Sex-specific cardiovascular adaptations to simulated microgravity in Sprague-Dawley rats.

Men and women have different cardiovascular responses to spaceflight; however, few studies have focused on direct comparisons between sexes. We investigated the mechanisms of aortic stiffening in socially and sexually mature 20-week-old male and female Sprague Dawley (SD) rats exposed to hindlimb unloading (HLU) for 14 days. Pulse wave velocity (PWV) was greater in the aortic arch of females after HLU versus control females (n = 6-8).

Discrete Correlate Summation Clustering of a Dopamine-Angiotensin Network.

We present a model of directed investigation of KEGG pathway analysis, beginning with discrete correlate summation (DCS) clustering of Swiss-Prot sets. Dopamine and angiotensin related proteins define the boundary for pathway analyses upon a network of proteins also associated with a compositely defined matrix of Swiss-Prot keywords to provide a framework for their biological indices (Figure 1).

Photoacoustic imaging for non-invasive assessment of biomarkers of intestinal injury in experimental necrotizing enterocolitis.

Background: Necrotizing enterocolitis (NEC) is an often-lethal disease of the premature infant intestinal tract, exacerbated by significant diagnostic difficulties. In NEC, the intestine exhibits hypoperfusion and dysmotility, contributing to disease pathogenesis. However, these features cannot be accurately and quantitively assessed with current imaging modalities.

Photoacoustic Imaging for Non-Invasive Assessment of Physiological Biomarkers of Intestinal Injury in Experimental Necrotizing Enterocolitis.

Background: Necrotizing enterocolitis (NEC) is an often-lethal disease of the premature infants' intestinal tract that is exacerbated by significant difficulties in early and accurate diagnosis. In NEC disease, the intestine often exhibits hypoperfusion and dysmotility, which contributes to advanced disease pathogenesis. However, these physiological features cannot be accurately and quantitively assessed within the current constraints of imaging modalities frequently used in the clinic (plain film X-ray and ultrasound).

Photoacoustic Imaging as a Novel Non-invasive Biomarker to Assess Intestinal Tissue Oxygenation and Motility in Neonatal Rats.

Background: Within the premature infant intestine, oxygenation and motility play key physiological roles in healthy development and disease such as necrotizing enterocolitis. To date, there are limited techniques to reliably assess these physiological functions that are also clinically feasible for critically ill infants. To address this clinical need, we hypothesized that photoacoustic imaging (PAI) can provide non-invasive assessment of intestinal tissue oxygenation and motility to characterize intestinal physiology and health.

Photoacoustic Imaging as a Novel Non-Invasive Biomarker to Assess Intestinal Tissue Oxygenation and Motility in Neonatal Rats.

Background: Within the premature infant intestine, oxygenation and motility play key physiological roles in healthy development and disease such as necrotizing enterocolitis. To date, there are limited techniques to reliably assess these physiological functions that are also clinically feasible for critically ill infants. To address this clinical need, we hypothesized that photoacoustic imaging (PAI) can provide non-invasive assessment of intestinal tissue oxygenation and motility to characterize intestinal physiology and health.

Targeting the CD47/thrombospondin-1 signaling axis regulates immune cell bioenergetics in the tumor microenvironment to potentiate antitumor immune response.

Background: CD47 is an integral membrane protein that alters adaptive immunosurveillance when bound to the matricellular glycoprotein thrombospondin-1 (TSP1). We examined the impact of the CD47/TSP1 signaling axis on melanoma patient response to anti-PD-1 therapy due to alterations in T cell activation, proliferation, effector function, and bioenergetics.

Methods: A syngeneic B16 mouse melanoma model was performed to determine if targeting CD47 as monotherapy or in combination with anti-PD-1 impacted tumor burden.

Differential Expression of CB Cannabinoid Receptor and Cannabinoid Receptor Interacting Protein 1a in Labor.

The endocannabinoid system is present in multiple organ systems and is involved in smooth muscle regulation, immune function, neuroendocrine modulation, and metabolism of tissues. Limited data are available regarding the presence and role of this system in reproductive tissues. Components of the endocannabinoid system have been identified in myometrial and placental tissues.

Longitudinal study of angiotensin peptides in normal and pre-eclamptic pregnancy.

Purpose: To address whether differential regulation of the renin-angiotensin-aldosterone system occurs in pre-eclampsia, we performed an analysis of the time course of circulating and urinary profiles of the vasoconstrictor (Ang II) and the vasodilator [Ang-(1-7)] peptides in normal pregnant (NP) and pre-eclamptic (PE) women.

Methods: Urine and plasma samples from 86 nulliparous women were collected prospectively; 67 subjects continued as NP and 19 developed PE. Subjects were enrolled prior to 12 weeks of gestation and plasma and spot urine samples were obtained throughout gestation.

Systemic Outcomes of (Pyr)-Apelin-13 Infusion at Mid-Late Pregnancy in a Rat Model with Preeclamptic Features.

Preeclampsia is a syndrome with diverse clinical presentation that currently has no cure. The apelin receptor system is a pleiotropic pathway with a potential for therapeutic targeting in preeclampsia. We established the systemic outcomes of (Pyr)-apelin-13 administration in rats with preeclamptic features (TGA-PE, female transgenic for human angiotensinogen mated to male transgenic for human renin).

Preclinical Ultrasound-Guided Photoacoustic Imaging of the Placenta in Normal and Pathologic Pregnancy.

Placental oxygenation varies throughout pregnancy. The detection of early changes in placental oxygenation as pregnancy progresses is important for early identification of preeclampsia or other complications. This invited commentary discusses a recent preclinical study on the application of 3-dimensional photoacoustic imaging (PAI) for assessment of regional variations in placental oxygenation and longitudinal analysis of differences in placental oxygenation throughout normal pregnancy and pregnancy associated with hypertension or placental insufficiency in mice.

Photoacoustic imaging for quantification of placental oxygenation in mice.

Accurate analysis of placental and fetal oxygenation is critical during pregnancy. Photoacoustic imaging (PAI) combines laser technology with ultrasound in real time. We tested the sensitivity and accuracy of PAI for analysis of placental and fetal oxygen saturation (sO) in mice.

Local intra-uterine Ang-(1-7) infusion attenuates PGE and 6-keto PGF in decidualized uterus of pseudopregnant rats.

Background: Cyclooxygenase (COX)-derived prostanoids (PGE PGI) are important contributors to the process of decidualization. Previous studies showed the presence of Ang-(1-7) in the primary and secondary decidualized zones of the implantation site at early pregnancy. Decreased concentrations of Ang-(1-7) were found in the decidualized uterus compared to the non-decidualized uterus of pseudopregnant rats, suggesting that low levels of Ang-(1-7) are required for successful decidualization at early pregnancy.

Photoacoustic Imaging for the Detection of Hypoxia in the Rat Femoral Artery and Skeletal Muscle Microcirculation.

Photoacoustic (PA) imaging is an emerging technology that combines structural and functional imaging of tissues using laser and ultrasound energy. We evaluated the ability of PA imaging system to measure real-time systemic and microvascular mean oxygen saturation (mSAO2) in a rat model of hypoxic shock. Male Sprague Dawley rats (n = 6) underwent femoral artery catherization and were subjected to acute hypoxia by lowering the fraction of inspired oxygen (FiO2) from 1.

Apelin-13 in blood pressure regulation and cardiovascular disease.

Purpose Of Review: Despite extensive pharmacological treatment, hypertension and heart failure still pose as high health and economic burden. Thus, novel therapeutic approaches are needed to promote more effective treatment of hypertension and cardiovascular disease. In this review we summarized recent evidence supporting the therapeutic potential of apelin-13, a recently discovered endogenous ligand for the G-protein coupled receptor APJ.

Functional changes in the uterine artery precede the hypertensive phenotype in a transgenic model of hypertensive pregnancy.

The pregnant female human angiotensinogen (hAGN) transgenic rat mated with the male human renin (hREN) transgenic rat is a model of preeclampsia (TgA) with increased blood pressure, proteinuria, and placenta alterations of edema and necrosis at late gestation. We studied vascular responses and the role of COX-derived prostanoids in the uterine artery (UA) at early gestation in this model. TgA UA showed lower stretch response, similar smooth muscle α-actin content, and lower collagen content compared with Sprague-Dawley (SD) UA.

Downregulation of apelin in the human placental chorionic villi from preeclamptic pregnancies.

The role of the endogenous apelin system in pregnancy is not well understood. Apelin's actions in pregnancy are further complicated by the expression of multiple forms of the peptide. Using radioimmunoassay (RIA) alone, we established the expression of apelin content in the chorionic villi of preeclamptic (PRE) and normal pregnant women (NORM) at 36-38 wk of gestation.

Superoxide overproduction and kidney fibrosis: a new animal model.

Objective: To establish whether the mutation in the Immp2L gene induces renal fibrosis and whether aging exacerbates renal morphology in mice.

Methods: Female mutant mice with mutation in the inner mitochondrial membrane peptidase 2-like protein at 3 and 18 months of age were used. Renal fibrosis was analyzed using classic fibrosis score, Masson's trichrome staining, and analysis of profibrotic markers using real time polymerase chain reaction (superoxide dismutase 1, metalloproteinase-9, erythropoietin, transforming growth factor beta), and immunostaining (fibroblasts and Type IV collagen).

Uterine artery dysfunction in pregnant ACE2 knockout mice is associated with placental hypoxia and reduced umbilical blood flow velocity.

Angiotensin-converting enzyme 2 (ACE2) knockout is associated with reduced fetal weight at late gestation; however, whether uteroplacental vascular and/or hemodynamic disturbances underlie this growth-restricted phenotype is unknown. Uterine artery reactivity and flow velocities, umbilical flow velocities, trophoblast invasion, and placental hypoxia were determined in ACE2 knockout (KO) and C57Bl/6 wild-type (WT) mice at day 14 of gestation. Although systolic blood pressure was higher in pregnant ACE2 KO vs.

Local uterine Ang-(1-7) infusion augments the expression of cannabinoid receptors and differentially alters endocannabinoid metabolizing enzymes in the decidualized uterus of pseudopregnant rats.

Background: Endocannabinoids (ECs) are important contributors to implantation and decidualization and are suppressed in early pregnancy. Elevated levels of anandamide (AEA), the endogenous ligand for the CB1 and CB2 receptors (R), interfere with receptivity of the blastocyst. Ang-(1-7) is down-regulated in the implantation site (IS) in normal pregnancy at day 7 of gestation.

Increased angiotensin II contraction of the uterine artery at early gestation in a transgenic model of hypertensive pregnancy is reduced by inhibition of endocannabinoid hydrolysis.

Increased vascular sensitivity to angiotensin II (Ang II) is a marker of a hypertensive human pregnancy. Recent evidence of interactions between the renin-angiotensin system and the endocannabinoid system suggests that anandamide and 2-arachidonoylglycerol may modulate Ang II contraction. We hypothesized that these interactions may contribute to the enhanced vascular responses in hypertensive pregnancy.

Hemodynamic responses to angiotensin-(1-7) in women in their third trimester of pregnancy.

Background: To understand the role of Angiotensin-(1-7) (Ang-(1-7)) in vasculature of pregnant women, we compared cardiac output (CO), total peripheral resistance (TPR) and forearm blood flow (FBF) responses to Ang-(1-7) infusion between normotensive pregnant women in their third trimester and healthy age matched non-pregnant women. The responses of skin microcirculation to Ang-(1-7) were tested in preeclamptic, normotensive pregnant and non-pregnant women. Responses to Angiotensin II (Ang II) were also determined.

Cell therapy with human renal cell cultures containing erythropoietin-positive cells improves chronic kidney injury.

New therapeutic strategies for chronic kidney disease (CKD) are necessary to offset the rising incidence of CKD and donor shortage. Erythropoietin (EPO), a cytokine produced by fibroblast-like cells in the kidney, has recently emerged as a renoprotective factor with anti-inflammatory, antioxidant properties. This study (a) determined whether human renal cultures (human primary kidney cells [hPKC]) can be enriched in EPO-positive cells (hPKC(F+)) by using magnetic-bead sorting; (b) characterized hPKC(F+) following cell separation; and (c) established that intrarenal delivery of enriched hPKC(F+) cells would be more beneficial in treatment of renal injury, inflammation, and oxidative stress than unsorted hPKC cultures in a chronic kidney injury model.