Perivascular neurons instruct 3D vascular lattice formation via neurovascular contact.

The vasculature of the central nervous system is a 3D lattice composed of laminar vascular beds interconnected by penetrating vessels. The mechanisms controlling 3D lattice network formation remain largely unknown. Combining viral labeling, genetic marking, and single-cell profiling in the mouse retina, we discovered a perivascular neuronal subset, annotated as Fam19a4/Nts-positive retinal ganglion cells (Fam19a4/Nts-RGCs), directly contacting the vasculature with perisomatic endfeet.

Systemic vasoprotection by inhaled carbon monoxide is mediated through prolonged alterations in monocyte/macrophage function.

Carbon monoxide (CO) is anti-inflammatory and protective in models of disease. Its actions in vitro are short-lived but are sustained in vivo. We hypothesize that systemic CO can mediate prolonged phenotype changes in vivo, with a focus on macrophages (Mφs).

Xanthine Oxidoreductase Function Contributes to Normal Wound Healing.

Chronic, nonhealing wounds result in patient morbidity and disability. Reactive oxygen species (ROS) and nitric oxide (NO) are both required for normal wound repair, and derangements of these result in impaired healing. Xanthine oxidoreductase (XOR) has the unique capacity to produce both ROS and NO.

High mobility group box 1 promotes endothelial cell angiogenic behavior in vitro and improves muscle perfusion in vivo in response to ischemic injury.

Objectives: The angiogenic drive in skeletal muscle ischemia remains poorly understood. Innate inflammatory pathways are activated during tissue injury and repair, suggesting that this highly conserved pathway may be involved in ischemia-induced angiogenesis. We hypothesize that one of the endogenous ligands for innate immune signaling, high mobility group box 1 (HMGB1), in combination with autophagic responses to hypoxia or nutrient deprivation, plays an important role in angiogenesis.

Cyclic AMP inhibits IL-1beta plus IFNgamma-induced NF-kappaB translocation in hepatocytes by a PKA independent mechanism.

We previously showed that cAMP inhibits IL-1beta plus IFNgamma-induced NF-kappaB binding in primary hepatocytes but the signaling mechanisms responsible for this effect are not understood. In this study, the role of PKA in mediating the effect of cAMP on NF-kappaB was investigated. Immunofluorescent staining showed that cAMP inhibited IL-1beta plus IFNgamma-induced translocation of NF-kappaB into the nucleus.

Unfolding the pathophysiological role of bioactive lysophospholipids.

Lysophospholipids (LPLs), including glycerol- and sphingoid-based lipids, stimulate cell signaling and play important pathophysiological roles in humans and other animals. These LPLs include lysophosphatidic acid (LPA), lysophosphatidylinositol (LPI), lysophosphatidylcholine (LPC), lysophosphatidylserine (LPS), sphingosine-1-phosphate (S1P), and sphingosylphosphorylcholine (SPC). Analyses of LPLs in human body fluids from subjects with different pathophysiological conditions reveal not only the relevance of LPLs in human diseases, but also their potential application as biomarkers and/or therapeutic targets.

Role of ether-linked lysophosphatidic acids in ovarian cancer cells.

Naturally occurring alkyl- and alkenyl-lysophosphatidic acids (al-LPAs) are detected and elevated in ovarian cancer ascites compared with ascites from non-malignant diseases. Here we describe the biological functions and signaling properties of these ether-linked LPAs in ovarian cancer cells. They are elevated and stable in ovarian cancer ascites, which represents an in vivo environment for ovarian cancer cells.