scholarly journals Endothelial phenotype differs by both sex and vessel function

2017 ◽  
Author(s):  
◽  
Scott S. Kemp
Keyword(s):  
Endothelial Cells ◽  
Primary Cultures ◽  
Female Rats ◽  
Pharmacological Agents ◽  
Disease States ◽  
Male And Female Rats ◽  
Size Growth ◽  
Flowing Blood ◽  
Cell Phenotypes ◽  
Conduit Vessel

Endothelial cells (the cells that line our blood vessels) were once thought to be an inert cellophane-like wrapper separating flowing blood from tissue. However, as our understanding of the human body has progressed, we have come to know that the endothelium is actually an incredibly important, metabolic ally active organ. Endothelial dysfunction appears to be an early hallmark of multiple disease states, including, but not limited to, cardiovascular disease, type II diabetes, and atherosclerosis. While it is often presumed that all non-specialized endothelial cells are the same, and thus will have the same response to various pharmacological agents, disease states, and stimuli, this may not be true. Our goal is to understand if endothelial cell phenotypes (characteristics expressed by the cell) vary based on their origin (the blood vessel they come from), or by sex, and if so, to what degree. Specifically, our research focused on primary cultures of aortic (a conduit vessel) endothelial cells and of skeletal muscle microvasculature (exchange vessels) endothelial cells from both male and female rats, then compared them to one another, after being grown under identical conditions. Our results strongly suggest that endothelial cells vary in size, growth rates, and protein expression, based on their origin and their sex. The implication is that medicines could affect different parts of our bodies indifferent ways, as well as affecting males and females differently. When studying functions mediated by vascular endothelium, it is important to use cells from an anatomical/functional location that best describes the question under investigation (or multiple locations if looking systemically), AND both sexes, as both characteristics determine the phenotype.

Plasticity of endothelial cells: rapid dedifferentiation of freshly isolated high endothelial venule endothelial cells outside the lymphoid tissue microenvironment

Blood ◽  
2004 ◽  
Vol 103 (11) ◽  
pp. 4164-4172 ◽  
Author(s):  
Delphine-Armelle Lacorre ◽  
Espen S. Baekkevold ◽  
Ignacio Garrido ◽  
Per Brandtzaeg ◽  
Guttorm Haraldsen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Lymphoid Tissue ◽  
Ex Vivo ◽  
Primary Cultures ◽  
High Endothelial Venule ◽  
Tissue Specific ◽  
Tissue Microenvironment ◽  
Cell Phenotypes

Abstract Endothelial cells display remarkable heterogeneity in different organs and vascular beds. Although many studies suggest that tissues “speak” to endothelial cells, endothelial cell diversity remains poorly characterized at the molecular level. Here, we describe a novel strategy to characterize tissue-specific endothelial cell phenotypes and to identify endothelial cell genes that are under the control of the local microenvironment. By comparing post-capillary high endothelial venule endothelial cells (HEVECs), freshly isolated from human tonsils without any cell culture step, with HEVECs cultured for 2 days, we found that HEVECs rapidly lost their specialized characteristics when isolated from the lymphoid tissue microenvironment. Striking changes occurred as early as after 48 hours, with complete loss of the postcapillary venule–specific Duffy antigen receptor for chemokines (DARCs) and the HEV-specific fucosyltransferase Fuc-TVII. DNA microarray analysis identified several other candidate HEV genes that were rapidly down-regulated ex vivo, including type XV collagen, which we characterized as a novel, abundant HEV transcript in situ. Together, our results demonstrate that blood vessel type–specific and tissue-specific characteristics of endothelial cells are under the control of their microenvironment. Therefore, even short-term primary cultures of human endothelial cells may not adequately mimic the differentiated endothelial cell phenotypes existing in vivo.

scholarly journals Increasing Endocannabinoid Tone Alters Anxiety-Like and Stress Coping Behaviour in Female Rats Prenatally Exposed to Valproic Acid

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3720
Author(s):  
Aoife M. Thornton ◽  
Rachel M. Humphrey ◽  
Daniel M. Kerr ◽  
David P. Finn ◽  
Michelle Roche
Keyword(s):  
Valproic Acid ◽  
Stress Test ◽  
Female Rats ◽  
Stress Coping ◽  
Pharmacological Agents ◽  
Coping Behaviour ◽  
Behavioural Responses ◽  
Novel Treatments ◽  
Specific Effects ◽  
Male And Female Rats

Given the sex differences evident in the prevalence of autism, there is an increased awareness of the importance of including females in autism research to determine sexual dimorphism and sex-specific treatments. Cannabinoids and endocannabinoid modulators have been proposed as potential novel treatments for autism-related symptoms; however, few studies to date have examined if these pharmacological agents elicit sex-specific effects. The aim of the present study was to use the valproic acid (VPA) model of autism to compare the behavioural responses of male and female rats and examine the effects of increasing endocannabinoid tone on the behavioural responses of VPA-exposed female rats. These data revealed that VPA-exposed male, but not female, rats exhibit reduced social responding in the three-chamber and olfactory habituation/dishabituation (OHD) test during adolescence. In comparison, VPA-exposed female, but not male, adolescent rats exhibited anxiety-like behaviour in the elevated plus maze (EPM) and open field test (OFT). In VPA-exposed female rats, increasing 2-AG levels augmented anxiety-like behaviour in the EPM and OFT, while increasing AEA levels reduced stress coping behaviour in the swim stress test. These data highlight sexual dimorphic behaviours in the VPA model and indicate that enhancing endocannabinoid levels may exacerbate negative affective behaviour in VPA-exposed females. Thus, considerations should be paid to the possible sex-specific effects of cannabinoids for the treatment of symptoms associated with autism.

Acute effects of testosterone on intracellular Ca2+ kinetics in rat coronary endothelial cells are exerted via aromatization to estrogens

2004 ◽  
Vol 287 (1) ◽  
pp. H63-H71 ◽  
Author(s):  
Alfredo Sierra-Ramírez ◽  
Tomás Morato ◽  
Rafael Campos ◽  
Iván Rubio ◽  
Claudia Calzada ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
In Situ Hybridization ◽  
Polyclonal Antibodies ◽  
Chelating Agent ◽  
Female Rats ◽  
Significant Activity ◽  
Acetoxymethyl Ester ◽  
Male And Female Rats ◽  
Gender Based

The objective of this work was to evaluate the effects of testosterone (T) and 17β-estradiol (E2) on coronary microvascular endothelial cells (CMECs) of male and female rats. To analyze the short-term effects of such sex steroid hormones on intracellular Ca2+ concentration ([Ca2+]i) kinetics, we used the chelating agent fura-2 acetoxymethyl ester. We also explored the possibility of testosterone aromatization by using selective inhibitors of the aromatase enzyme cytochrome P-450 aromatase ( P450arom), aminoglutethimide (4 μM), and 4-hydroxyandrostenedione (4 μM). The presence of P450arom was investigated by immunocytochemical and immunoblot assays using peptide-generated polyclonal antibodies raised against a 20-amino acid synthetic fragment of rat P450arom and by in situ hybridization to locate the aromatase mRNA in such cells. The activity of P450arom was demonstrated by the stereospecific loss of the tritium atom of [1β-3H]androstenedione. Our results indicate that both T and E2 induced a rapid increase in [Ca2+]i. The fact that the effects of E2 and T were carried out within milliseconds suggests that they were exerted at the membrane level and not through intracellular receptors. The possibility of involvement of PLC-β in these effects is suggested because U-73122 (a PLC inhibitor) blocked the effects of both T and E2. Immunocytochemical assays indicated the expression of androgenic and estrogenic receptors in these cells. The effects of T were blocked by the selective aromatase inhibitors. We also demonstrated membrane association of P450arom, expression of the ovary-specific mRNA after in situ hybridization, and E2 formation resulting from a significant activity of P450arom in CMECs. There were no gender-based differences.

Studies of the Factor Xa-Dependent Inhibitor of Factor VIIa/Tissue Factor (Extrinsic Pathway Inhibitor) from Cell Supernates of Cultured Human Umbilical Vein Endothelial Cells

1989 ◽  
Vol 61 (01) ◽  
pp. 101-105 ◽  
Author(s):  
Bonnie J Warn-Cramer ◽  
Fanny E Almus ◽  
Samuel I Rapaport
Keyword(s):  
Molecular Weight ◽  
Endothelial Cells ◽  
Tissue Factor ◽  
Phorbol Ester ◽  
Umbilical Vein ◽  
Primary Cultures ◽  
Factor Xa ◽  
Extrinsic Pathway ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

SummaryCultured human umbilical vein endothelial cells (HUVEC) have been reported to produce extrinsic pathway inhibitor (EPI), the factor Xa-dependent inhibitor of factor VHa/tissue factor (TF). We examined the release of this inhibitor from HUVEC as a function of their growth state and in response to the induction of endothelial cell TF activity. HUVEC constitutively produced significant amounts of EPI at all stages of their growth in culture including the post-confluent state. Rate of release varied over a 3-fold range for primary cultures from 12 different batches of pooled umbilical cord cells. Constitutive EPI release was unaltered during a 6 hour period of induction of TF activity with thrombin or phorbol ester but slowed during longer incubation of the cells with phorbol ester. Whereas plasma contains two molecular weight forms of EPI, only the higher of these two molecular weight forms was demonstrable by Western analysis of HUVEC supernatants with 125I-factor Xa as the ligand.

Specificity of the Thrombin-Induced Release of Tissue Plasminogen Activator from Cultured Human Endothelial Cells

1986 ◽  
Vol 56 (02) ◽  
pp. 115-119 ◽  
Author(s):  
Eugene G Levin ◽  
David M Stern ◽  
Peter P Nawroth ◽  
Richard A Marlar ◽  
Daryl S Fair ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Protein C ◽  
Primary Cultures ◽  
Activated Protein C ◽  
Specific Inhibitor ◽  
Factor Xa ◽  
Human Endothelial Cells ◽  
Tissue Plasminogen

SummaryThe addition of thrombin (9 nM) to primary cultures of human endothelial cells induces a 6- to 7-fold increase in the rate of release of tissue plasminogen activator (tPA). Several other serine proteases which specifically interact with endothelial cells were also analyzed for their effect on tPA release. Gamma-thrombin, an autocatalytic product of α-thrombin, promoted tPA release but was less effective than α-thrombin. A maximum increase of 5.5-fold was observed, although a concentration of γ-thrombin 20 times greater than α-thrombin was required. The response to Factor Xa was similar to α-thrombin, although the stimulation was significantly reduced by the addition of hirudin or DAPA suggesting that prothrombin activation was occurring. The simultaneous addition of prothrombin with Factor Xa resulted in enhanced tPA release equal to that observed with an equimolar concentration of active α-thrombin. Thus, under these conditions, Factor Xa-cell surface mediated activation of prothrombin can lead to a secondary effect resulting from cell-thrombin interaction. Activated protein C, which has been implicated as a profibrinolytic agent, was also tested. No change in tPA release occurred after the addition of up to 325 nM activated protein C in the presence or absence of proteins. Factor IXa and plasmin were also ineffective. The effect of thrombin on the endothelial cell derived plasminogen activator specific inhibitor was also studied. Thrombin produced a small but variable release of the inhibitor with an increase of less than twice that of non-thrombin treated controls.

Monosodium glutamate administration early in life alters pineal melatonin nocturnal profile in adulthood

2021 ◽  
Vol 4 (1) ◽  
pp. 99-114
Author(s):  
Janaína B Garcia ◽  
Fernanda G Do Amaral ◽  
Daniela C Buonfiglio ◽  
Rafaela FA Vendrame ◽  
Patrícia L Alves ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Pineal Gland ◽  
Serum Insulin ◽  
Monosodium Glutamate ◽  
Female Rats ◽  
Pineal Melatonin ◽  
Melatonin Synthesis ◽  
Male And Female Rats ◽  
Melatonin Production

The pineal gland synthesizes melatonin exclusively at night, which gives melatonin the characteristic of a temporal synchronizer of the physiological systems. Melatonin is a regulator of insulin activities centrally and also peripherally and its synthesis is reduced in diabetes.  Since monosodium glutamate (MSG) is often used to induce the type 2 diabetic and metabolic syndrome in animal models, the purpose of this work is to evaluate the potential effects of MSG given to neonates on the pineal melatonin synthesis in different aged male and female rats. Wistar rats were subcutaneously injected with MSG (4mg/g/day) or saline solution (0.9%) from the second to eighth post-natal day. The circadian profiles both melatonin levels and AANAT activity were monitored at different ages. Body weight, naso-anal length, adipose tissues weight, GTT, ITT and serum insulin levels were also evaluated. Typical obesity with the neonatal MSG treatment was observed, indicated by a great increase in adipose depots without a concurrent increase in body weight. MSG treatment did not cause hyperglycemia or glucose intolerance, but induced insulin resistance. An increase of melatonin synthesis at ZT 15 with phase advance was observed in in some animals. The AANAT activity was positively parallel to the melatonin circadian profile. It seems that MSG causes hypothalamic obesity which may increase AANAT activity and melatonin production in pineal gland. These effects were not temporally correlated with insulin resistance and hyperinsulinemia indicating the hypothalamic lesions, particularly in arcuate nucleus induced by MSG in early age, as the principal cause of the increase in melatonin production.

THE PITUITARY AND ADRENAL RESPONSES TO ADMINISTRATION OF OESTRIOL IN GONADECTOMIZED RATS

1961 ◽  
Vol 38 (1) ◽  
pp. 50-58 ◽  
Author(s):  
N. E. Borglin ◽  
L. Bjersing
Keyword(s):  
Pituitary Gland ◽  
Adrenal Cortex ◽  
Clinical Experience ◽  
Uterine Cervix ◽  
Morphological Changes ◽  
Physiological Significance ◽  
Female Rats ◽  
Experimental Conditions ◽  
Male And Female ◽  
Male And Female Rats

ABSTRACT Oestriol (oestra-1,3,5(10)-triene-3,16α,17β-triol) is a weakly oestrogenic substance which, however, in contrast to what was formerly believed, is of physiological significance. Its effect is localized largely to the uterine cervix and vagina. Clinical experience argues both for and against an effect on the pituitary gland. This investigation is concerned with the morphological changes in the pituitary gland and adrenal cortex of gonadectomized male and female rats after the injection of oestriol. It was found that oestriol has the same type of action on these glands as other oestrogens, but under the experimental conditions used, this effect proved much weaker than that produced by oestradiol (oestra-1,3,5(10)-triene-3,17β-diol).

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