Tie2 Cre mediated changes in antioxidant activity modulates blood pressure and vascular reactivity: a role for Nrf2.

Background: Excessive oxidative stress is well known to participate in the pathogenesis of hypertension. A major regulator of oxidative stress is the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2). However, the role of Nrf2 in the pathogenesis of hypertension is not completely understood, especially at the endothelial cell level.

Effects of Growth and Development on Aqueous Humor Dynamics in Male Dutch Belted Rabbits.

Purpose: This study reports the changes in aqueous humor dynamics (AHD) and biometric parameters associated with growth and maturation in male Dutch-belted rabbits.

Methods: In this prospective observational study, 20 male Dutch-belted rabbits were studied at 4-weekly intervals starting at 10 weeks through 38 weeks of age. Data collected included intraocular pressure (IOP), aqueous flow, outflow facility by tonography and fluorophotometry (acetazolamide method), episcleral venomanometry, central corneal thickness, corneal diameter, anterior chamber depth, and testicular volume.

Cardiac Injury Regulates Neuroinflammation Through Extracellular Vesicle-Mediated Heart-Brain Crosstalk.

Cognitive impairment is common in heart failure patients, contributing to morbidity and mortality. This impairment may be linked to neuroinflammation in heart failure. However, the primacy of the heart-brain axis remains to be completely understood.

Nrf2-Keap1 in Cardiovascular Disease: Which Is the Cart and Which the Horse?

High levels of oxidant stress in the form of reactive oxidant species are prevalent in the circulation and tissues in various types of cardiovascular disease including heart failure, hypertension, peripheral arterial disease, and stroke. Here we review the role of nuclear factor erythroid 2-related factor 2 (Nrf2), an important and widespread antioxidant and anti-inflammatory transcription factor that may contribute to the pathogenesis and maintenance of cardiovascular diseases. We review studies showing that downregulation of Nrf2 exacerbates heart failure, hypertension, and autonomic function.

Quantitative Proteomics Identifies Novel Nrf2-Mediated Adaptative Signaling Pathways in Skeletal Muscle Following Exercise Training.

Exercise training (ExT) improves skeletal muscle health via multiple adaptative pathways. Nrf2 is a principal antioxidant transcription factor responsible for maintaining intracellular redox homeostasis. In this study, we hypothesized that Nrf2 is essential for adaptative responses to ExT and thus beneficial for muscle.

Extracellular Vesicles Regulate Sympatho-Excitation by Nrf2 in Heart Failure.

Background: Chronic heart failure (CHF) is associated with redox imbalance. Downregulation of Nrf2 (nuclear factor [erythroid-derived 2]-like 2) plays important roles in disrupting myocardial redox homeostasis and mediating sympathetic nerve activity in the setting of CHF. However, it is unclear if circulating extracellular vesicles (EVs) elicit sympathetic excitation in CHF by disrupting central redox homeostasis.

Functional, proteomic and bioinformatic analyses of Nrf2- and Keap1- null skeletal muscle.

Key Points: Nrf2 is a master regulator of endogenous cellular defences, governing the expression of more than 200 cytoprotective proteins, including a panel of antioxidant enzymes. Nrf2 plays an important role in redox haemostasis of skeletal muscle in response to the increased generation of reactive oxygen species during contraction. Employing skeletal muscle-specific transgenic mouse models with unbiased-omic approaches, we uncovered new target proteins, downstream pathways and molecular networks of Nrf2 in skeletal muscle following Nrf2 or Keap1 deletion.

Identification of Cardiac Expression Pattern of Transient Receptor Potential Vanilloid Type 1 (TRPV1) Receptor using a Transgenic Reporter Mouse Model.

Transient receptor potential vanilloid type 1 (TRPV1) channels are structurally related, non-selective cation channels that exhibit a high permeability to calcium. Sensory nerve endings expressing TRPV1 channels play a prominent role in regulating the cardiac sympathetic afferent reflex and contribute to cardiac remodeling and dysfunction in chronic heart failure. However, the precise expression of TRPV1 channels in cardiomyocytes vs.

Curcumin improves exercise performance of mice with coronary artery ligation-induced HFrEF: Nrf2 and antioxidant mechanisms in skeletal muscle.

A hallmark of chronic heart failure (HF) with low ejection fraction (HFrEF) is exercise intolerance. We hypothesized that reduced expression of nuclear factor E2-related factor 2 (Nrf2) in skeletal muscle contributes to impaired exercise performance. We further hypothesized that curcumin, a Nrf2 activator, would preserve or increase exercise capacity in HF.

Prostanoid Receptor Antagonist Effects on Intraocular Pressure, Supported by Ocular Biodisposition Experiments.

Purpose: Since all prostanoid receptors affect intraocular pressure (IOP) and endogenous prostanoids are found in ocular tissues, the pressor effects of prostanoid antagonists were comprehensively evaluated. The absence of effects of most of these antagonists was not entirely anticipated. To ensure no false-negative results, ocular biodisposition studies were conducted.