Sterile inflammation induces vasculopathy and chronic lung injury in murine sickle cell disease.

Murine sickle cell disease (SCD) results in damage to multiple organs, likely mediated first by vasculopathy. While the mechanisms inducing vascular damage remain to be determined, nitric oxide bioavailability and sterile inflammation are both considered to play major roles in vasculopathy. Here, we investigate the effects of high mobility group box-1 (HMGB1), a pro-inflammatory damage-associated molecular pattern (DAMP) molecule on endothelial-dependent vasodilation and lung morphometrics, a structural index of damage in sickle (SS) mice.

Ciliogenesis mechanisms mediated by PAK2-ARL13B signaling in brain endothelial cells is responsible for vascular stability.

In the developing vasculature, cilia, microtubule-based organelles that project from the apical surface of endothelial cells (ECs), have been identified to function cell autonomously to promote vascular integrity and prevent hemorrhage. To date, the underlying mechanisms of endothelial cilia formation (ciliogenesis) are not fully understood. Understanding these mechanisms is likely to open new avenues for targeting EC-cilia to promote vascular stability.

Cilia proteins are biomarkers of altered flow in the vasculature.

Cilia, microtubule-based organelles that project from the apical luminal surface of endothelial cells (ECs), are widely regarded as low-flow sensors. Previous reports suggest that upon high shear stress, cilia on the EC surface are lost, and more recent evidence suggests that deciliation-the physical removal of cilia from the cell surface-is a predominant mechanism for cilia loss in mammalian cells. Thus, we hypothesized that EC deciliation facilitated by changes in shear stress would manifest in increased abundance of cilia-related proteins in circulation.

Established, New and Emerging Concepts in Brain Vascular Development.

In this review, we discuss the state of our knowledge as it relates to embryonic brain vascular patterning in model systems zebrafish and mouse. We focus on the origins of endothelial cell and the distinguishing features of brain endothelial cells compared to non-brain endothelial cells, which is revealed by single cell RNA-sequencing methodologies. We also discuss the cross talk between brain endothelial cells and neural stem cells, and their effect on each other.

Growth Hormone and Insulin-like Growth Factor-I Molecular Weight Isoform Responses to Resistance Exercise Are Sex-Dependent.

To determine if acute resistance exercise-induced increases in growth hormone (GH) and insulin-like growth factor-I (IGF-I) were differentially responsive for one or more molecular weight (MW) isoforms and if these responses were sex-dependent. College-aged men ( = 10) and women ( = 10) performed an acute resistance exercise test (ARET; 6 sets, 10 repetition maximum (10-RM) squat, 2-min inter-set rest). Serum aliquots from blood drawn Pre-, Mid-, and Post-ARET (0, +15, and +30-min post) were processed using High Performance Liquid Chromatography (HPLC) fractionation and pooled into 3 MW fractions (Fr.

Interaction of tumor cells and astrocytes promotes breast cancer brain metastases through TGF-β2/ANGPTL4 axes.

Metastatic outcomes depend on the interactions of metastatic cells with a specific organ microenvironment. Our previous studies have shown that triple-negative breast cancer (TNBC) MDA-MB-231 cells passaged in astrocyte-conditioned medium (ACM) show proclivity to form brain metastases, but the underlying mechanism is unknown. The combination of microarray analysis, qPCR, and ELISA assay were carried out to demonstrate the ACM-induced expression of angiopoietin-like 4 (ANGPTL4) in TNBC cells.

Characterization of growth hormone disulfide-linked molecular isoforms during post-exercise release vs nocturnal pulsatile release reveals similar milieu composition.

Objective: To characterize the influence of mode (aerobic/resistance) and volume of exercise (moderate/high) on circulating GH immediately post-exercise as well as following the onset of sleep.

Design: This study used repeated measures in which subjects randomly completed 5 separate conditions: control (no exercise), moderate volume resistance exercise (MR), high-volume resistance exercise (HR), moderate volume aerobic exercise (MA), and high volume aerobic exercise (HA).

Methods: Subjects had two overnight stays on each of the 5 iterations.

Regulation of Cerebral Blood Flow: Response to Cytochrome P450 Lipid Metabolites.

There have been numerous reviews related to the cerebral circulation. Most of these reviews are similar in many ways. In the present review, we thought it important to provide an overview of function with specific attention to details of cerebral arterial control related to brain homeostasis, maintenance of neuronal energy demands, and a unique perspective related to the role of astrocytes.

Differential basal and exercise-induced IGF-I system responses to resistance vs. calisthenic-based military readiness training programs.

Objective: The purpose of this study was to: 1) evaluate differential responses of the IGF-I system to either a calisthenic- or resistance exercise-based program and 2) determine if this chronic training altered the IGF-I system during an acute resistance exercise protocol.

Design: Thirty-two volunteers were randomly assigned into a resistance exercise-based training (RT) group (n=15, 27±5y, 174±6cm, 81±12kg) or a calisthenic-based training group (CT) (n=17, 29±5y, 179±8cm, 85±10kg) and all underwent 8weeks of exercise training (1.5h/d, 5d/wk).

Expression of CYP 4A ω-hydroxylase and formation of 20-hydroxyeicosatetreanoic acid (20-HETE) in cultured rat brain astrocytes.

Astrocytes secrete vasodilator and vasoconstrictor factors via end feet processes, altering blood flow to meet neuronal metabolic demand. Compared to what is known about the ability of astrocytes to release factors that dilate local cerebral vasculature, very little is known regarding the source and identity of astrocyte derived constricting factors. The present study investigated if astrocytes express CYP 4A ω-hydroxylase and metabolize arachidonic acid (AA) to 20-hydroxyeicotetraenoic acid (20-HETE) that regulates KCa channel activity in astrocytes and cerebral arterial myocyte contractility.

Elevated Aminopeptidase P Attenuates Cerebral Arterial Responses to Bradykinin in Fawn-Hooded Hypertensive Rats.

Cerebral arterial myogenic and autoregulatory responses are impaired in Fawn Hooded hypertensive (FHH) rats. Cerebral autoregulatory responses are restored in the congenic rat strain in which a segment of chromosome 1 from the Brown Norway (BN) rat was transferred into the FHH genetic background (FHH.1BN).

Twenty-hour growth hormone secretory profiles after aerobic and resistance exercise.

Introduction: The pulsatile secretion pattern of growth hormone (GH) is an important parameter of GH action at peripheral tissues, and more information is needed on how exercise impacts GH secretion. This study hypothesized that both aerobic and resistance exercise would exhibit dose-response relationships with respect to exercise duration and 20-h postexercise GH secretion.

Methods: Eight healthy men randomly completed five separate conditions: 1) control (no exercise; CON), 2) a moderate-duration (1-h) aerobic exercise session (MA), 3) a long-duration (2-h) aerobic exercise session (LA), 4) a moderate-duration (1-h) resistance exercise session (MR), and 5) a long-duration (2-h) resistance exercise session (LR).

Astrocytes directly influence tumor cell invasion and metastasis in vivo.

Brain metastasis is a defining component of tumor pathophysiology, and the underlying mechanisms responsible for this phenomenon are not well understood. Current dogma is that tumor cells stimulate and activate astrocytes, and this mutual relationship is critical for tumor cell sustenance in the brain. Here, we provide evidence that primary rat neonatal and adult astrocytes secrete factors that proactively induced human lung and breast tumor cell invasion and metastasis capabilities.

Epoxyeicosatrienoic acids pretreatment improves amyloid β-induced mitochondrial dysfunction in cultured rat hippocampal astrocytes.

Amyloid-β (Aβ) has long been implicated as a causative protein in Alzheimer's disease. Cellular Aβ accumulation is toxic and causes mitochondrial dysfunction, which precedes clinical symptoms of Alzheimer's disease pathology. In the present study, we explored the possible use of epoxyeicosatrienoic acids (EETs), epoxide metabolites of arachidonic acid, as therapeutic target against Aβ-induced mitochondrial impairment using cultured neonatal hippocampal astrocytes.

Exercise-induced insulin-like growth factor I system concentrations after training in women.

Introduction: This study examined the effects of short-term physical training on the acute hormonal response (i.e., growth hormone, total and free insulin-like growth factor I [IGF-I], and IGF binding proteins [IGFBP]-1, IGFBP-2, and IGFBP-3) to resistance exercise (RE) in women.

Effects of acute caloric restriction compared to caloric balance on the temporal response of the IGF-I system.

Objective: Insulin-like growth factor-I (IGF-I) is a key regulator of metabolism during altered energy states. The IGF-I system components respond to prolonged caloric restriction but it is not clear if this system responds similarly to acute caloric restriction. The purpose of this study was to characterize the IGF-I system response to acute caloric restriction with a secondary purpose of determining if two isocaloric diets with different ratios of carbohydrate to fat alter the IGF-I system under conditions of caloric balance.

Noninvasive assessment of vascular structure and function in conscious rats based on in vivo imaging of the albino iris.

Experimental techniques allowing longitudinal studies of vascular disease progression or treatment effects are not readily available for most animal models. Thus, most existing studies are destined to either study individual time points or use large cohorts of animals. Here we describe a noninvasive technique for studying vascular disease that is based on in vivo imaging of the long posterior ciliary artery (LPCA) in the iris of albino rats.

Effect of the data sampling rate on accuracy of indices for heart rate and blood pressure variability and baroreflex function in resting rats and mice.

The aim of this study was to determine the minimal sampling rate (SR) required for blood pressure (BP) waveform recordings to accurately determine BP and heart rate (HR) variability indices and baroreceptor reflex sensitivity in rats and mice. We also determined if an 8-bit (versus 12-bit) analog-to-digital converter (ADC) resolution is sufficient to accurately determine these hemodynamic parameters and if spline interpolation to 1000 Hz of BP waveforms sampled at lower SRs can improve accuracy. BP and ECG recordings (1000 Hz SR, 12-bit ADC resolution) from two strains of rats and BP recordings (1000 Hz SR, 12-bit ADC resolution) from two strains of mice were mathematically converted to lower SRs and/or 8-bit ADC resolution.

Circulating bioactive and immunoreactive IGF-I remain stable in women, despite physical fitness improvements after 8 weeks of resistance, aerobic, and combined exercise training.

Insulin-like growth factor-I (IGF-I) is regulated by a number of IGF-binding proteins (IGFBPs) and proteases that influence IGF-I bioactivity. A specific IGF-I kinase receptor activation assay (KIRA) has been developed that determines the ability of IGF-I to activate the IGF-I receptor by quantification of intracellular receptor autophosphorylation on IGF-I binding. KIRA-assessed IGF-I bioactivity has not been utilized within the context of chronic exercise training paradigms.

Frequency response characteristics of whole body autoregulation of blood flow in rats.

Previously, we demonstrated that very low-frequency (VLF) blood pressure variability (BPV) depends on voltage-gated L-type Ca(2+)-channels, suggesting that autoregulation of blood flow and/or myogenic vascular function significantly contributes to VLF BPV. To further substantiate this possibility, we tested the hypothesis that the frequency response characteristic of whole body autoregulation of blood flow is consistent with the frequency range of VLF BPV (0.02-0.

Effects of acute and chronic exercise on disulfide-linked growth hormone variants.

Purpose: To test the hypothesis that the appearance of disulfide-linked growth hormone (GH) aggregates during and after an acute resistance exercise test (ARET) in men could be influenced by chronic physical training.

Methods: Fourteen men (28 +/- 1 yr) underwent two different 8-wk physical training programs designed to improve military performance. Before and after chronic training, subjects performed an ARET (six sets of 10 repetition-maximum squat) and had venous blood drawn pre-, mid-, and post-ARET (0, 15, and 30 min postexercise).

Energy flux, more so than energy balance, protein intake, or fitness level, influences insulin-like growth factor-I system responses during 7 days of increased physical activity.

The purpose of this study was to determine the impact of dietary factors and exercise-associated factors on the response of IGF-I and its binding proteins (IGFBPs) during a period of increased physical activity. Twenty-nine men completed a 4-day (days 1-4) baseline period of a controlled energy balanced diet while maintaining their normal physical activity level followed by 7 days (days 5-11) of a 1,000 kcal/day increase in physical activity above their normal activity levels. Two subject groups, one sedentary (Sed, mean Vo(2peak): 39 mlxkg(-1)xmin(-1), n = 7) and one fit (FIT1, mean Vo(2peak): 56 ml.