The polarity protein Scrib limits atherosclerosis development in mice.

Aims: The protein Scrib (Scribble 1) is known to control apico-basal polarity in epithelial cells. The role of polarity proteins in the vascular system remains poorly characterized; however, we previously reported that Scrib maintains the endothelial phenotype and directed migration. On this basis, we hypothesized that Scrib has anti-atherosclerotic functions.

The Histone Demethylase PHF8 Is Essential for Endothelial Cell Migration.

Epigenetic marks critically control gene expression and thus the cellular activity state. The functions of many epigenetic modifiers in the vascular system have not yet been studied. We screened for histone modifiers in endothelial cells and observed a fairly high expression of the histone plant homeodomain finger protein 8 (PHF8).

The NADPH oxidase Nox4 has anti-atherosclerotic functions.

Aims: Oxidative stress is thought to be a risk for cardiovascular disease and NADPH oxidases of the Nox family are important producers of reactive oxygen species. Within the Nox family, the NADPH oxidase Nox4 has a unique position as it is constitutively active and produces H2O2 rather than [Formula: see text] . Nox4 is therefore incapable of scavenging NO and its low constitutive H2O2 production might even be beneficial.

Polarity Protein Scrib Facilitates Endothelial Inflammatory Signaling.

Objective: The polarity protein Scrib is highly expressed in endothelial cells and is required for planar cell polarity. Scrib also facilitates recycling of integrin α5 to the plasma membrane. Because integrin α5 signals the presence of the inflammatory matrix protein fibronectin, we hypothesized that Scrib contributes to endothelial inflammatory signaling.

Nox4 supports proper capillary growth in exercise and retina neo-vascularization.

Key Points: We provide evidence for two distinct functions of the NADPH oxidase Nox4 in angiogenesis using Nox4 knockout mice. First, Nox4 maintains vascular endothelial growth factor expression and prevents an increase in angiopoietin 1 expression, thereby contributing to angiogenesis in exercise. Second, deletion of Nox4, via an enhanced angiopoietin 1 expression, contributes to stabilization of new formed vessels and prevents an exacerbated neo-angiogenesis in oxygen-induced retinopathy.

Vitamin D promotes vascular regeneration.

Background: Vitamin D deficiency in humans is frequent and has been associated with inflammation. The role of the active hormone 1,25-dihydroxycholecalciferol (1,25-dihydroxy-vitamin D3; 1,25-VitD3) in the cardiovascular system is controversial. High doses induce vascular calcification; vitamin D3 deficiency, however, has been linked to cardiovascular disease because the hormone has anti-inflammatory properties.

The polarity protein Scrib is essential for directed endothelial cell migration.

Rationale: Polarity proteins are involved in the apico-basal orientation of epithelial cells, but relatively little is known regarding their function in mesenchymal cells.

Objective: We hypothesized that polarity proteins also contribute to endothelial processes like angiogenesis.

Methods And Results: Screening of endothelial cells revealed high expression of the polarity protein Scribble (Scrib).

Nox4 is a protective reactive oxygen species generating vascular NADPH oxidase.

Rationale: The function of Nox4, a source of vascular H(2)O(2), is unknown. Other Nox proteins were identified as mediators of endothelial dysfunction.

Objective: We determined the function of Nox4 in situations of increased stress induced by ischemia or angiotensin II with global and tamoxifen-inducible Nox4(-/-) mice.