocity as a marker of macrovascular organ damage. A total of 96 participants were included in the study.

Retinal Capillary Damage Is Already Evident in Patients With Hypertension and Prediabetes and Associated With HbA1c Levels in the Nondiabetic Range.

Objective: We analyzed whether any change in capillary density in the retinal circulation could be detected in patients with hypertension in the prediabetic stage.

Research Design And Methods: In a cross-sectional analysis, we assessed capillary density in the foveal (CDF) and parafoveal retinal areas using optical coherence tomography-angiography in 62 patients with hypertension and normal glucose metabolism and 40 patients with hypertension and prediabetes.

Results: The CDF was lower in patients with prediabetes than in those with normal glucose metabolism.

The Effect of SGLT2 Inhibition on Diabetic Kidney Disease in a Model of Diabetic Retinopathy.

Diabetic kidney disease (DKD) is a chronic disorder characterized by elevated urine albumin excretion, reduced glomerular filtration rate, or both. At present, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are the standard care for the treatment of DKD, resulting in improved outcomes. However, alternative treatments may be required because although the standard treatments have been found to slow the progression of DKD, they have not been found to halt the disease.

Targeting Features of the Metabolic Syndrome Through Sympatholytic Effects of SGLT2 Inhibition.

Purpose Of Review: The moderate glucose-lowering effect of sodium glucose co-transporter 2 (SGLT2) inhibitors is unlikely to explain SGLT2 inhibitor-mediated beneficial outcomes, and unravelling the underlying mechanisms is a high priority in the research community. Given the dominant pathophysiologic role of the sympathetic nervous system activation in conditions such as hypertension and perturbed glucose homeostasis, it is pertinent to postulate that SGLT2 inhibitors may exert their beneficial effects at least in part via sympathetic inhibition.

Recent Findings: SGLT2 inhibitors have shown enormous potential to improve cardiovascular outcomes in patients with type 2 diabetes, and their therapeutic potential is currently being investigated in a range of associated comorbidities such as heart failure and chronic kidney disease.

Determining the role of SGLT2 inhibition with Empagliflozin in the development of diabetic retinopathy.

Diabetes mellitus is a chronic metabolic disease that occurs when the pancreas is not producing enough insulin or when the insulin that it does produce is not able to be used effectively in the body. This results in hyperglycemia and if the blood sugars are not controlled, then it can lead to serious damage of various body systems, especially the nerves and the blood vessels. Uncontrolled diabetes is a major cause of kidney failure, heart attacks, stroke and amputation.

Interaction between sodium-glucose co-transporter 2 and the sympathetic nervous system.

Purpose Of Review: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have taken centre stage in research and therapeutic efforts to modulate hard clinical outcomes in patients with heightened cardiovascular and renal risk profiles. Sympathetic nervous system (SNS) activation is a prominent feature across several cardiovascular and renal disease states. This review reflects on the remarkable clinical impact of SGLT2 inhibitors on cardiorenal outcomes, and navigates the evidence for a proposed clinically relevant interaction between SGLT2 and the SNS.

A standarized protocol for evaluation of large extracellular vesicles using the attune™ NXT system.

Extracellular vesicles (EVs) represent a promising biomarker in several medical areas. Flow cytometry (FC) is one of the most widely-used methods to characterize EVs, providing quantitative information and determination of EV subtypes. EV evaluation represents a challenge as no standardized methods are available to facilitate assessment across different research centers.

TNFSF14-Derived Molecules as a Novel Treatment for Obesity and Type 2 Diabetes.

Obesity is one of the most prevalent metabolic diseases in the Western world and correlates directly with glucose intolerance and insulin resistance, often culminating in Type 2 Diabetes (T2D). Importantly, our team has recently shown that the TNF superfamily (TNFSF) member protein, TNFSF14, has been reported to protect against high fat diet induced obesity and pre-diabetes. We hypothesized that mimics of TNFSF14 may therefore be valuable as anti-diabetic agents.

Role of Microparticles in Cardiovascular Disease: Implications for Endothelial Dysfunction, Thrombosis, and Inflammation.

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Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)-A Condition Associated with Heightened Sympathetic Activation.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common liver disease affecting a quarter of the global population and is often associated with adverse health outcomes. The increasing prevalence of MAFLD occurs in parallel to that of metabolic syndrome (MetS), which in fact plays a major role in driving the perturbations of cardiometabolic homeostasis. However, the mechanisms underpinning the pathogenesis of MAFLD are incompletely understood.

Metabolic dysfunction induced by a high-fat diet modulates hematopoietic stem and myeloid progenitor cells in brown adipose tissue of mice.

Brown adipose tissue (BAT) may be an important metabolic regulator of whole-body glucose. While important roles have been ascribed to macrophages in regulating metabolic functions in BAT, little is known of the roles of other immune cells subsets, particularly dendritic cells (DCs). Eating a high-fat diet may compromise the development of hematopoietic stem and progenitor cells (HSPCs)-which give rise to DCs-in bone marrow, with less known of its effects in BAT.

Role of the sympathetic nervous system in cardiometabolic control: implications for targeted multiorgan neuromodulation approaches.

Sympathetic overdrive plays a key role in the perturbation of cardiometabolic homeostasis. Diet-induced and exercise-induced weight loss remains a key strategy to combat metabolic disorders, but is often difficult to achieve. Current pharmacological approaches result in variable responses in different patient cohorts and long-term efficacy may be limited by medication intolerance and nonadherence.

Combined renal and common hepatic artery denervation as a novel approach to reduce cardiometabolic risk: technical approach, feasibility and safety in a pre-clinical model.

Background: Cardiovascular and metabolic regulation is governed by neurohumoral signalling in relevant organs such as kidney, liver, pancreas, duodenum, adipose tissue, and skeletal muscle. Combined targeting of relevant neural outflows may provide a unique therapeutic opportunity for cardiometabolic disease.

Objectives: We aimed to investigate the feasibility, safety, and performance of a novel device-based approach for multi-organ denervation in a swine model over 30 and 90 days of follow-up.

Increased pulse wave velocity in patients with an orthostatic blood pressure rise independent of other cardiovascular risk factors.

Background: Positional changes in blood pressure (BP) have been shown to have effects on long-term outcomes. Although a BP drop with upright posture is frequently observed, an orthostatic rise in BP can also occur. Here, we aimed to investigate whether the phenotype of orthostatic hypertension is associated with more pronounced vascular hypertension-mediated organ damage (HMOD) and whether this is associated with other cardiovascular risk factors.