Inhibition of BDNF signaling in the paraventricular nucleus of the hypothalamus lowers acute stress-induced pressor responses.

Brain-derived neurotrophic factor (BDNF) expression increases in the paraventricular nucleus of the hypothalamus (PVN) during stress, and our recent studies indicate that BDNF induces sympathoexcitatory and hypertensive responses when injected acutely or overexpressed chronically in the PVN. However, it remained to be investigated whether BDNF is involved in the mediation of stress-induced cardiovascular responses. Here we tested the hypothesis that inhibition of the high-affinity BDNF receptor TrkB in the PVN diminishes acute stress-induced cardiovascular responses.

BDNF acting in the hypothalamus induces acute pressor responses under permissive control of angiotensin II.

Brain-derived neurotrophic factor (BDNF) expression increases in the paraventricular nucleus of the hypothalamus (PVN) during hypertensive stimuli including stress and hyperosmolarity, but its role in PVN cardiovascular regulatory mechanisms is unclear. Chronic BDNF overexpression in the PVN has been shown to elevate sympathetic tone and blood pressure in part by modulating central angiotensin (Ang) II mechanisms. However, the cardiovascular effects of short-term increases in PVN levels of BDNF and the mechanisms governing them are unknown.

Threonyl-tRNA synthetase overexpression correlates with angiogenic markers and progression of human ovarian cancer.

Background: Ovarian tumors create a dynamic microenvironment that promotes angiogenesis and reduces immune responses. Our research has revealed that threonyl-tRNA synthetase (TARS) has an extracellular angiogenic activity separate from its function in protein synthesis. The objective of this study was to test the hypothesis that TARS expression in clinical samples correlates with angiogenic markers and ovarian cancer progression.

Differential regulation of GLUT1 and GLUT8 expression by hypoxia in mammary epithelial cells.

Glucose is a major substrate for milk synthesis and is taken up from the blood by mammary epithelial cells (MECs) through facilitative glucose transporters (GLUTs). The expression levels of GLUT1 and GLUT8 are upregulated dramatically in the mammary gland from late pregnancy through early lactation stages. This study aimed to test the hypothesis that this increase in GLUT1 and GLUT8 expression involves hypoxia signaling through hypoxia inducible factor-1α (HIF-1α) in MECs.

Negative regulation of HIF-1α by an FBW7-mediated degradation pathway during hypoxia.

Hypoxia inducible factor-1α (HIF-1α) stimulates expression of genes associated with angiogenesis and is associated with poor outcomes in ovarian and other cancers. In normoxia, HIF-1α is ubiquitinated and degraded through the E3 ubiquitin ligase, von Hippel-Lindau; however, little is known about the regulation of HIF-1α in hypoxic conditions. FBW7 is an E3 ubiquitin ligase that recognizes proteins phosphorylated by glycogen synthase kinase 3β (GSK3β) and targets them for destruction.

Genes overexpressed in cerebral arteries following salt-induced hypertensive disease are regulated by angiotensin II, JunB, and CREB.

Although changes in gene expression are necessary for arterial remodeling during hypertension, the genes altered and their mechanisms of regulation remain uncertain. The goal of this study was to identify cerebral artery genes altered by hypertension and define signaling pathways important in their regulation. Intact cerebral arteries from Dahl salt-sensitive normotensive and hypertensive high-salt (HS) rats were examined by immunostaining, revealing an increased phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and expression of the proliferative marker Ki-67 in arteries from hypertensive animals.

Emergence of a R-type Ca2+ channel (CaV 2.3) contributes to cerebral artery constriction after subarachnoid hemorrhage.

Cerebral aneurysm rupture and subarachnoid hemorrhage (SAH) inflict disability and death on thousands of individuals each year. In addition to vasospasm in large diameter arteries, enhanced constriction of resistance arteries within the cerebral vasculature may contribute to decreased cerebral blood flow and the development of delayed neurological deficits after SAH. In this study, we provide novel evidence that SAH leads to enhanced Ca2+ entry in myocytes of small diameter cerebral arteries through the emergence of R-type voltage-dependent Ca2+ channels (VDCCs) encoded by the gene CaV 2.

VEGF and HIF-1alpha expression are increased in advanced stages of epithelial ovarian cancer.

Objective: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that is elevated in epithelial ovarian cancer. Hypoxia inducible factor-1alpha (HIF-1alpha) is a transcription factor that plays a regulatory role in the expression of VEGF. Currently, there is limited information regarding VEGF and HIF-1alpha expression in epithelial ovarian cancer specimens.

Nitric oxide and reactive oxygen species exert opposing effects on the stability of hypoxia-inducible factor-1alpha (HIF-1alpha) in explants of human pial arteries.

Hypoxia induces angiogenesis, partly through stabilization of hypoxia-inducible factor-1alpha (HIF-1alpha), leading to transcription of pro-angiogenic factors. Here we examined the regulation of HIF-1alpha by hypoxia and nitric oxide (NO) in explants of human cerebrovascular smooth muscle cells. Cells were treated with NO donors under normoxic or hypoxic (2% O2) conditions, followed by analysis of HIF-1alpha protein levels.