Rho Kinase as a Target for Cerebral Vascular Disorders

Bond, Lisa M.; Sellers, James R.; McKerracher, Lisa

doi:10.4155/fmc.15.45

Cited by 19 publications

(17 citation statements)

References 160 publications

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“…ROCKs regulate contractility of endothelial cells and SMCs through dephosphorylation of myosin light chain subunits which results in cell relaxation, whereas calcium influx and activation of myosin light chain kinase counter ROCKs by promoting cell contraction (Bond et al . ; Huveneers et al . ).…”

Section: Role Of Rocks: Vascular Pathologies and Vascular Risk Factormentioning

confidence: 97%

Rho‐associated protein kinases as therapeutic targets for both vascular and parenchymal pathologies in Alzheimer's disease

Lai

McLaurin

2017

Journal of Neurochemistry

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The causes of late-onset Alzheimer's disease are unclear and likely multifactorial. Rho-associated protein kinases (ROCKs) are ubiquitously expressed signaling messengers that mediate a wide array of cellular processes. Interestingly, they play an important role in several vascular and brain pathologies implicated in Alzheimer's etiology, including hypertension, hypercholesterolemia, blood-brain barrier disruption, oxidative stress, deposition of vascular and parenchymal amyloid-beta peptides, tau hyperphosphorylation, and cognitive decline. The current review summarizes the functions of ROCKs with respect to the various risk factors and pathologies on both sides of the bloodbrain barrier and present support for targeting ROCK signaling as a multifactorial and multi-effect approach for the prevention and amelioration of late-onset Alzheimer's disease.

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Section: Role Of Rocks: Vascular Pathologies and Vascular Risk Factormentioning

confidence: 97%

Rho‐associated protein kinases as therapeutic targets for both vascular and parenchymal pathologies in Alzheimer's disease

Lai

McLaurin

2017

Journal of Neurochemistry

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“…In blood vessels, the Rho/Rho-associated protein kinase (ROCK) pathway is expressed abundantly in the vascular smooth muscle and is known to regulate vasoreactivity4445. Noteworthy in this context is that this family of proteins is recognized as key signalling molecules that regulate arterial blood pressure and are important mediators involved in maintaining vascular tone in pathophysiological conditions, such as hypertension4647. Hence, any alterations in the hemodynamic balance and level of activation of the Rho protein family members may compromise the vascular integrity and lead to various vasculopathies4348.…”

Section: Discussionmentioning

confidence: 99%

First insight into the proteome landscape of the porcine short posterior ciliary arteries: Key signalling pathways maintaining physiologic functions

Manicam

Perumal

Pfeiffer

et al. 2016

Sci Rep

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Short posterior ciliary arteries (sPCA) provide the major blood supply to the optic nerve head. Emerging evidence has linked structural and functional anomalies of sPCA to the pathogenesis of several ocular disorders that cause varying degrees of visual loss, particularly anterior ischaemic optic neuropathy and glaucoma. Although the functional relevance of this vascular bed is well-recognized, the proteome of sPCA remains uncharacterized. Since the porcine ocular system closely resembles that of the human’s and is increasingly employed in translational ophthalmic research, this study characterized the proteome of porcine sPCA employing the mass spectrometry-based proteomics strategy. A total of 1742 proteins and 10527 peptides were identified in the porcine sPCA. The major biological processes involved in the maintenance of physiological functions of the sPCA included redox and metabolic processes, and cytoskeleton organization. These proteins were further clustered into diverse signalling pathways that regulate vasoactivity of sPCA, namely the tight junction, α- and β-adrenoceptor, 14-3-3, nitric oxide synthase and endothelin-1 -mediated signalling pathways. This study provides the first insight into the complex mechanisms dictating the vast protein repertoire in normal vascular physiology of the porcine sPCA. It is envisioned that our findings will serve as important benchmarks for future studies of sPCA.

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“…Over the past decade, there has been increasing experimental evidence underlining the involvement of two isoforms of ROCK, ROCK1 and ROCK2 in numerous cardiovascular and renal disorders. The activity of this pathway is increased in disorders such as heart failure, coronary artery disease and cerebrovascular disease, all of which associated with tissue hypoxia and reduced integrity of tissue vasculature (18,19,23).…”

Section: Discussionmentioning

confidence: 99%

“…brain, heart etc.) (18,19). In a single study, ROCK activity has been shown to be increased in OSAS in correlation with increased C-reactive protein (CRP) concentration and reduced flow-mediated dilatation in the brachial artery suggesting the presence of an interplay with ROCK and endothelial dysfunction (20).…”

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confidence: 99%

Reduced Peripheral Blood Mononuclear Cell ROCK1 and ROCK2 Levels in Obstructive Sleep Apnea Syndrome

2018

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Abstract. Background Obstructive sleep apnea syndrome (OSAS) is one of the most frequent sleep disorders with a prevalence of 2-4% in the adult population, 3.1%-7.5% in men and 1.8%-5% in women (1-9). OSAS is characterized by repetitive episodes of apnea due to total compression of respiratory tract, intermittent hypoxia, reduced blood oxygen saturation and impaired sleep quality. It may cause difficulty sleeping, morning headache, daytime sleepiness, fatigue and reduced performance in daytime activities. Age, male gender and obesity have been listed among the risk factors of OSAS (1-3, 10). Moreover, OSAS has been associated with increased risk for arterial and pulmonary hypertension, cardiovascular and cerebrovascular disorders and metabolic syndrome (2,(11)(12)(13)(14).Although pathophysiological processes underlying OSAS have not been fully understood, inflammation, vascular endothelial dysfunction and altered body metabolism have been implicated (15,16). Rho-associated protein kinase (ROCK) enzyme is known to be involved in regulation of vascular functions and cardiovascular disease pathogenesis. ROCK activation has been shown to enhance endothelial permeability and induce angiogenic processes through regulation of endothelial gene expression (17). In several studies, ROCK enzyme activity has been shown to be altered in patients characterized with cardiorespiratory problems that might potentially lead to chronic hypoxia of the target tissue (e.g. brain, heart etc.) (18,19). In a single study, ROCK activity has been shown to be increased in OSAS in correlation with increased C-reactive protein (CRP) concentration and reduced flow-mediated dilatation in the brachial artery suggesting the presence of an interplay with ROCK and endothelial dysfunction (20).The present study was conducted to find out whether intermittent hypoxia induced by OSAS might alter ROCK1 and ROCK2 expression in the peripheral blood and thus levels of these proteins can be used to extrapolate the intensity of hypoxia induced by OSAS. Clinical and laboratory features that might potentially be associated with ROCK expression levels were also investigated. 319This article is freely accessible online.Correspondence to: Erdem Tüzün,

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Rho Kinase as a Target for Cerebral Vascular Disorders

Cited by 19 publications

References 160 publications

Rho‐associated protein kinases as therapeutic targets for both vascular and parenchymal pathologies in Alzheimer's disease

Rho‐associated protein kinases as therapeutic targets for both vascular and parenchymal pathologies in Alzheimer's disease

First insight into the proteome landscape of the porcine short posterior ciliary arteries: Key signalling pathways maintaining physiologic functions

Reduced Peripheral Blood Mononuclear Cell ROCK1 and ROCK2 Levels in Obstructive Sleep Apnea Syndrome

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