Hypertension, inflammation and T lymphocytes are increased in a rat model of HELLP syndrome

Wallace, Kedra; Morris, Rachael; Kyle, Patrick B.; Cornelius, Denise C.; Darby, Marie; Scott, Julie; Moseley, Janae; Chatman, Krystal; LaMarca, Babbette

doi:10.3109/10641955.2013.835820

Cited by 32 publications

(67 citation statements)

References 58 publications

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“…Similar to what was seen in placental secretion of ET-1, conditioned media from HELLP placentas did not significantly increase ET-1 production from HUVECs at either 6 hours (71. 21 …”

Section: Secretion Of Huvec Et-1 Is Increased When Exposed To Serum Fmentioning

confidence: 97%

Hypertension in an Animal Model of HELLP Syndrome is Associated With Activation of Endothelin 1

et al. 2016

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Women with hypertensive forms of pregnancy such as hemolysis-elevated liver enzymes-low platelet syndrome have increased circulating endothelin 1; however, the relationship between hypertension and endothelin 1 has not been studied. Using an animal model, we sought to determine whether there was an increased activation/dysfunction of endothelin 1, the effect of endothelin 1 receptor-A blockade on hypertension and other manifestations of hemolysis, elevated liver enzymes, and low platelets syndrome. On gestational day 12, timed-pregnant rats were infused with soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEndoglin; 4.7 and 7 µg/kg) via mini-osmotic pumps for 8 days. A subset of rats were treated with receptor-A antagonist (ABT-627, 5mg/kg) for 8 days. Rats with hemolysis-elevated liver enzymes-low platelet syndrome had significantly increased hypertension (P = .0001), circulating endothelin 1 (P = .03), and a significant 3.3- and 7.2-fold increase in preproendothelin messenger RNA (mRNA) expression in the placenta and liver (P = .01 and .04). Urinary protein:creatinine ratio was significantly increased in these animals (P = .0007), and circulating factors from these rats stimulated a significant increase in endothelial cell secretion of endothelin 1 (P = .001) in an in vitro assay. Blockade of the endothelin 1 receptor A significantly decreased hypertension (P = .001), circulating endothelin 1, and interleukin 17 (P = .004 and .003), placental preproendothelin mRNA expression (P = .016), and urinary protein:creatinine ratio (P = .007) in rats with hemolysis-elevated liver enzymes-low platelet syndrome. Blockade of the endothelin 1 receptor A significantly decreased hemolysis (P = .009), liver enzymes (P = .011), and significantly increased platelet levels (P = .03) and decreased circulating CD4+ and CD8+ T lymphocytes (P = .0004 and .0001) in rats infused with sFlt-1 and sEndoglin. These data support the hypothesis that endothelin 1 activation has a critical role in pathophysiology of as hemolysis-elevated liver enzymes-low platelet syndrome.

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“…Similar to what was seen in placental secretion of ET-1, conditioned media from HELLP placentas did not significantly increase ET-1 production from HUVECs at either 6 hours (71. 21 …”

Section: Secretion Of Huvec Et-1 Is Increased When Exposed To Serum Fmentioning

confidence: 97%

Hypertension in an Animal Model of HELLP Syndrome is Associated With Activation of Endothelin 1

et al. 2016

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“…However, CD8 + T cells are associated with neuroinflammatory conditions such as neurological paraneoplastic syndromes and multiple sclerosis 15, 16 . As CD4 + and CD8 + T cells are increased in response to infusion of sFlt-1 and sEng 9, 10 we sought to determine if 1) rats with HELLP syndrome had an increase in BBB permeability and 2) if T cells contributed to the inflammation and any potential increase in BBB permeability in an animal model of HELLP syndrome.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of T‐cell activation attenuates hypertension,TNFα,IL‐17, and blood–brain barrier permeability in pregnant rats with angiogenic imbalance

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Spencer

Bowles

et al. 2016

American J Rep Immunol

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Problem Angiogenic imbalance during pregnancy is associated with immune activation, hypertension, increased T cell infiltration, and neurological insults. Method of Study On gestational day (GD) 12 timed-pregnant rats were infused with anti-angiogenic factors sFlt-1 and sEndoglin (4.7 and 7μg/kg) to create HELLP syndrome via mini-osmotic pumps for 8 days, with a subset of these rats having Orencia (2mg/kg) infused on GD13. On GD19, blood brain barrier (BBB) permeability was evaluated via Evan’s Blue infusion, blood was collected for T cell measurements, inflammatory cytokine secretion. Brain tissues were also collected to examine inflammatory cytokine infiltration. Results T cell attenuation with Orencia decreased circulating CD4+ and CD8+ T cells, circulating TNFα and IL-17, BBB permeability and significantly decreased biochemical evidence of HELLP compared to untreated HELLP rats. Conclusions These data support the hypothesis that T cells have a critical role in contributing to the pathophysiology that is seen in angiogenic imbalance during pregnancy.

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“…T lymphocytes are also thought to play a critical role in the pathogenesis of hypertension and vascular remodelling [9]. Recent data from experimental animal models found that T cells are associated with hypertension and inflammation [10]. It has been shown that potassium channels are essential for the activation of T lymphocytes, and that they are involved in multiple physiological processes, such as T lymphocyte differentiation, proliferation, and activation [11,12].…”

Section: Introductionmentioning

confidence: 99%

Potassium channel changes of peripheral blood T-lymphocytes from Kazakh hypertensive patients in Northwest China and the inhibition effect towards potassium channels by telmisartan

et al. 2016

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A b s t r a c tBackground and aim: Increasing evidence indicates that chronic inflammation is a direct or indirect manifestation of hypertension. Potassium channels are thought to be critical for lymphocyte activation, which suggests that hypertension may be an inflammatory disease initiated at the ion channel level. Methods:This study investigated changes in interleukin (IL)-6, IL-17, and transforming growth factor beta (TGF-b1) expression in the blood of Kazakh hypertensive patients in Northwest China using ELISA technology. Whole-cell patch clamp technology was used to evaluate current changes associated with Kv1.3 and KCa3.1 in peripheral blood T lymphocytes of hypertensive patients, and to investigate current changes induced by telmisartan. We also investigated the effects of telmisartan on expression of Kv1.3 and KCa3.1 at mRNA and protein levels in peripheral blood T lymphocytes using real-time polymerase chain reaction and Western blot analysis. Results:Expression of IL-6, IL-17 and TGF-b1 in the blood of Kazakh hypertensive patients in Northwest China was significantly higher than in healthy controls (p < 0.05). The current mediated by Kv1.3 and KCa3.1 and the corresponding expression at mRNA and protein levels in T lymphocytes were also higher in these hypertensive patients than in controls (p < 0.05). Telmisartan intervention for 24 h and 48 h inhibited the current and expression of Kv1.3 and KCa3.1 at mRNA and protein levels (p < 0.05). Conclusions:These results indicated that the increase in functional Kv1.3 and KCa3.1 channels expressed in T lymphocytes of Kazakh patients with hypertension was blocked by telmisartan, resulting in a reduced inflammatory response. These results provide theoretical support for the treatment of hypertension at the cellular ion channel level.

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Hypertension, inflammation and T lymphocytes are increased in a rat model of HELLP syndrome

Cited by 32 publications

References 58 publications

Hypertension in an Animal Model of HELLP Syndrome is Associated With Activation of Endothelin 1

Hypertension in an Animal Model of HELLP Syndrome is Associated With Activation of Endothelin 1

Inhibition of T‐cell activation attenuates hypertension,TNFα,IL‐17, and blood–brain barrier permeability in pregnant rats with angiogenic imbalance

Potassium channel changes of peripheral blood T-lymphocytes from Kazakh hypertensive patients in Northwest China and the inhibition effect towards potassium channels by telmisartan

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