Estradiol regulates human QT-interval: acceleration of cardiac repolarization by enhanced KCNH2 membrane trafficking.

Background: Modulation of cardiac repolarization by sexual hormones is controversial and hormonal effects on ion channels remain largely unknown. In the present translational study, we therefore assessed the relationship between QTc duration and gonadal hormones and studied underlying mechanisms.

Methods And Results: We measured hormone levels and QTc intervals in women during clomiphene stimulation for infertility and women before, during, and after pregnancy.

Elevated heart rate triggers action potential alternans and sudden death. translational study of a homozygous KCNH2 mutation.

Background: Long QT syndrome (LQTS) leads to arrhythmic events and increased risk for sudden cardiac death (SCD). Homozygous KCNH2 mutations underlying LQTS-2 have previously been termed "human HERG knockout" and typically express severe phenotypes. We studied genotype-phenotype correlations of an LQTS type 2 mutation identified in the homozygous index patient from a consanguineous Turkish family after his brother died suddenly during febrile illness.

N-terminal arginines modulate plasma-membrane localization of Kv7.1/KCNE1 channel complexes.

Background And Objective: The slow delayed rectifier current (I(Ks)) is important for cardiac action potential termination. The underlying channel is composed of Kv7.1 α-subunits and KCNE1 β-subunits.

The Nox family of NADPH oxidases: friend or foe of the vascular system?

NADPH (nicotinamide adenine dinucleotide phosphate) oxidases are important sources of reactive oxygen species (ROS). In the vascular system, ROS can have both beneficial and detrimental effects. Under physiologic conditions, ROS are involved in signaling pathways that regulate vascular tone as well as cellular processes like proliferation, migration and differentiation.

The E-loop is involved in hydrogen peroxide formation by the NADPH oxidase Nox4.

In contrast to the NADPH oxidases Nox1 and Nox2, which generate superoxide (O(2)(·-)), Nox4 produces hydrogen peroxide (H(2)O(2)). We constructed chimeric proteins and mutants to address the protein region that specifies which reactive oxygen species is produced. Reactive oxygen species were measured with luminol/horseradish peroxidase and Amplex Red for H(2)O(2) versus L-012 and cytochrome c for O(2)(·-).

Hepatocyte growth factor induces a proangiogenic phenotype and mobilizes endothelial progenitor cells by activating Nox2.

Hepatocyte growth factor (HGF) by stimulating the receptor tyrosine kinase c-Met induces angiogenesis and tissue regeneration. HGF has been shown to antagonize the angiotensin II-induced senescence of endothelial progenitor cells (EPCs), which is mediated by NADPH oxidase-dependent reactive oxygen species (ROS) formation. As growth factors, however, usually require ROS for their signaling, we hypothesized that the proangiogenic effects of HGF require NADPH oxidases and focused on the homolog Nox2, which is most abundantly expressed in EPCs and endothelial cells.