scholarly journals Diabetes and the maternal resistance vasculature

2001 ◽  
Vol 101 (6) ◽  
pp. 719-729 ◽  
Author(s):  
Christine ANG ◽  
Mary Ann LUMSDEN
Keyword(s):  
Blood Flow ◽  
Vascular Endothelium ◽  
Pregnancy Outcomes ◽  
Vascular Function ◽  
Vascular Reactivity ◽  
Vascular Dysfunction ◽  
Tissue Perfusion ◽  
Endocrine Disorder ◽  
Patient Morbidity ◽  
Adverse Pregnancy

Diabetes is the most common endocrine disorder worldwide, with complications that include the development of both macro- and micro-vascular disease that contribute significantly to patient morbidity and mortality. The severity of diabetic complications is amplified during pregnancy, resulting in a higher incidence of adverse pregnancy outcomes such as pre-eclampsia, placental insufficiency and stillbirth than in non-diabetics. Vascular dysfunction is thought to underlie many of these complications, with the greatest impact occurring at the level of the resistance vasculature, where alterations in vascular reactivity can significantly affect blood flow and tissue perfusion. It is likely that problems associated with diabetic pregnancies are related, in part, to abnormal vascular function, particularly dysfunction of the vascular endothelium.

scholarly journals Differential involvement of COX1 and COX2 in the vasculopathy associated with the α-galactosidase A-knockout mouse

2009 ◽  
Vol 296 (4) ◽  
pp. H1133-H1140 ◽  
Author(s):  
James L. Park ◽  
Liming Shu ◽  
James A. Shayman
Keyword(s):  
Endothelial Dysfunction ◽  
Fabry Disease ◽  
Vascular Endothelium ◽  
Vascular Function ◽  
Knockout Mouse ◽  
Vascular Reactivity ◽  
Lysosomal Storage ◽  
Wild Type ◽  
Cox Inhibitors ◽  
Differential Involvement

The lysosomal storage disorder Fabry disease is characterized by excessive globotriaosylceramide (Gb3) accumulation in major organs such as the heart and kidney. Defective lysosomal α-galactosidase A (Gla) is responsible for excessive Gb3 accumulation, and one cell sensitive to the effects of Gb3 accumulation is vascular endothelium. Endothelial dysfunction is associated with Fabry disease and excessive cellular Gb3. We previously demonstrated that excessive vascular Gb3 in a mouse model of Fabry disease, the Gla-knockout ( Gla−/0) mouse, results in abnormal vascular function, which includes abnormal endothelium-dependent contractions, a vascular phenomenon known to involve cyclooxygenase (COX). Therefore, we hypothesized that the vasculopathy in the Gla knockout mouse may be due to a vasoactive COX-derived product. To test this hypothesis, vascular reactivity experiments were performed in aortic rings from wild-type ( Gla+/0) and Gla−/0 mice in the presence and absence of specific and nonspecific COX inhibitors. Specific inhibition of COX1 or COX2 in endothelium-intact rings from Gla−/0 mice decreased overall phenylephrine contractility compared with untreated Gla−/0 rings, whereas COX inhibitors had no effect on contractility in endothelium-denuded rings. Nonspecific inhibition of COX with indomethacin (10 μmol/l) or COX1 inhibition with valeryl salicylate (3 mmol/l) improved endothelial function in rings from Gla−/0 mice, but COX2 inhibition with NS-398 (1 μmol/l) further increased endothelial dysfunction in rings from Gla−/0 mice. These results suggest that, in the Gla−/0 mice, COX1 and COX2 activity are increased and localized in the endothelium, producing vasopressor and vasorelaxant products, which contribute to the Fabry-related vasculopathy.

Abstract P217: Nox Compartmentalization, Protein Oxidation and ER Stress in Vascular Smooth Muscle Cells in Hypertension

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Livia L Camargo ◽  
Augusto C Montezano ◽  
Adam Harvey ◽  
Sofia Tsiropoulou ◽  
Katie Hood ◽  
...  
Keyword(s):  
Er Stress ◽  
Protein Oxidation ◽  
Vascular Function ◽  
Vascular Reactivity ◽  
Stress Proteins ◽  
Vascular Dysfunction ◽  
Mesenteric Arteries ◽  
Resistance Arteries ◽  
Post Translational Modification ◽  
Wistar Kyoto

In hypertension, activation of NADPH oxidases (Noxs) is associated with oxidative stress and vascular dysfunction. The exact role of each isoform in hypertension-associated vascular injury is still unclear. We investigated the compartmentalization of Noxs in VSMC from resistance arteries of Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). Expression of Nox1 and Nox4 was increased in SHR cells (96.6±28.7% and 48.2±21.2% vs WKY, p<0.05), as well as basal ROS levels measured by chemiluminescence (110.2±26.4% vs WKY, p<0.05) and amplex red (105.2±33.2% vs WKY, p<0.05). Phosphorylation of unfolded protein response activators, PERK and IRE1α, and expression of ER chaperone BiP were elevated in SHR cells (p<0.05 vs WKY), indicating activation of ER stress response. Immunoblotting after organelle fractionation demonstrated that Noxs are expressed in an organelle-specific manner, with Nox1, 2 and 4 present in plasma membrane, ER and nucleus, but not in mitochondria. In SHR cells, NoxA1ds (Nox1 inhibitor, 10μM) and GKT136901 (Nox1/4 inhibitor, 10μM) decreased AngII-induced ROS levels (p<0.001 vs Ctl). Additionally, mito-tempol (mitochondrial-targeted antioxidant, 50nM) and 4-PBA (ER stress inhibitor, 1mM) decreased basal ROS levels in SHR cells (p<0.05 vs Ctl). Furthermore, oxidation of the antioxidant enzymes Peroxiredoxins (Prx) was increased in SHRSP compared to WKY (2.51±0.14 vs 0.56±0.07, p<0.001). One-dimensional isoelectric focusing revealed that cytosolic Prx2 and mitochondrial Prx3 were more oxidized in SHRSP than WKY cells. Using a biotin-tagged dimedone-based probe (DCP-Bio) we identified oxidation of ER stress proteins BiP and IRE1. To investigate the effect of protein oxidation in vascular function, vascular reactivity was evaluated in isolated mesenteric arteries. Inhibition of general oxidation (DTT 1mM; Emax: 111.7±33.1) and peroxiredoxin (Conoidin A 10nM; Emax: 116.0±7.3) reduces vascular contraction in response to noradrenalin in WKY rats (Emax: 166.6±30.2; p<0.05). These findings suggest an important role for Nox1/4 in redox-dependent organelle dysfunction and post-translational modification of proteins, processes that may play an important role in vascular dysfunction in hypertension.

Abstract 14820: Sirt7 Deficiency in Blood Vessel Components Impairs Vascular Function by Inhibiting Cell Cycle- and Inflammatory-Related Protein Expression

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Yuichi Kimura ◽  
Yasuhiro Izumiya ◽  
Satoshi Araki ◽  
Satoru Yamamura ◽  
Yoshiro Onoue ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Blood Flow ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Vascular Diseases ◽  
Tube Formation ◽  
Hindlimb Ischemia ◽  
Proliferation Assay

Introduction: Aging is a well-established cardiovascular risk factor and associated with vascular dysfunction. Sirt7, one of the members of mammalian sirtuin family, is thought to be involved in age-related diseases. However, little is known about the relative contribution of Sirt7 in vascular dysfunction. Hypothesis: Sirt7 maintains vascular cell functions and its deficiency plays a critical role in vascular diseases. Methods: Sirt7 loss- and gain-of-function experiments were performed with human aortic smooth muscle cells (HAoSMCs) and human umbilical vein endothelial cells (HUVECs). In vivo, blood flow recovery was evaluated by hindlimb ischemia model in homozygous Sirt7 deficient (Sirt7-/-) and wild-type (WT) mice. Irradiated WT mice were intravenously received bone marrow (BM) cells from WT or Sirt7 -/- mouse to achieve BM transfer. Results: An RNAi-medicated Sirt7 knockdown resulted in a significant inhibition of HAoSMCs proliferation following serum or Platelet-derived growth factor BB (PDGF-BB) stimulation as determined by cell count, BrdU cell proliferation assay and MTS proliferation assay. Knockdown of endogenous Sirt7 also reduced cell migration as revealed by Boyden chamber migration assay. The Cyclin D1 and Cyclin dependent kinase 2 (CDK2) protein levels were significantly decreased in Sirt7 siRNA-treated HAoSMCs in response to serum or PDGF-BB stimulation. In endothelial cells, knockdown of Sirt7 attenuated tube formation, proliferation and migration. These changes were accompanied by reduced ERK activation and VCAM-1 mRNA and protein expression in Sirt7 siRNA-treated HUVECs. Conversely, overexpression of Sirt7 by adenovirus enhanced tube formation and cell proliferation. In vivo, blood flow recovery in response to hindlimb ischemia was significantly attenuated in Sirt7-/- mice compared with WT mice. There was no difference in blood flow recovery between WT mice transplanted with WT or Sirt7-/- BM cells suggesting that Sirt7 deficiency in vascular cells have a predominant effect on attenuated blood flow recovery in response to hindlimb ischemia. Conclusions: Sirt7 in blood vessel components have an important role in maintenance of vascular function. Sirt7 could be a promising therapeutic target for vascular diseases.

Endothelin-mediated in vivo pressor responses following TRPV1 activation

2011 ◽  
Vol 301 (3) ◽  
pp. H1135-H1142 ◽  
Author(s):  
Vahagn A. Ohanyan ◽  
Giacinta Guarini ◽  
Charles K. Thodeti ◽  
Phani K. Talasila ◽  
Priya Raman ◽  
...  
Keyword(s):  
Vascular Function ◽  
Vascular Reactivity ◽  
Transient Receptor Potential ◽  
Vascular Dysfunction ◽  
Vascular Complications ◽  
Receptor Potential ◽  
Immunoblot Analysis ◽  
Trpv1 Channels ◽  
Transient Receptor

Transient receptor potential vanilliod 1 (TRPV1) channels have recently been postulated to play a role in the vascular complications/consequences associated with diabetes despite the fact that the mechanisms through which TRPV1 regulates vascular function are not fully known. Accordingly, our goal was to define the mechanisms by which TRPV1 channels modulate vascular function and contribute to vascular dysfunction in diabetes. We subjected mice lacking TRPV1 [TRPV1(−/−)], db/ db, and control C57BLKS/J mice to in vivo infusion of the TRPV1 agonist capsaicin or the α-adrenergic agonist phenylephrine (PE) to examine the integrated circulatory actions of TRPV1. Capsaicin (1, 10, 20, and 100 μg/kg) dose dependently increased MAP in control mice (5.7 ± 1.6, 11.7 ± 2.1, 25.4 ± 3.4, and 51.6 ± 3.9%), which was attenuated in db/db mice (3.4 ± 2.1, 3.9 ± 2.1, 7.0 ± 3.3, and 17.9 ± 6.2%). TRPV1(−/−) mice exhibited no changes in MAP in response to capsaicin, suggesting the actions of this agonist are specific to TRPV1 activation. Immunoblot analysis revealed decreased aortic TRPV1 protein expression in db/db compared with control mice. Capsaicin-induced responses were recorded following inhibition of endothelin A and B receptors (ETA /ETB). Inhibition of ETA receptors abolished the capsaicin-mediated increases in MAP. Combined antagonism of ETA and ETB receptors did not further inhibit the capsaicin response. Cultured endothelial cell exposure to capsaicin increased endothelin production as shown by an endothelin ELISA assay, which was attenuated by inhibition of TRPV1 or endothelin-converting enzyme. TRPV1 channels contribute to the regulation of vascular reactivity and MAP via production of endothelin and subsequent activation of vascular ETA receptors. Impairment of TRPV1 channel function may contribute to vascular dysfunction in diabetes.

scholarly journals Delineating the age-related attenuation of vascular function: Evidence supporting the efficacy of the single passive leg movement as a screening tool

2019 ◽  
Vol 126 (6) ◽  
pp. 1525-1532 ◽  
Author(s):  
Jay R. Hydren ◽  
Ryan M. Broxterman ◽  
Joel D. Trinity ◽  
Jayson R. Gifford ◽  
Oh Sung Kwon ◽  
...  
Keyword(s):  
Blood Flow ◽  
Vascular Function ◽  
Screening Test ◽  
Vascular Dysfunction ◽  
Peripheral Vascular ◽  
Leg Blood Flow ◽  
Age Related ◽  
Cut Score ◽  
Leg Movement ◽  
Hyperemic Response

Continuous passive leg movement (PLM) is a promising clinical assessment of the age-related decline in peripheral vascular function. To further refine PLM, this study evaluated the efficacy of a single PLM (sPLM), a simplified variant of the more established continuous movement approach, to delineate between healthy young and old men based on vascular function. Twelve young (26 ± 5 yr) and 12 old (70 ± 7 yr) subjects underwent sPLM (a single passive flexion and extension of the knee joint through 90°), with leg blood flow (LBF, common femoral artery with Doppler ultrasound), blood pressure (finger photoplethysmography), and leg vascular conductance (LVC) assessed. A receiver operator characteristic curve analysis was used to determine an age-specific cut score, and a factor analysis was performed to assess covariance. Baseline LBF and LVC were not different between groups ( P = 0.6). The high level of covariance and similar predictive value for all PLM-induced LBF and LVC responses indicates LBF, alone, can act as a surrogate variable in this paradigm. The peak sPLM-induced increase in LBF from baseline was attenuated in the old (Young: 717 ± 227, Old: 260 ± 97 ml/min, P < 0.001; cut score: 372 ml/min), as was the total LBF response (Young: 155 ± 67, Old: 26 ± 17 ml, P < 0.001; cut score: 58 ml). sPLM, a simplified version of PLM, exhibits the prerequisite qualities of a valid screening test for peripheral vascular dysfunction, as evidenced by an age-related attenuation in the peripheral hyperemic response and a clearly delineated age-specific cut score. NEW & NOTEWORTHY Single passive leg movement (sPLM) exhibits the prerequisite qualities of a valid screening test for peripheral vascular dysfunction. sPLM displayed an age-related reduction in the peripheral hemodynamic response for amplitude, duration, initial rate of change, and total change with clearly delineated age-specific cut scores. sPLM has a strong candidate variable that is a simple single numeric value, for which to appraise peripheral vascular function, the 45-s hyperemic response (leg blood flow area under the curve: 45 s).

scholarly journals Endometrium and polycystic ovary syndrome

2018 ◽  
Vol 67 (4) ◽  
pp. 60-66
Author(s):  
Pavel P Yakovlev ◽  
Igor Yu Kogan
Keyword(s):  
Endometrial Cancer ◽  
Polycystic Ovary Syndrome ◽  
Pregnancy Outcomes ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Women Of Reproductive Age ◽  
Ovary Syndrome ◽  
Endocrine Disorder ◽  
Increased Risk ◽  
Adverse Pregnancy

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Patients with PCOS present with several endometrial abnormalities possibly explaining some of the adverse endometrium-related outcomes in these women. PCOS is inconsistently associated adverse pregnancy outcomes and an increased risk of endometrial cancer. The purpose of this review is to systematize the available data on endometrial dysfunction associated with PCOS. (For citation: Yakovlev PP, Kogan IYu. Endometrium and polycystic ovary syndrome. Journal of Obstetrics and Women’s Diseases. 2018;67(4):60-66. doi: 10.17816/JOWD67460-66).

scholarly journals Plasma cytokine response during the postprandial period: a potential causal process in vascular disease?

2005 ◽  
Vol 93 (1) ◽  
pp. 3-9 ◽  
Author(s):  
Graham C. Burdge ◽  
Philip C. Calder
Keyword(s):  
Inflammatory Cytokines ◽  
Vascular Endothelium ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Causal Mechanism ◽  
Causal Process ◽  
Fatty Meal ◽  
Postprandial Lipaemia ◽  
Soluble Adhesion Molecules ◽  
Pro Inflammatory Cytokines

Chronic inflammation of the vascular endothelium produces endothelial dysfunction and ultimately atherogenesis. Postprandial hyperlipidaemia is an independent risk factor for cardiovascular disease. Recent studies show that the magnitude of postprandial lipaemia following a single fatty meal is negatively related to vascular function. This is associated with a transient increase in the concentrations of pro-inflammatory cytokines and soluble adhesion molecules and in pro-oxidant activity. One possible interpretation is that repeated exposure of the blood vessel wall to the activities of pro-inflammatory cytokines and pro-oxidants may damage the vascular endothelium and promote atherogenesis. Based on these results, we propose a model of a causal mechanism to explain how consumption of a fatty meal may impair vascular dysfunction.

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