Early Disturbed Placental Ischemia and Hypoxia Creates Immune Alteration and Vascular Disorder Causing Preeclampsia

Kaposi's sarcoma (KS) is a neoplastic vascular disorder, classically arising in the skin of the lower extremities. As a consequence of the acquired immunodeficiency syndrome (AIDS) epidemic, an increasing number of patients have been found to have KS. In AIDS patients, KS appears to exhibit a more diffuse nature and frequently affects the head and neck. Mucosal lesions are most often seen, commonly involving the oral cavity. Only rare cases of laryngeal involvement have been recorded in the literature. We report 2 cases of KS of the supraglottic larynx. Our first patient, an elderly man of Mediterranean descent, complained of voice change and throat discomfort. Endoscopy with biopsy for diagnosis allowed conservative treatment with chemotherapy. Our second patient was a younger man with AIDS who presented with symptoms of airway obstruction. Management with carbon dioxide laser epiglottectomy was successful in relieving that patient's symptoms. Although rare, KS may present in both healthy and immunocompromised patients, and must be considered in the differential diagnosis of all violaceous lesions of the larynx.

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Exercise Training Attenuates Placental Ischemia-Induced Hypertension and Angiogenic Imbalance in the Rat

Hypertension ◽

10.1161/hypertensionaha.112.202275 ◽

2012 ◽

Vol 60 (6) ◽

pp. 1545-1551 ◽

Cited By ~ 26

Author(s):

Jeffrey S. Gilbert ◽

Christopher T. Banek ◽

Ashley J. Bauer ◽

Anne Gingery ◽

Karen Needham

Keyword(s):

Exercise Training ◽

Induced Hypertension ◽

Placental Ischemia

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Impact of hyperleptinemia during placental ischemia-induced hypertension in pregnant rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00724.2019 ◽

2021 ◽

Author(s):

Ana C. Palei ◽

Hunter L. Martin ◽

Barbara A. Wilson ◽

Christopher D. Anderson ◽

Joey P. Granger ◽

...

Keyword(s):

Cyclic Guanosine Monophosphate ◽

Guanosine Monophosphate ◽

Sprague Dawley ◽

Pregnant Rats ◽

No Donor ◽

Induced Hypertension ◽

Cgmp Signaling ◽

Uterine Perfusion ◽

Plasma Leptin ◽

Placental Ischemia

The prevalence of preeclampsia and obesity have increased. While obesity is a major risk factor for preeclampsia, the mechanisms linking these morbidities are poorly understood. Circulating leptin levels increase in proportion to fat mass. Infusion of this adipokine elicits hypertension in non-pregnant rats, but less is known about how hyperleptinemia impacts blood pressure during placental ischemia, an initiating event in the pathophysiology of hypertension in preeclampsia. We tested the hypothesis that hyperleptinemia during reduced uterine perfusion pressure (RUPP) exaggerates placental ischemia-induced hypertension. On gestational day (GD) 14, Sprague-Dawley rats were implanted with osmotic mini-pumps delivering recombinant rat leptin (1 mg/kg per min, i.v.) or vehicle concurrently with the RUPP procedure to induce placental ischemia or Sham. On GD 19, plasma leptin was elevated in Sham+Leptin and RUPP+Leptin. Leptin infusion did not significantly impact mean arterial pressure (MAP) in Sham. MAP was increased in RUPP+Vehicle vs. Sham+Vehicle. In contrast to our hypothesis, placental ischemia-induced hypertension was attenuated by leptin infusion. To examine potential mechanisms for attenuation of RUPP-induced hypertension during hyperleptinemia, endothelial-dependent vasorelaxation to acetylcholine was similar between Sham and RUPP; however, endothelial-independent vasorelaxation to the nitric oxide (NO)-donor, sodium nitroprusside, was increased in Sham and RUPP. These findings suggest that NO/cyclic guanosine monophosphate (cGMP) signaling was increased in the presence of hyperleptinemia. Plasma cGMP was elevated in Sham and RUPP hyperleptinemic groups compared to vehicle groups but plasma and vascular NO metabolites were reduced. These data suggest that hyperleptinemia during placental ischemia attenuates hypertension by compensatory increases in NO/cGMP signaling.

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Abstract 269: 5-aminoimidazole-4-carboxamide-3-ribonucleoside (AICAR) Decreases Soluble Fms-like Tyrosine Kinase-1 (sFlt-1) and Attenuates Endoplasmic Reticulum Stress in Rat Placental Villi Explants

Hypertension ◽

10.1161/hyp.62.suppl_1.a269 ◽

2013 ◽

Vol 62 (suppl_1) ◽

Author(s):

Christopher T Banek ◽

Haley E Gillham ◽

Sarah M Johnson ◽

Hans C Dreyer ◽

Jeffrey S Gilbert

Keyword(s):

Endoplasmic Reticulum ◽

Er Stress ◽

De Novo ◽

Vegf Receptor ◽

Sprague Dawley ◽

Hypoxic Conditions ◽

Ampk Phosphorylation ◽

Angiogenic Balance ◽

Placental Villi ◽

Placental Ischemia

Preeclampsia, defined by the onset of de novo hypertension and proteinuria near the 20th week of gestation, is a major contributor to maternal and fetal morbidity and mortality worldwide. Preeclampsia is often preceded by placental ischemia and an imbalance in circulating angiogenic factors (e.g. VEGF - vascular endothelial growth factor, sFlt-1 - soluble VEGF receptor 1). Recent studies also report increased expression of endoplasmic reticulum (ER) stress products in preeclamptic placentas. Our laboratory recently reported 5-aminoimidazole-4-carboxamide-3-ribonuceloside (AICAR) reduces blood pressure and improves angiogenic balance (increased VEGF, decreased sFlt-1) in rats with placental ischemia-induced hypertension, but the mechanism is unclear. We hypothesized AICAR would decrease sFlt-1, increase AMPK phosphorylation, and decrease ER stress in hypoxic placental villous explants. On day 19 of pregnancy, placentas were isolated from four Sprague-Dawley rats and immediately dissected in ice-cold phosphate-buffered saline. Explants were cultured for 12 hours in physiologic normoxic (8% O2) and hypoxic (1.5% O2) conditions. All experiments were performed in triplicate. VEGF secretion was unaffected by AICAR treatment in both normoxic and hypoxic conditions. AICAR decreased sFlt -1 secretion in hypoxic villi (2147±116 vs. *1411±67, P<0.05). Additionally, AMPK activation ratio was increased with AICAR, and was hypoxic-dependent (8%: 2.9±0.3; 8%+A: 3.3±0.1; 1.5%: 3.5±0.1; 1.5%+A: *4.5±0.01;*P<.05). Moreover, markers of ER stress were increased with hypoxia, and decreased with AICAR treatment (BiP 8%: 1.2±0.2; 8%+A: 1.0±0.0; 1.5%: *8.3±0.7; 1.5%+A: 1.9±0.0.3;*P<.05), (CHOP 8%: 0.5±0.0; 8%+A: 0.3±0.1; 1.5%: *1.7±0.1; 1.5%+A: 0.7±0.1;*P<.05). ATF4 was not changed with hypoxia or AICAR treatment. The present data show that AICAR stimulates AMPK phosphorylation and decreases ER stress response proteins in hypoxic placental villi. Further, the present data support the hypothesis that AICAR restores angiogenic balance by decreasing sFlt-1 rather than increasing VEGF secretion from placental villi. These findings suggest AICAR may improve placental function during pregnancies complicated by placental-ischemia.

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Placental ischemia-stimulated T-helper 17 cells induce preeclampsia-associated cytolytic natural killer cells during pregnancy

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00061.2018 ◽

2018 ◽

Vol 315 (2) ◽

pp. R336-R343 ◽

Cited By ~ 9

Author(s):

Corbin A. Shields ◽

Maggie McCalmon ◽

Tarek Ibrahim ◽

Dakota L. White ◽

Jan M. Williams ◽

...

Keyword(s):

Mean Arterial Pressure ◽

Arterial Pressure ◽

Natural Killer ◽

Cell Activation ◽

Fetal Weight ◽

T Helper ◽

T Helper 17 ◽

Placental Ischemia ◽

In Pregnancy

Previous studies have demonstrated that T-helper 17 (TH17) cells and cytolytic natural killer (cNK) cells are increased in women with preeclampsia. In this study we investigated the role of placental ischemia-stimulated TH17 cells in induction of cNK cells in pregnancy. We further assessed the role of TH17 cell-mediated oxidative stress in facilitation of cNK cell activation in pregnancy by treating rats with the SOD mimetic tempol. CD4+/CD25− cells were isolated from reduced uterine perfusion pressure (RUPP) rats and differentiated into TH17 cells in vitro. On day 12 of gestation ( GD12), 1 × 106 placental ischemia-stimulated TH17 cells were injected into normal pregnant (NP) rats (NP + RUPP TH17 rats), and a subset of rats were treated with tempol (30 mg·kg−1·day−1) from GD12 to GD19 (NP + RUPP TH17 + tempol rats). On GD19, cNK cells, mean arterial pressure, fetal weight, and cNK cell-associated cytokines and proteins were measured. Placental cNK cells were 2.9 ± 1, 14.9 ± 4, and 2.8 ± 1.0% gated in NP, NP + RUPP TH17, and NP + RUPP TH17 + tempol rats, respectively. Mean arterial pressure increased from 96 ± 5 mmHg in NP rats to 118 ± 2 mmHg in NP + RUPP TH17 rats and was 102 ± 3 mmHg in NP + RUPP TH17 + tempol rats. Fetal weight was 2.37 ± 0.04, 1.95 ± 0.14, and 2.3 ± 0.05 g in NP, NP + RUPP TH17, and NP + RUPP TH17 + tempol rats, respectively. Placental IFNγ increased from 1.1 ± 0.6 pg/mg in NP rats to 3.9 ± 0.6 pg/mg in NP + RUPP TH17 rats. Placental perforin increased from 0.18 ± 0.18 pg/mg in NP rats to 2.4 ± 0.6 pg/mg in NP + RUPP TH17 rats. Placental levels of granzymes A and B followed a similar pattern. Treatment with tempol did not lower placental cNK cytokines or proteins. The results of the present study identify TH17 cells as a mediator of aberrant NK cell activation that is associated with preeclampsia.

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Endovascular Management of Middle Aortic Syndrome Presenting with Uncontrolled Hypertension

Case Reports in Vascular Medicine ◽

10.1155/2018/9586025 ◽

2018 ◽

Vol 2018 ◽

pp. 1-4

Author(s):

Owen S. Glotzer ◽

Kathryn Bowser ◽

F. Todd Harad ◽

Sandra Weiss

Keyword(s):

Open Surgery ◽

Unusual Case ◽

Case Series ◽

Uncontrolled Hypertension ◽

Endovascular Management ◽

Vascular Disorder ◽

Middle Aortic Syndrome ◽

Surgical Bypass ◽

Endovascular Approach

Middle Aortic Syndrome is a rare vascular disorder consisting of narrowing or stenosis of the distal thoracic or abdominal aorta. It is described in the literature in the form of case studies and case series. The authors present an unusual case of Middle Aortic Syndrome attributed to Takayasu’s arteritis in a 60-year-old female who presented to the emergency department with uncontrolled hypertension. Traditional intervention involves open surgical bypass. This case study reviews the published literature on this rare syndrome and illustrates a successful alternative to open surgery through an endovascular approach.

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Behcet’s Disease: An In-depth Review About Pathogenesis, Gastrointestinal Manifestations And Management

Inflammatory Intestinal Diseases ◽

10.1159/000520696 ◽

2021 ◽

Author(s):

Anthony Nguyen ◽

Shubhra Upadhyay ◽

Muhammad Ali Javaid ◽

Abdul Moiz Qureshi ◽

Shahan Haseeb ◽

...

Keyword(s):

Behçet’S Disease ◽

Behcet’S Disease ◽

Behçet's Disease ◽

Age Groups ◽

Clinical Manifestations ◽

Signs And Symptoms ◽

Vascular Disorder ◽

Robust Algorithms ◽

Behcet's Disease ◽

Relapsing Remitting

Background: Behcet’s Disease (BD) is a complex inflammatory vascular disorder that follows a relapsing-remitting course with diverse clinical manifestations. The prevalence of the disease varies throughout the globe and targets different age groups. There are many variations of BD, however, intestinal BD is not only more common but has many signs and symptoms. Summary: BD is a relapsing-remitting inflammatory vascular disorder with multiple system involvement, affecting vessels of all types and sizes that targets young adults. The etiology of BD is unknown but many factors including genetic mechanisms, vascular changes, hypercoagulability and dysregulation of immune function are believed to be responsible. BD usually presents with signs and symptoms of ulcerative disease of the small intestine; endoscopy being consistent with the clinical manifestations. The mainstay of treatment depends upon the severity of the disease. Corticosteroids are recommended for severe forms of the disease and aminosalicylic acids are used in maintaining remission in mild to moderate forms of the disease. Key messages: In this review, we have tried to summarize in the present review the clinical manifestations, differential diagnoses and management of intestinal BD. Hopefully, this review will enable health policymakers to ponder over establishing clear endpoints for treatment, surveillance investigations and creating robust algorithms.

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Aminoimidazole carboxamide ribonucleotide administration attenuates placental‐ischemia‐induced hypertension and angiogenic imbalance in rats

The FASEB Journal ◽

10.1096/fasebj.26.1_supplement.1097.2 ◽

2012 ◽

Vol 26 (S1) ◽

Author(s):

Christopher T Banek ◽

Ashley J Bauer ◽

Mitchell B Rasmussen ◽

Hans C Dreyer ◽

Jeffrey S Gilbert

Keyword(s):

Induced Hypertension ◽

Placental Ischemia

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