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In vitro assessment of mouse fetal abdominal aortic vascular function.

ABSTRACT: Fetal growth restriction (FGR) affects 3-8% of human pregnancies. Mouse models have provided important etiological data on FGR; they permit the assessment of treatment strategies on the physiological function of both mother and her developing offspring. Our study aimed to 1) develop a method to assess vascular function in fetal mice and 2) as a proof of principle ascertain whether a high dose of sildenafil citrate (SC; Viagra) administered to the pregnant dam affected fetal vascular reactivity. We developed a wire myography methodology for evaluation of fetal vascular function in vitro using the placenta-specific insulin-like growth factor II (Igf2) knockout mouse (P0; a model of FGR). Vascular function was determined in abdominal aortas isolated from P0 and wild-type (WT) fetuses at embryonic day (E) 18.5 of gestation. A subset of dams received SC 0.8 mg/ml via drinking water from E12.5; data were compared with water-only controls. Using wire myography, we found that fetal aortic rings exhibited significant agonist-induced contraction, and endothelium-dependent and endothelium-independent relaxation. Sex-specific alterations in reactivity were noted in both strains. Maternal treatment with SC significantly attenuated endothelium-dependent and endothelium-independent relaxation of fetal aortic rings. Mouse fetal abdominal aortas reproducibly respond to vasoactive agents. Study of these vessels in mouse genetic models of pregnancy complications may 1) help to delineate early signs of abnormal vascular reactivity and 2) inform whether treatments given to the mother during pregnancy may impact upon fetal vascular function.

SUBMITTER: Renshall LJ

PROVIDER: S-EPMC4166756 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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In vitro assessment of mouse fetal abdominal aortic vascular function.

Renshall Lewis J LJ Dilworth Mark R MR Greenwood Susan L SL Sibley Colin P CP Wareing Mark M

American journal of physiology. Regulatory, integrative and comparative physiology 20140723 6

Fetal growth restriction (FGR) affects 3-8% of human pregnancies. Mouse models have provided important etiological data on FGR; they permit the assessment of treatment strategies on the physiological function of both mother and her developing offspring. Our study aimed to 1) develop a method to assess vascular function in fetal mice and 2) as a proof of principle ascertain whether a high dose of sildenafil citrate (SC; Viagra) administered to the pregnant dam affected fetal vascular reactivity. ...[more]

PMID: 25056105

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Project description:BackgroundEndovascular aortic repair (EVAR) is obviously less invasive than open aortic repair (OAR) for the treatment of infra-renal abdominal aortic aneurysm (AAA). However, it is not free of complications which can potentially result in severe morbidity or even mortality. The purpose of this study was to share our single-center experience with stent-graft related and systemic complications associated with EVAR.MethodsPatients with infra-renal AAA treated by elective and emergency EVAR between March 2014 and November 2020 were retrospectively identified. Demographic data, risk factors, American Society of Anesthesiologists (ASA) score, systemic complications, stent-graft related complications, surgical site complications, 30-day mortality, late EVAR related mortality, estimated blood loss, intensive care unit (ICU) length of stay (LOS), hospital LOS and follow-up durations were collected and analyzed.ResultsA total of 43 patients underwent EVAR during the period of study. There were 42 males (97.7%) and 1 female (2.3%). The mean age was 68.8 ± 6.2 years. Elective EVAR was performed in 36 (83.7%) and emergency EVAR in 7 (16.3%). Technical success was achieved in 42 patients (100%) with no conversion to OAR. Stent-graft related complications were (21.0%) endoleaks, (2.3%) graft limb occlusion, (0%) graft infection, and (2.3%) rupture-EVAR. Systemic complications were (2.3%) myocardial infarction (MI), (2.3%) stroke, (2.3%) spinal cord injury (SCI), (2.3%) respiratory failure, (19.0%) wound complications, and (2.3%) acute lower limb ischemia (ALI). The 30-day mortality was (2.3%) due to perioperative MI and the late graft related mortality was (2.3%) due to rupture-EVAR.ConclusionEVAR showed a high technical success rate with no conversion to OAR. The most common complications were type II and type I endoleaks followed by graft limb occlusion. The 30-day mortality was 2.3% due to perioperative MI. Only one late stent-graft related mortality was registered due to rupture-EVAR.

Project description:BackgroundAbdominal aortic aneurysm (AAA), a degenerative vascular pathology characterized by permanent dilation of the aorta, is considered a chronic inflammatory disease involving innate/adaptive immunity. However, the functional role of antibody-dependent immune response against antigens present in the damaged vessel remains unresolved. We hypothesized that engagement of immunoglobulin G (IgG) Fc receptors (FcγR) by immune complexes (IC) in the aortic wall contributes to AAA development. We therefore evaluated FcγR expression in AAA lesions and analysed whether inhibition of FcγR signaling molecules (γ-chain and Syk kinase) influences AAA formation in mice.MethodsFcγR gene/protein expression was assessed in human and mouse AAA tissues. Experimental AAA was induced by aortic elastase perfusion in wild-type (WT) mice and γ-chain knockout (γKO) mice (devoid of activating FcγR) in combination with macrophage adoptive transfer or Syk inhibitor treatment. To verify the mechanisms of FcγR in vitro, vascular smooth muscle cells (VSMC) and macrophages were stimulated with IgG IC.ResultsFcγR overexpression was detected in adventitia and media layers of human and mouse AAA. Elastase-perfused γKO mice exhibited a decrease in AAA incidence, aortic dilation, elastin degradation, and VSMC loss. This was associated with (1) reduced infiltrating leukocytes and immune deposits in AAA lesions, (2) inflammatory genes and metalloproteinases downregulation, (3) redox balance restoration, and (4) converse phenotype of anti-inflammatory macrophage M2 and contractile VSMC. Adoptive transfer of FcγR-expressing macrophages aggravated aneurysm in γKO mice. In vitro, FcγR deficiency attenuated inflammatory gene expression, oxidative stress, and phenotypic switch triggered by IC. Additionally, Syk inhibition prevented IC-mediated cell responses, reduced inflammation, and mitigated AAA formation.ConclusionOur findings provide insight into the role and mechanisms mediating IgG-FcγR-associated inflammation and aortic wall injury in AAA, which might represent therapeutic targets against AAA disease.

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In vitro assessment of mouse fetal abdominal aortic vascular function.

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In vitro assessment of mouse fetal abdominal aortic vascular function.

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