Endoplasmic reticulum stress inhibition reduces hypertension through the preservation of resistance blood vessel structure and function

Carlisle, Rachel E.; Werner, Kaitlyn E.; Yum, Victoria; Lü, Chao; Tat, Victor; Memon, Muzammil; No, Yejin; Ask, Kjetil; Dickhout, Jeffrey G.

doi:10.1097/hjh.0000000000000943

Cited by 38 publications

(31 citation statements)

References 51 publications

(65 reference statements)

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“…Whereas the ROS-generating role of non-NADPH oxidases in cardiovascular cells seems to be minor in physiologic conditions, 9 growing evidence suggests that ROS generated in mitochondria and the endoplasmic reticulum (ER) may contribute to oxidative stress in hypertension. [10][11][12] This likely involves cross-talk between Noxs and mitochondria/ER. In particular, the concept of ROS-induced ROS release (RIRR) may be important, whereby ROS formed in one region activate ROS in another region 13 (Fig.…”

Section: R Esum Ementioning

confidence: 99%

“…18 Treatment of SHRs with 4-PBA reduced blood pressure and improved vascular function and structure by ameliorating ER stress. 12 Although ERand mitochondria-derived ROS may contribute in part to oxidative stress in hypertension, the upstream driving factor appears to be Nox activation. 13,14 Oxidative stress and altered redox signalling are emerging as major pathogenic factors in cardiovascular disease.…”

Section: R Esum Ementioning

confidence: 99%

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Oxidative Stress: A Unifying Paradigm in Hypertension

Touyz

Ríos

Alves-Lopes

et al. 2020

Canadian Journal of Cardiology

158

129

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The etiology of hypertension involves complex interactions among genetic, environmental, and pathophysiologic factors that influence many regulatory systems. Hypertension is characteristically associated with vascular dysfunction, cardiovascular remodelling, renal dysfunction, and stimulation of the sympathetic nervous system. Emerging evidence indicates that the immune system is also important and that activated immune cells migrate and accumulate in tissues promoting inflammation, fibrosis, and target-organ damage. Common to these processes is oxidative stress, defined as an imbalance between

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Section: R Esum Ementioning

confidence: 99%

Section: R Esum Ementioning

confidence: 99%

Oxidative Stress: A Unifying Paradigm in Hypertension

Touyz

Ríos

Alves-Lopes

et al. 2020

Canadian Journal of Cardiology

158

129

View full text Add to dashboard Cite

show abstract

“…; Carlisle et al . ; Padilla & Jenkins, ); a response that is prevented when NADPH oxidase‐derived ROS production is inhibited (Kassan et al . ).…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic reticulum stress in the pathogenesis of hypertension

Young

2017

Experimental Physiology

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What is the topic of this review? This review highlights the emerging role of disruptions in endoplasmic reticulum (ER) function, namely ER stress, as a contributor to hypertension. What advances does it highlight? This review presents an integrative view of ER stress in cardiovascular control systems, including systems within the brain, kidney and peripheral vasculature, as related to development of hypertension. The endoplasmic reticulum (ER) is a cellular organelle specialized in the synthesis, folding, assembly and modification of proteins. In situations of increased protein demand, complex signalling pathways, termed the unfolded protein response, influence a series of cellular feedback loops to control ER function strictly. Although this is initially a compensatory attempt to maintain cellular homeostasis, chronic activation of the unfolded protein response, known as ER stress, leads to sustained changes in cellular function. A growing body of literature points to ER stress in diverse cardioregulatory systems, including the brain, kidney and vasculature, as central to the development of hypertension. Here, these recent findings from essential and obesity-related forms of hypertension are highlighted in an integrative manner, with discussion of the potential upstream causes and downstream consequences of ER stress. Given that hypertension is a leading medical and socio-economic global challenge, emerging findings suggest that targeting ER stress might represent a viable strategy for the treatment of hypertensive disease.

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“…Furthermore, isolated rat hearts that were pretreated with 4-PBA and subject to ischemia-reperfusion injury exhibited reduced ROS and decreased expression of markers of ER stress and cell death (52). In a model of human essential hypertension, spontaneously hypertensive rats treated with 4-PBA for 5 wk exhibited significantly lower blood pressures as well as reduced expression of 3-nitrotyrosine, a marker of ROS production (53). Although oxidative stress can induce HSF1 transcriptional activity (54-56), 4-PBA increased HSF1 nuclear localization ( Figs.…”

Section: Discussionmentioning

confidence: 99%

4‐Phenylbutyrate protects against atherosclerotic lesion growth by increasing the expression of HSP25 in macrophages and in the circulation of Apoe ^−/− mice

et al. 2019

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Endoplasmic reticulum stress plays an important role in cardiovascular disease (CVD) and atherosclerosis. We aimed to assess the ability of 4‐phenylbutyrate (4‐PBA), a small chemical chaperone administered via drinking water, to reduce atherosclerotic lesion size in chow‐fed apolipoprotein (Apo) e−/− mice and to identify mechanisms that contribute to its antiatherogenic effect. Chow‐fed 17‐wk‐old female Apoe−/− mice treated with 4‐PBA–supplemented drinking water for 5 wk exhibited smaller lesions as well as increased plasma levels of heat shock protein (HSP) 25, the mouse homolog of human HSP27, compared with controls. In addition, 4‐PBA inhibited cell death and increased HSP27 expression as measured by real‐time PCR and immunoblotting, as well as induced nuclear localization of its transcription factor, heat shock factor 1, in human monocyte/macrophage (THP‐1) cells. Furthermore, HSP27 small interfering RNA diminished the protective effect of 4‐PBA on THP‐1 macrophage attachment and differentiation. In summary, drinking water containing 4‐PBA attenuated early lesion growth in Apoe−/− mice fed a chow diet and increased expression of HSP25 and HSP27 in macrophages and HSP25 in the circulation of Apoe−/− mice. Given that increased expression of HSP27 is inversely correlated with CVD risk, our findings suggest that 4‐PBA protects against the early stages of atherogenesis in part by enhancing HSP27 levels, leading to inhibition of both macrophage cell death and monocyte‐macrophage differentiation.—Lynn, E. G., Lhoták, Š., Lebeau, P., Byun, J. H., Chen, J., Platko, K., Shi, C., O'Brien, E. R., Austin, R. C. 4‐Phenylbutyrate protects against atherosclerotic lesion growth by increasing the expression of HSP25 in macrophages and in the circulation of Apoe−/− mice. FASEB J. 33, 8406–8422 (2019). http://www.fasebj.org

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Endoplasmic reticulum stress inhibition reduces hypertension through the preservation of resistance blood vessel structure and function

Abstract: Endoplasmic reticulum stress caused endothelial-mediated vascular dysfunction contributing to elevated BP in the SHR model of human essential hypertension.

Cited by 38 publications

References 51 publications

Oxidative Stress: A Unifying Paradigm in Hypertension

Oxidative Stress: A Unifying Paradigm in Hypertension

Endoplasmic reticulum stress in the pathogenesis of hypertension

4‐Phenylbutyrate protects against atherosclerotic lesion growth by increasing the expression of HSP25 in macrophages and in the circulation of Apoe ^−/− mice

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Endoplasmic reticulum stress inhibition reduces hypertension through the preservation of resistance blood vessel structure and function

Abstract: Endoplasmic reticulum stress caused endothelial-mediated vascular dysfunction contributing to elevated BP in the SHR model of human essential hypertension.

Cited by 38 publications

References 51 publications

Oxidative Stress: A Unifying Paradigm in Hypertension

Oxidative Stress: A Unifying Paradigm in Hypertension

Endoplasmic reticulum stress in the pathogenesis of hypertension

4‐Phenylbutyrate protects against atherosclerotic lesion growth by increasing the expression of HSP25 in macrophages and in the circulation of Apoe −/− mice

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4‐Phenylbutyrate protects against atherosclerotic lesion growth by increasing the expression of HSP25 in macrophages and in the circulation of Apoe ^−/− mice