Transient receptor potential melastatin 7 cation channel, magnesium and cell metabolism in vascular health and disease.

Preserving the balance of metabolic processes in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), is crucial for optimal vascular function and integrity. ECs are metabolically active and depend on aerobic glycolysis to efficiently produce energy for their essential functions, which include regulating vascular tone. Impaired EC metabolism is linked to endothelial damage, increased permeability and inflammation.

Pharmacological modulation of transglutaminase 2 in the unilateral ureteral obstruction mouse model.

Background: Transglutaminase 2 (TG2) is a multifunctional enzyme involved in fibrosis by promoting transforming-growth-factor-β1 and crosslinking of extracellular matrix proteins. These functions are dependent on the open conformation, while the closed state of TG2 can induce vasodilation. We explored the putative protective role of TG2 in its closed state on development of renal fibrosis and blood pressure (BP) regulation.

Reactive oxygen species in hypertension.

Hypertension is a leading risk factor for stroke, heart disease and chronic kidney disease. Multiple interacting factors and organ systems increase blood pressure and cause target-organ damage. Among the many molecular elements involved in the development of hypertension are reactive oxygen species (ROS), which influence cellular processes in systems that contribute to blood pressure elevation (such as the cardiovascular, renal, immune and central nervous systems, or the renin-angiotensin-aldosterone system).

Protein disulfide isomerase-mediated transcriptional upregulation of Nox1 contributes to vascular dysfunction in hypertension.

Nox1 signaling is a causal key element in arterial hypertension. Recently, we identified protein disulfide isomerase A1 (PDI) as a novel regulatory protein that regulates Nox1 signaling in VSMCs. Spontaneously hypertensive rats (SHR) have increased levels of PDI in mesenteric resistance arteries compared with Wistar controls; however, its consequences remain unclear.

Endothelial NOX5 Obliterates the Reno-Protective Effect of Nox4 Deletion by Promoting Renal Fibrosis via Activation of EMT and ROS-Sensitive Pathways in Diabetes.

Chronic hyperglycemia induces intrarenal oxidative stress due to the excessive production of reactive oxygen species (ROS), leading to a cascade of events that contribute to the development and progression of diabetic kidney disease (DKD). NOX5, a pro-oxidant NADPH oxidase isoform, has been identified as a significant contributor to renal ROS in humans. Elevated levels of renal ROS contribute to endothelial cell dysfunction and associated inflammation, causing increased endothelial permeability, which can disrupt the renal ecosystem, leading to progressive albuminuria and renal fibrosis in DKD.

Mechanisms of Vascular Inflammation and Potential Therapeutic Targets: A Position Paper From the ESH Working Group on Small Arteries.

Inflammatory responses in small vessels play an important role in the development of cardiovascular diseases, including hypertension, stroke, and small vessel disease. This involves various complex molecular processes including oxidative stress, inflammasome activation, immune-mediated responses, and protein misfolding, which together contribute to microvascular damage. In addition, epigenetic factors, including DNA methylation, histone modifications, and microRNAs influence vascular inflammation and injury.

Knockdown of ANGPTL2 promotes left ventricular systolic dysfunction by upregulation of NOX4 in mice.

Angiopoietin-like 2 (ANGPTL2) is a pro-inflammatory and pro-oxidant circulating protein that predicts and promotes chronic inflammatory diseases such as atherosclerosis in humans. Transgenic murine models demonstrated the deleterious role of ANGPTL2 in vascular diseases, while deletion of ANGPTL2 was protective. The nature of its role in cardiac tissues is, however, less clear.

Socioeconomic deprivation and illness trajectory in the Scottish population after COVID-19 hospitalization.

Background: The associations between deprivation and illness trajectory after hospitalisation for coronavirus disease-19 (COVID-19) are uncertain.

Methods: A prospective, multicentre cohort study was conducted on post-COVID-19 patients, enrolled either in-hospital or shortly post-discharge. Two evaluations were carried out: an initial assessment and a follow-up at 28-60 days post-discharge.

SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis.

Purpose: Disorders/differences of sex development (DSD) result from variants in many different human genes but, frequently, have no detectable molecular cause.

Methods: Detailed clinical and genetic phenotyping was conducted on a family with three children. A Sec31a animal model and functional studies were used to investigate the significance of the findings.

Oxidative Stress and Endoplasmic Reticular Stress Interplay in the Vasculopathy of Hypertension.

Under physiologic conditions, reactive oxygen species (ROS) function as signalling molecules that control cell function. However, in pathologic conditions, increased generation of ROS triggers oxidative stress, which plays a role in vascular changes associated with hypertension, including endothelial dysfunction, vascular reactivity, and arterial remodelling (termed the vasculopathy of hypertension). The major source of ROS in the vascular system is NADPH oxidase (NOX).

Recent Advances in Understanding the Mechanistic Role of Transient Receptor Potential Ion Channels in Patients With Hypertension.

The transient receptor potential (TRP) channel superfamily is a group of nonselective cation channels that function as cellular sensors for a wide range of physical, chemical, and environmental stimuli. According to sequence homology, TRP channels are categorized into 6 subfamilies: TRP canonical, TRP vanilloid, TRP melastatin, TRP ankyrin, TRP mucolipin, and TRP polycystin. They are widely expressed in different cell types and tissues and have essential roles in various physiological and pathological processes by regulating the concentration of ions (Ca, Mg, Na, and K) and influencing intracellular signalling pathways.