Canadian journal of physiology and pharmacology
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Can. J. Physiol. Pharmacol. · Mar 2019
ReviewThe role of aspirin and inflammation on reproduction: the EAGeR trial 1.
Inflammation has been linked to several complications in pregnancy, including pregnancy loss. Due to its anti-inflammatory properties, aspirin, a widely available and inexpensive therapy, has potential to help mitigate the negative effects of inflammation along the reproductive pathway. Therefore, the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial was designed to elucidate whether preconception-initiated daily low-dose aspirin would increase the live birth rate in women with 1-2 prior pregnancy losses and no infertility diagnosis and attempting unassisted conception. ⋯ When stratified by tertile of C-reactive protein (CRP), a biomarker of inflammation, treatment with aspirin restored a decrement in the live birth rate in women in the highest CRP tertile (relative risk 1.35, 95% confidence interval 1.08-1.67), increasing to similar rates as women of the lower and mid-CRP tertiles. The same effect modification by inflammation status was observed when examining the effect of low-dose aspirin on offspring sex ratio. These results suggest that inflammation plays an important role in reproduction, and that chronic, low-grade inflammation may be amenable to aspirin treatment.
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Can. J. Physiol. Pharmacol. · Sep 2018
Upregulated long noncoding RNA Snhg1 promotes the angiogenesis of brain microvascular endothelial cells after oxygen-glucose deprivation treatment by targeting miR-199a.
Angiogenesis after ischemic stroke has important clinical significance, which stimulates endogenous recovery mechanisms and improves the neurological outcome. Enhancing angiogenesis may facilitate the function recovery from ischemic stroke. Recent studies have shown that aberrant expression of long noncoding RNAs (lncRNAs) is related to angiogenesis after ischemic stroke. ⋯ Oxygen-glucose deprivation/reoxygenation (OGD/R) was used to mimic ischemia/reperfusion injury in vitro. Sngh1 was increased in brain microvascular endothelial cells (BMECs) with the prolongation of exposure to OGD, and promoted BMEC survival under OGD/R condition, and angiogenesis after OGD/R treatment. miR-199a was identified and validated to be a direct target of Snhg1, and function effects of Snhg1 on BMEC survival and angiogenesis depended on miR-199a, which is involved in the regulation of hypoxia inducible factor and vascular endothelial cell growth factor expression. These findings contribute to a better understanding of the pathogenesis of ischemic stroke and facilitate the development of proangiogenesis therapy for this disease.
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Can. J. Physiol. Pharmacol. · Aug 2018
Differential participation of calcium-activated potassium channel in endothelium-dependent hyperpolarization-type relaxation in superior mesenteric arteries of spontaneously hypertensive rats.
The purpose of this study was to determine the relationship of KCa channels to endothelium-dependent hyperpolarizing factor (EDHF)-mediated relaxation induced by acetylcholine (ACh) in the superior mesenteric arteries of 7-month-old spontaneously hypertensive rats (SHR). Upon inhibition of nitric oxide synthase and cyclooxygenase, ACh-induced EDHF-mediated relaxation was found to be weaker in SHR than in age-matched Wistar Kyoto rats (WKY). These relaxations in both group were attenuated by combined treatment with small-conductance and intermediate-conductance Ca2+-activated K+ channels (SKCa and IKCa) inhibitors, with the exception of relaxation resistant to inhibition of these channels in SHR (vs. ⋯ Protein expression of IKCa and SKCa in the arteries did not differ between the 2 groups, whereas ratio of sloβ1 subunit to α subunit of BKCa was increased in SHR (vs. WKY). These results suggest that EDHF-mediated relaxations in superior mesenteric arteries are impaired in SHR, and utilize components of BKCa in addition to SKCa/IKCa channel activities, that the increased participation of BKCa may be attributable to alterations in α and sloβ1 subunit ratio, and that components unrelated to KCa activity may also contribute to the difference between SHR and WKY arteries.
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Can. J. Physiol. Pharmacol. · Apr 2017
Anti-inflammatory effects of pelargonidin on TGFBIp-induced responses.
Transforming growth factor β induced protein (TGFBIp) is an extracellular matrix protein expressed in several cell types in response to TGF-β. TGFBIp is released by human umbilical vein endothelial cells (HUVECs) and functions as a mediator of experimental sepsis. Pelargonidin (PEL) is a well-known red pigment found in plants, and has been reported as having important biological activities that are potentially beneficial for human health. ⋯ We found that PEL inhibited TGFBIp-induced barrier disruption, expression of cell adhesion molecules and adhesion/transendothelial migration of neutrophils to human endothelial cells. PEL also suppressed TGFBIp-induced hyperpermeability and leukocyte migration in vivo. These results suggest that PEL possesses anti-inflammatory properties that result in inhibition of hyperpermeability, expression of cell adhesion molecules, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases.
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Cannabis sativa has long been used for medicinal purposes. To improve safety and efficacy, compounds from C. sativa were purified or synthesized and named under an umbrella group as cannabinoids. Currently, several cannabinoids may be prescribed in Canada for a variety of indications such as nausea and pain. ⋯ The therapeutic potential of cannabinoids is therefore extended; however, evidence is limited and mechanisms remain unclear. In addition, the use of cannabinoids clinically has been hindered due to pronounced psychoactive side effects. This review provides an overview on the endocannabinoid system, including known physiological roles, and conditions in which cannabinoid receptor signaling has been implicated.