Reactive oxygen species in tendon injury and repair.

Reactive oxygen species (ROS) are chemical moieties that in physiological concentrations serve as fast-acting signaling molecules important for cellular homeostasis. However, their excess either due to overproduction or inability of the antioxidant system to inactivate them results in oxidative stress, contributing to cellular dysfunction and tissue damage. In tendons, which are hypovascular, hypocellular, and composed predominantly of extracellular matrix (ECM), particularly collagen I, ROS likely play a dual role: regulating cellular processes such as inflammation, proliferation, and ECM remodeling under physiological conditions, while contributing to tendinopathy and impaired healing when dysregulated.

Contribution of hypoxia-inducible factor 1alpha to pathogenesis of sarcomeric hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) caused by autosomal-dominant mutations in genes coding for structural sarcomeric proteins, is the most common inherited heart disease. HCM is associated with myocardial hypertrophy, fibrosis and ventricular dysfunction. Hypoxia-inducible transcription factor-1α (Hif-1α) is the central master regulators of cellular hypoxia response and associated with HCM.

NADPH Oxidases: Redox Regulation of Cell Homeostasis & Disease.

The redox signaling network in mammals has garnered enormous interest and taken on major biological significance in recent years as the scope of NADPH oxidases (NOXs) as regulators of physiological signaling and cellular degeneration has grown exponentially. All NOX subtypes have in common the capacity to generate reactive oxygen species (ROS) superoxide anion (O) and/or hydrogen peroxide (HO). A baseline, normal level of ROS formation supports a wide range of processes under physiological conditions.

MicroRNAs in the Regulation of NADPH Oxidases in Vascular Diabetic and Ischemic Pathologies: A Case for Alternate Inhibitory Strategies?

Since their discovery in the vasculature, different NADPH oxidase (NOX) isoforms have been associated with numerous complex vascular processes such as endothelial dysfunction, vascular inflammation, arterial remodeling, and dyslipidemia. In turn, these often underlie cardiovascular and metabolic pathologies including diabetes mellitus type II, cardiomyopathy, systemic and pulmonary hypertension and atherosclerosis. Increasing attention has been directed toward miRNA involvement in type II diabetes mellitus and its cardiovascular and metabolic co-morbidities in the search for predictive and stratifying biomarkers and therapeutic targets.

Molecular signaling pathways in right ventricular impairment of adult patients after tetralogy of Fallot repair.

Background: Right ventricular impairment (RVI) secondary to altered hemodynamics contributes to morbidity and mortality in adult patients after tetralogy of Fallot (TOF) repair. The goal of this study was to describe signaling pathways contributing to right ventricular (RV) remodeling by analyzing over lifetime alterations of RV gene expression in affected patients.

Methods: RV tissue was collected at the time of cardiac surgery in 13 patients with a diagnosis of TOF.

Forestalling age-impaired angiogenesis and blood flow by targeting NOX: Interplay of NOX1, IL-6, and SASP in propagating cell senescence.

In an aging population, intense interest has shifted toward prolonging health span. Mounting evidence suggests that cellular reactive species are propagators of cell damage, inflammation, and cellular senescence. Thus, such species have emerged as putative provocateurs and targets for senolysis, and a clearer understanding of their molecular origin and regulation is of paramount importance.

NADPH oxidases and HIF1 promote cardiac dysfunction and pulmonary hypertension in response to glucocorticoid excess.

Cardiovascular side effects are frequent problems accompanying systemic glucocorticoid therapy, although the underlying mechanisms are not fully resolved. Reactive oxygen species (ROS) have been shown to promote various cardiovascular diseases although the link between glucocorticoid and ROS signaling has been controversial. As the family of NADPH oxidases has been identified as important source of ROS in the cardiovascular system we investigated the role of NADPH oxidases in response to the synthetic glucocorticoid dexamethasone in the cardiovascular system in vitro and in vivo in mice lacking functional NADPH oxidases due to a mutation in the gene coding for the essential NADPH oxidase subunit p22phox.

Stabilization of p22phox by Hypoxia Promotes Pulmonary Hypertension.

Aims: Hypoxia and reactive oxygen species (ROS) have been shown to play a role in the pathogenesis of pulmonary hypertension (PH), a potentially fatal disorder characterized by pulmonary vascular remodeling, elevated pulmonary arterial pressure, and right ventricular hypertrophy. However, how they are linked in the context of PH is not completely understood. We, therefore, investigated the role of the NADPH oxidase subunit p22phox in the response to hypoxia both in vitro and in vivo.

Folic Acid Promotes Recycling of Tetrahydrobiopterin and Protects Against Hypoxia-Induced Pulmonary Hypertension by Recoupling Endothelial Nitric Oxide Synthase.

Aims: Nitric oxide (NO) derived from endothelial NO synthase (eNOS) has been implicated in the adaptive response to hypoxia. An imbalance between 5,6,7,8-tetrahydrobiopterin (BH4) and 7,8-dihydrobiopterin (BH2) can result in eNOS uncoupling and the generation of superoxide instead of NO. Dihydrofolate reductase (DHFR) can recycle BH2 to BH4, leading to eNOS recoupling.

The β3-integrin binding protein β3-endonexin is a novel negative regulator of hypoxia-inducible factor-1.

Aims: Integrins are multifunctional heterodimeric adhesion receptors that mediate the attachment between a cell and the extracellular matrix or other surrounding cells. In endothelial cells, integrins can modulate cell migration and motility. In particular, β3-integrin is expressed in angiogenic vessels.