TNF-α impairs endothelial function in adipose tissue resistance arteries of mice with diet-induced obesity

Donato, Anthony J.; Henson, Grant D.; Morgan, R. Garrett; Enz, Ryley A.; Walker, Ashley E.; Lesniewski, Lisa A.

doi:10.1152/ajpheart.00271.2012

Cited by 49 publications

(53 citation statements)

References 45 publications

(64 reference statements)

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“…For example, adipose tissue plays an integral role in endothelial inflammation through the release of TNF-α and subsequent expression of inflammatory cytokines and adhesion molecules exacerbating obesity-related vascular disease (44). Consistent with our hypothesis, metformin exhibited the effects of the AMPK-PARP-1-Bcl-6 anti-inflammatory cascade in adipocytes to mitigate TNF-α-induced inflammation (Fig.…”

Section: Discussionsupporting

confidence: 83%

AMPKα2 exerts its anti-inflammatory effects through PARP-1 and Bcl-6

Gongol

Marin

Peng

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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B-cell lymphoma-6 protein (Bcl-6) is a corepressor for inflammatory mediators such as vascular cell adhesion molecule-1 and monocyte chemotactic protein-1 and -3, which function to recruit monocytes to vascular endothelial cells upon inflammation. Poly [ADP ribose] polymerase 1 (PARP-1) is proinflammatory, in part through its binding at the Bcl-6 intron 1 to suppress Bcl-6 expression. We investigated the mechanisms by which PARP-1 dissociates from the Bcl-6 intron 1, ultimately leading to attenuation of endothelial inflammation. Analysis of the PARP-1 primary sequence suggested that phosphorylation of PARP-1 Serine 177 (Ser-177) by AMP-activated protein kinase (AMPK) is responsible for the induction of Bcl-6. Our results show that AMPK activation with treatment of 5-aminoimidazole-4-carboxamide ribonucleotide, metformin, or pulsatile shear stress induces PARP-1 dissociation from the Bcl-6 intron 1, increases Bcl-6 expression, and inhibits expression of inflammatory mediators. Conversely, AMPKα suppression or knockdown produces the opposite effects. The results demonstrate an anti-infamatory pathway linking AMPK, PARP-1, and Bcl-6 in endothelial cells.

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Section: Discussionsupporting

confidence: 83%

AMPKα2 exerts its anti-inflammatory effects through PARP-1 and Bcl-6

Gongol

Marin

Peng

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…However, this might indicate that more TNF-␣ is bound to its receptor thereby exerting more biological activity and vascular dysfunction in obese preeclamptic women or that, in obesity, less TNF-␣ is needed to promote vascular dysfunction. In support of this theory, although only performed in male mice, it was demonstrated that HFD-induced obesity is associated with greater TNF-␣-induced impairment of endothelium/NOmediated vasorelaxation in resistance arteries isolated from white adipose tissue even though plasma levels of this cytokine were similar between normal diet and HFD groups (41). It should be considered that this phenomenon may result from local production of TNF-␣ in adipose or the vasculature per se that can impact arterial function without reaching the circulation.…”

Section: Effects Of Obesity On Placental Ischemia-induced Endothelialmentioning

confidence: 94%

Increased risk for the development of preeclampsia in obese pregnancies: weighing in on the mechanisms

Spradley

Palei

Granger

2015

American Journal of Physiology-Regulatory, Integrative and Comp

113

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) is a pregnancy-specific disorder typically presenting as new-onset hypertension and proteinuria. While numerous epidemiological studies have demonstrated that obesity increases the risk of PE, the mechanisms have yet to be fully elucidated. Growing evidence from animal and human studies implicate placental ischemia in the etiology of this maternal syndrome. It is thought that placental ischemia is brought about by dysfunctional cytotrophoblast migration and invasion into the uterus and subsequent lack of spiral arteriole widening and placental perfusion. Placental ischemia/ hypoxia stimulates the release of soluble placental factors into the maternal circulation where they cause endothelial dysfunction, particularly in the kidney, to elicit the clinical manifestations of PE. The most recognized of these factors are the anti-angiogenic sFlt-1 and pro-inflammatory TNF-␣ and AT1-AA, which promote endothelial dysfunction by reducing levels of the provasodilator nitric oxide and stimulating production of the potent vasoconstrictor endothelin-1 and reactive oxygen species. We hypothesize that obesity-related metabolic factors increase the risk for developing PE by impacting various stages in the pathogenesis of PE, namely, 1) cytotrophoblast migration and placental ischemia; 2) release of soluble placental factors into the maternal circulation; and 3) maternal endothelial and vascular dysfunction. This review will summarize the current experimental evidence supporting the concept that obesity and metabolic factors like lipids, insulin, glucose, and leptin affect placental function and increase the risk for developing hypertension in pregnancy by reducing placental perfusion; enhancing placental release of soluble factors; and by increasing the sensitivity of the maternal vasculature to placental ischemia-induced soluble factors. body mass index; inflammation; placental ischemia; pregnancy; RUPP; sFlt-1 PE IS A PREGNANCY-SPECIFIC DISORDER typically identified by new-onset hypertension in the second half of pregnancy. Although often accompanied by new-onset proteinuria, PE can be associated with many other signs and symptoms including headaches, visual disturbances, epigastric pain, and the development of edema (4,192). Globally, this disease affects over 8 million pregnancies per year and is estimated to account for 40 -60% of maternal deaths in developing countries (125). In the United States, there was a 25% increase in the rate of PE between the years 1987-2004 (189). This significant increase highlights the importance of understanding how risk factors like obesity play a role in the pathogenesis of this maternal syndrome. Obesity is defined as a body mass index (BMI) of greater than or equal to 30 kg/m 2 . Greater than one-half of pregnant women are overweight or obese (48), and more than two-thirds of reproductive-aged women in the United States are overweight or obese (49). Although mounting epidemiological evidence supports obesity as a major risk factor for PE, the mechanisms linking these two morbidities are...

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“…Previous studies have demonstrated an impairment of relaxant responses in the aorta, mesenteric 9 , femoral, and coronary arteries 10 in experimental models of obesity, that were associated with diminished NO release. The impaired vascular function and an increased vascular oxidative stress observed in obesity were associated with increased levels of inflammatory adipocytokines such as leptin, and tumor necrosis factor alpha -TNF-α, as well as decreased levels of anti-inflammatory adipocytokines such as adiponectin 11 .…”

Section: Vascular Dysfunction In Obesitymentioning

confidence: 99%

Vascular dysfunction in obesity: Beneficial effects of aerobic exercise training in animal models

Sponton

Sousa

Delbin

2017

Motriz: rev. educ. fis.

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-Cardiovascular disease (CVD) is the leading cause of mortality in the world and several risk factors for developing CVD have been pointed out, including obesity and physical inactivity. Endothelial dysfunction as a consequence of metabolic and inflammatory disorders plays an important role in the onset of vascular complications in obesity. In addition, it is well established that aerobic exercises promote beneficial effects on CVD by increasing nitric oxide (NO) production or its bioavailability in human and experimental models. The interest in exercise studies increased significantly, with promising results. Considering the importance of this field, the purpose of this mini-review is to summarize the animal studies that investigated the physiological mechanisms of vascular dysfunction in obesity and how aerobic exercise training influenced these alterations.

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TNF-α impairs endothelial function in adipose tissue resistance arteries of mice with diet-induced obesity

Cited by 49 publications

References 45 publications

AMPKα2 exerts its anti-inflammatory effects through PARP-1 and Bcl-6

AMPKα2 exerts its anti-inflammatory effects through PARP-1 and Bcl-6

Increased risk for the development of preeclampsia in obese pregnancies: weighing in on the mechanisms

Vascular dysfunction in obesity: Beneficial effects of aerobic exercise training in animal models

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