Vascular Dysfunction in Ocular Blood Flow Regulation: Impact of Reactive Oxygen Species in an Experimental Setup

Wagenfeld, Lars; Weiss, Sonja; Klemm, M.; Richard, Gisbert; Zeitz, Oliver

doi:10.1167/iovs.14-14032

Cited by 7 publications

(4 citation statements)

References 31 publications

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“…Reduction of blood flow in various organs induces cellular damage by producing reactive oxygen species (ROS) and releasing inflammatory cytokines [75,76,77,78]. In our study, mice with PTS exhibited significantly higher levels of antioxidant enzymatic scavengers such as catalase and HO-1 as compared to mice with TTS (Figure 8a,b), which indicates that PTS induces the production of excessive free radical species that require increased ROS detoxification.…”

Section: Discussionmentioning

confidence: 58%

Acoustic Trauma Modulates Cochlear Blood Flow and Vasoactive Factors in a Rodent Model of Noise-Induced Hearing Loss

Shin

Lyu

Jeong

et al. 2019

IJMS

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Noise exposure affects the organ of Corti and the lateral wall of the cochlea, including the stria vascularis and spiral ligament. Although the inner ear vasculature and spiral ligament fibrocytes in the lateral wall consist of a significant proportion of cells in the cochlea, relatively little is known regarding their functional significance. In this study, 6-week-old male C57BL/6 mice were exposed to noise trauma to induce transient hearing threshold shift (TTS) or permanent hearing threshold shift (PTS). Compared to mice with TTS, mice with PTS exhibited lower cochlear blood flow and lower vessel diameter in the stria vascularis, accompanied by reduced expression levels of genes involved in vasodilation and increased expression levels of genes related to vasoconstriction. Ultrastructural analyses by transmission electron microscopy revealed that the stria vascularis and spiral ligament fibrocytes were more damaged by PTS than by TTS. Moreover, mice with PTS expressed significantly higher levels of proinflammatory cytokines in the cochlea (e.g., IL-1β, IL-6, and TNF-α). Overall, our findings suggest that cochlear microcirculation and lateral wall pathologies are differentially modulated by the severity of acoustic trauma and are associated with changes in vasoactive factors and inflammatory responses in the cochlea.

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Section: Discussionmentioning

confidence: 58%

Acoustic Trauma Modulates Cochlear Blood Flow and Vasoactive Factors in a Rodent Model of Noise-Induced Hearing Loss

Shin

Lyu

Jeong

et al. 2019

IJMS

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“…Endothelium-derived oxygen species, which are abundant in preeclampsia, 29 induce further vasoconstriction in precontracted ophthalmic arteries and thus may contribute to further progression of diseases involving altered blood flow and vascular tone, such as hypertension. 30 These opposing mechanisms in the perivascular retinal tissue may lead to arteriolar stiffening and decreased AA, which is possibly compensated for by increased MAP. 15 In preeclampsia, we did not find significant differences in baseline vessel diameters compared with NP and NC, with adjustment for confounders, including MAP.…”

Section: Discussionmentioning

confidence: 99%

Altered Retinal Flicker Response Indicates Microvascular Dysfunction in Women With Preeclampsia

Brückmann¹,

Seeliger²,

Lehmann³

et al. 2015

Hypertension

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Abstract-Flicker-induced dilatation is reduced in patients with cardiovascular risk, and the following arteriolar constriction is reduced with aging, leading to a reduced arteriolar amplitude and, thereby, indicating microvascular endothelial dysfunction. As endothelial dysfunction is associated with preeclampsia, we assessed retinal flicker response during pregnancy and postpartum. Between 2006 and 2013, women were recruited from University Hospital Jena and Prenatal Diagnostic Center Erfurt, Germany, of which 34 women with preeclampsia, 45 women with normal pregnancy, and 22 nonpregnant controls were included in the study. Women with normal pregnancy were matched for age, nulliparity, smoking, previous gestational hypertensive disorders, and family history of cardiovascular disease. Nonpregnant women were age-matched, nulliparous, nonsmoking, without family history of cardiovascular disease. Retinal vessel measurement using Dynamic Vessel Analyzer consisted of 50-seconds baseline acquisition, followed by three 20-second flicker and 80-second relaxation periods. Arteriolar constriction and arteriolar amplitude were reduced during pregnancy (P=0.001 and P=0.008) and postpartum (P=0.018 and P=0.034) in women with preeclampsia, adjusted for age, body mass index, mean arterial pressure, baseline diameter, and family history of cardiovascular disease. Flicker-induced dilatation was unchanged within the groups and throughout the study period. The unchanged flicker-induced dilatation may support a preserved autoregulatory competence of the microvasculature, and the diminished arteriolar amplitude, mainly because of the absence of the arteriolar constriction, indicates a commenced retinal microvascular dysfunction in women with preeclampsia during pregnancy and postpartum. Mechanisms responsible for altered retinal flicker response in preeclampsia need to be clarified in further studies.

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“…Heart failure is associated with cardiac hypertrophy and remodeling, and the pathogenesis of CHF is, in part, attributed to cardiac oxidative stress (15,42). Increased reactive oxygen species (ROS) affects multiple biological funcitons ranging from myocyte function to excitation-contraction coupling to the regulation of coronary blood flow (1,4,49). An imbalance between the synthesis of free radicals and their elimination by antioxidant defense systems results in macromolecular damage and disruption of normal cellular redox signaling, thus affecting cardiac structure and function, contributing to the contractile dysfunction, myocardial hypertrophy, and fibrosis observed in CHF (7,40,41).…”

Section: Introductionmentioning

confidence: 99%

Myocardial infarction-induced microRNA-enriched exosomes contribute to cardiac Nrf2 dysregulation in chronic heart failure

Tian

Gao

Zimmerman

et al. 2018

American Journal of Physiology-Heart and Circulatory Physiology

131

115

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The imbalance between the synthesis of reactive oxygen species and their elimination by antioxidant defense systems results in macromolecular damage and disruption of cellular redox signaling, affecting cardiac structure and function, thus contributing to contractile dysfunction, myocardial hypertrophy, and fibrosis in chronic heart failure [chronic heart failure (CHF)]. The Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is an important antioxidant defense mechanism and is closely associated with oxidative stress-mediated cardiac remodeling in CHF. In the present study, we investigated the regulation of myocardial Nrf2 in the postmyocardial infarction (post-MI) state. Six weeks post-MI, Nrf2 protein was downregulated in the heart, resulting in a decrease of Nrf2-targeted antioxidant enzymes, whereas paradoxically the transcription of Nrf2 was increased, suggesting that translational inhibition of Nrf2 may contribute to the dysregulation in CHF. We therefore hypothesized that microRNAs may be involved in the translational repression of Nrf2 mRNA in the setting of CHF. Using quantitative real-time PCR analysis, we found that three microRNAs, including microRNA-27a, microRNA-28-3p, and microRNA-34a, were highly expressed in the left ventricle of infarcted hearts compared with other organs. Furthermore, in vitro analysis revealed that cultured cardiac myocytes and fibroblasts expressed these three microRNAs in response to TNF-α stimulation. These microRNAs were preferentially incorporated into exosomes and secreted into the extracellular space in which microRNA-enriched exosomes mediated intercellular communication and Nrf2 dysregulation. Taken together, these results suggest that increased local microRNAs induced by MI may contribute to oxidative stress by the inhibition of Nrf2 translation in CHF. NEW & NOTEWORTHY The results of this work provide a novel mechanism mediated by microRNA-enriched exosomes, contributing to the nuclear factor erythroid 2-related factor 2 dysregulation and subsequent oxidative stress. Importantly, these new findings will provide a promising strategy to improve the therapeutic efficacy through targeting nuclear factor erythroid 2-related factor 2-related microRNAs in the chronic heart failure state, which show potentially clinical applications.

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Vascular Dysfunction in Ocular Blood Flow Regulation: Impact of Reactive Oxygen Species in an Experimental Setup

Cited by 7 publications

References 31 publications

Acoustic Trauma Modulates Cochlear Blood Flow and Vasoactive Factors in a Rodent Model of Noise-Induced Hearing Loss

Acoustic Trauma Modulates Cochlear Blood Flow and Vasoactive Factors in a Rodent Model of Noise-Induced Hearing Loss

Altered Retinal Flicker Response Indicates Microvascular Dysfunction in Women With Preeclampsia

Myocardial infarction-induced microRNA-enriched exosomes contribute to cardiac Nrf2 dysregulation in chronic heart failure

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