The role of sex steroids on cellular events involved in vascular disease

Cutini, P.; Campelo, Adrián Esteban; Agriello, Evangelina; Sandoval, Marisa Julia; Rauschemberger, María Belén; Massheimer, Virginia

doi:10.1016/j.jsbmb.2012.08.001

Cited by 27 publications

(17 citation statements)

References 31 publications

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“…45 We assume that with the enhanced CAM expression on ECs, the likelihood of circulating leukocytes to interact with the activated endothelium greatly increases. We should acknowledge however that in addition to stretch, soluble factors (e.g., complement 48 ) and sex steroids 49 that have been shown to modulate CAM expression also likely contribute to the increase in immune cell invasion near term.…”

Section: Discussionmentioning

confidence: 99%

Stretch-induced human myometrial cytokines enhance immune cell recruitment via endothelial activation

2014

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Spontaneous term labour is associated with amplified inflammatory events in the myometrium including cytokine production and leukocyte infiltration; however, potential mechanisms regulating such events are not fully understood. We hypothesized that mechanical stretch of the uterine wall by the growing fetus facilitates peripheral leukocyte extravasation into the term myometrium through the release of various cytokines by uterine myocytes. Human myometrial cells (hTERT-HM) were subjected to static mechanical stretch; stretch-conditioned media was collected and analysed using 48-plex Luminex assay and ELISA. Effect of stretch-conditioned media on cell adhesion molecule expression of human uterine microvascular endothelial cells (UtMVEC-Myo) was detected by quantitative polymerase chain reaction (qPCR) and flow cytometry; functional assays testing leukocyte-endothelial interactions: adhesion of leukocytes to endothelial cells and transendothelial migration of calcein-labelled primary human neutrophils as well as migration of THP-1 monocytic cells were assessed by fluorometry. The current in vitro study demonstrated that mechanical stretch (i) directly induces secretion of multiple cytokines and chemokines by hTERT-HM cells (IL-6, CXCL8, CXCL1, migration inhibitory factor (MIF), VEGF, G-CSF, IL-12p70, bFGF and platelet-derived growth factor subunit B (PDGF-bb), P,0.05); stretch-induced cytokines (ii) enhance leukocyte adhesion to the endothelium of the surrounding uterine microvasculature by (iii) inducing the expression of endothelial cell adhesion molecules and (iv) directing the transendothelial migration of peripheral leukocytes. (vi) Chemokine-neutralizing antibodies and broad-spectrum chemokine inhibitor block leukocyte migration. Our data provide a proof of mechanical regulation for leukocyte recruitment from the uterine blood vessels to the myometrium, suggesting a putative mechanism for the leukocyte infiltrate into the uterus during labour and postpartum involution.

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Section: Discussionmentioning

confidence: 99%

Stretch-induced human myometrial cytokines enhance immune cell recruitment via endothelial activation

2014

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“…Likewise, the beneficial effect of androgens on the vascular function of males is widely recognized [5], [29]–[31]. The effects of androgenic derivatives on NO [12], [13] and prostanoids [32], [33] signalling pathways in different tissues have been described.…”

Section: Discussionmentioning

confidence: 99%

Time-Dependent Effect of Orchidectomy on Vascular Nitric Oxide and Thromboxane A2 Release. Functional Implications to Control Cell Proliferation through Activation of the Epidermal Growth Factor Receptor

et al. 2014

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This study analyzes whether the release of nitric oxide (NO) and thromboxane A2 (TXA2) depends on the time lapsed since gonadal function is lost, and their correlation with the proliferation of vascular smooth muscle cells (VSMC) mediated by the epidermal growth factor receptor (EGFR). For this purpose, aortic and mesenteric artery segments from control and 6-weeks or 5-months orchidectomized rats were used to measure NO and TXA2 release. The results showed that the basal and acetylcholine (ACh)-induced NO release were decreased 6 weeks post-orchidectomy both in aorta and mesenteric artery, but were recovered 5 months thereafter up to levels similar to those found in arteries from control rats. The basal and ACh-induced TXA2 release increased in aorta and mesenteric artery 6 weeks post-orchidectomy, and was maintained at high levels 5 months thereafter. Since we previously observed that orchidectomy, which decreased testosterone level, enlarged the muscular layer of mesenteric arteries, the effect of testosterone on VSMC proliferation was analyzed. The results showed that treatment of cultured VSMC with testosterone downregulated mitogenic signaling pathways initiated by the ligand-dependent activation of the EGFR. In contrast, the EGFR pathways were constitutively active in mesenteric arteries of long-term orchidectomized rats. Thus, the exposure of mesenteric arteries from control rats to epidermal growth factor (EGF) induced the activation of EGFR signaling pathways. However, the addition of EGF to arteries from orchidectomized rats failed to induce a further activation of these pathways. In conclusion, this study shows that the release of NO depends on the time lapsed since the gonadal function is lost, while the release of TXA2 is already increased after short periods post-orchidectomy. The alterations in these signaling molecules could contribute to the constitutive activation of the EGFR and its downstream signaling pathways after long period post-orchidectomy enhancing the proliferation of the vascular muscular layer.

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“…However, they showed that the presence of T depressed further platelet aggregation. What Campelo et al [18] and Cutini et al [19] had reported that T has anti-aggregatory action is contrary to what Rosenblum et al [15], Matsuda et al [16], and Ajayi and Haluskha [17] had proved that T has proaggregatory action. The difference is the result of the design of the experiment.…”

Section: Platelet Aggregation Testmentioning

confidence: 87%

“…Campelo et al [18] and Cutini et al [19] offered another approach by incubating monolayer EC from rat aortic rings with PRP and T at various doses. After 1-minute incubation, PRP was removed from the plate and measured platelets aggregation by turbidimetric method using 5 µM of ADP as platelet agonist.…”

Section: Platelet Aggregation Testmentioning

confidence: 99%

“…The difference is the result of the design of the experiment. Campelo et al [16] and Cutini et al [19] applied T to EC and platelet at the same time, whereas Rosenblum et al [15], Matsuda et al [16], and Ajayi and Haluskha [17] were more focus to the exposure of T to platelet. Indeed, Khetawat et al [20] showed that androgen receptors were detected in platelet.…”

Section: Platelet Aggregation Testmentioning

confidence: 99%

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High Glucose, but Not Testosterone, Increases Platelet Aggregation Mediated by Endothelial Cells

Jenie¹,

Mulyono²,

Aswin³

et al. 2015

IJPHS

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Endothelial cells inhibit platelet aggregation by releasing thromboregulators, such as prostacyclin and nitric oxide. Male subject is a traditional risk factor for cardiovascular diseases. Platelet hyperreactivity has been frequently found in patient with diabetes mellitus. To examine whether testosterone and high glucose modify platelet aggregation through endothelial cells, we did an in vitro study using endothelial cells culture from human umbilical vein (HUVEC). Treatments were performed in HUVEC sub culture as either normoglucose (5.6 mM) or high glucose (22.4 mM) medium, with or without testosterone (0, 1, 10, 100 nM), for 24 hours. HUVEC were trypsinized, resuspended, and then incubated with platelet rich plasma from healthy male donors with ratio 1:10 4 for 3 minutes. Platelet aggregation measured by turbidimetry methode. This study showed that testosterone did not significantly influence platelet aggregation through endothelial cells in normoglucose (p = 0.144) or high glucose (p = 0.916) medium. There was no main effect of testosterone (p = 0.73) as well as no interaction between testosterone and glucose (p = 0.69), but there was a main effect of glucose (p = 0.004), to platelet aggregation through endothelial cells. In conclusion, high glucose, but not testosterone, inhibits platelet aggregation mediated by endothelial cells.

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The role of sex steroids on cellular events involved in vascular disease

Cited by 27 publications

References 31 publications

Stretch-induced human myometrial cytokines enhance immune cell recruitment via endothelial activation

Stretch-induced human myometrial cytokines enhance immune cell recruitment via endothelial activation

Time-Dependent Effect of Orchidectomy on Vascular Nitric Oxide and Thromboxane A2 Release. Functional Implications to Control Cell Proliferation through Activation of the Epidermal Growth Factor Receptor

High Glucose, but Not Testosterone, Increases Platelet Aggregation Mediated by Endothelial Cells

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