Endogenous Interleukin-10 Inhibits Angiotensin II–Induced Vascular Dysfunction

Didion, Sean P.; Kinzenbaw, Dale A.; Schrader, Laura I.; Chu, Yi; Faraci, Frank M.

doi:10.1161/hypertensionaha.109.137158

Cited by 148 publications

(142 citation statements)

References 35 publications

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“…[65][66][67][68] Mice deficient in IL-10, an important product of Tregs, develop similar degrees of hypertension in response to angiotensin II, but have severe endothelial dysfunction and vessels from these mice show an increased superoxide production when incubated with angiotensin II. 69 These and other data suggest that Treg-derived IL-10 mediates the beneficial effects of Tregs in hypertension. 70 IL-2/anti-IL-2 immune complex treatment of hypertensive mice expands Tregs and reduces aortic stiffening.…”

Section: Tregs and Il-10mentioning

confidence: 88%

Immune Mechanisms in Arterial Hypertension

Wenzel¹,

Turner²,

Krebs³

et al. 2016

Journal of the American Society of Nephrology

171

148

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Traditionally, arterial hypertension and subsequent end-organ damage have been attributed to hemodynamic factors, but increasing evidence indicates that inflammation also contributes to the deleterious consequences of this disease. The immune system has evolved to prevent invasion of foreign organisms and to promote tissue healing after injury. However, this beneficial activity comes at a cost of collateral damage when the immune system overreacts to internal injury, such as prehypertension. Renal inflammation results in injury and impaired urinary sodium excretion, and vascular inflammation leads to endothelial dysfunction, increased vascular resistance, and arterial remodeling and stiffening. Notably, modulation of the immune response can reduce the severity of BP elevation and hypertensive endorgan damage in several animal models. Indeed, recent studies have improved our understanding of how the immune response affects the pathogenesis of arterial hypertension, but the remarkable advances in basic immunology made during the last few years still await translation to the field of hypertension. This review briefly summarizes recent advances in immunity and hypertension as well as hypertensive end-organ damage.

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Section: Tregs and Il-10mentioning

confidence: 88%

Immune Mechanisms in Arterial Hypertension

Wenzel¹,

Turner²,

Krebs³

et al. 2016

Journal of the American Society of Nephrology

171

148

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“…The relaxation by acetylcholine in aortic rings of C101A/ eNOS-KO was found to be mediated by NO and developed at tissue levels of superoxide and/or peroxynitrite, resembling those occurring in various animal models with clearly detectable impairment of eNOS function and/or endothelialdependent vasodilation (2,7,15,21,32,33,61). However, in each of these studies, concomitant conditions, such as atherosclerosis, severe hypertension, diabetes, or disruption of certain genes such as interleukin 10 or Bmal1, were present, which might have contributed to endothelial dysfunction beside oxidative and/or nitrosative stress.…”

Section: -5) (E)mentioning

confidence: 89%

Impact of eNOS-Dependent Oxidative Stress on Endothelial Function and Neointima Formation

Suvorava

Nagy

Pick

et al. 2015

Antioxidants & Redox Signaling

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Aims: Vascular oxidative stress generated by endothelial NO synthase (eNOS) was observed in experimental and clinical cardiovascular disease, but its relative importance for vascular pathologies is unclear. We investigated the impact of eNOS-dependent vascular oxidative stress on endothelial function and on neointimal hyperplasia. Results: A dimer-destabilized mutant of bovine eNOS where cysteine 101 was replaced by alanine was cloned and introduced into an eNOS-deficient mouse strain (eNOS-KO) in an endothelial-specific manner. Destabilization of mutant eNOS in cells and eNOS-KO was confirmed by the reduced dimer/monomer ratio. Purified mutant eNOS and transfected cells generated less citrulline and NO, respectively, while superoxide generation was enhanced. In eNOS-KO, introduction of mutant eNOS caused a 2.3-3.7-fold increase in superoxide and peroxynitrite formation in the aorta and myocardium. This was completely blunted by an NOS inhibitor. Nevertheless, expression of mutant eNOS in eNOS-KO completely restored maximal aortic endothelium-dependent relaxation to acetylcholine. Neointimal hyperplasia induced by carotid binding was much larger in eNOS-KO than in mutant eNOS-KO and C57BL/6, while the latter strains showed comparable hyperplasia. Likewise, vascular remodeling was blunted in eNOS-KO only. Innovation: Our results provide the first in vivo evidence that eNOS-dependent oxidative stress is unlikely to be an initial cause of impaired endothelium-dependent vasodilation and/or a pathologic factor promoting intimal hyperplasia. These findings highlight the importance of other sources of vascular oxidative stress in cardiovascular disease. Conclusion: eNOS-dependent oxidative stress is unlikely to induce functional vascular damage as long as concomitant generation of NO is preserved. This underlines the importance of current and new therapeutic strategies in improving endothelial NO generation. Antioxid. Redox Signal. 23, 711-723.

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“…Firstly, as the most temporal immunosuppressive and anti-inflammatory molecule, IL-10 maintains the balance of the utero-placental produced pro-inflammatory and anti-inflammatory factors [8]. Secondly, recent studies showed that IL-10 promotes de novo angiogenesis at the maternal-fetal interface through inducing production of vascular endothelial growth factor, consequently improves implantation and placental development [9,39]. In addition, IL-10 emerges as a novel modulator of the endoplasmic reticulum (ER) stress, which is essential to protein synthesis and energy balance.…”

Section: Discussionmentioning

confidence: 99%

Association of interleukin-10 gene promoter polymorphisms with recurrent pregnancy loss: a meta-analysis

Gong

Zhang

et al. 2016

J Assist Reprod Genet

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Purpose It has been reported single-nucleotide polymorphisms (SNPs) of the IL-10 promoter might be associated with the susceptibility to recurrent pregnancy loss (RPL). Owing to the inconclusive results, we conducted a meta-analysis to systematically summarize and clarify the association between the IL-10 promoter SNPs and RPL risk. Methods A systematic search of studies on the association of the three SNPs with RPL was conducted in PubMed and Embase. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were used to pool the effect size. Result Eleven case-control studies on rs1800896, seven studies on rs1800871, and eight studies on rs1800872 were included. A significant association was identified between IL-10 rs1800896 with RPL risk (G versus A: OR = 1.21, 95 % CI 1.09-1.35). No evidence of association was found between rs1800871 and RPL when restricted to those studies in Hardy-Weinberg equilibrium in controls (T versus C: OR = 1.25, 95 % CI 0.76-2.06). No statistical association was demonstrated between rs1800872 and RPL (C versus A: OR = 1.08, 95 % CI 0.83-1.42). Conclusions IL-10 rs1800896 significantly increases the risk of RPL, while rs1800872 is not correlated with RPL risk. No significant association is demonstrated between rs1800871 and RPL risk but this requires further investigation.

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Endogenous Interleukin-10 Inhibits Angiotensin II–Induced Vascular Dysfunction

Cited by 148 publications

References 35 publications

Immune Mechanisms in Arterial Hypertension

Immune Mechanisms in Arterial Hypertension

Impact of eNOS-Dependent Oxidative Stress on Endothelial Function and Neointima Formation

Association of interleukin-10 gene promoter polymorphisms with recurrent pregnancy loss: a meta-analysis

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