The renin-angiotensin-aldosterone system in cerebral small vessel disease

Brenner, David A.; Labreuche, Julien; Pico, Fernando; Scheltens, Philip; Poirier, O.; Cambien, François; Amarenco, Pierre

doi:10.1007/s00415-008-0816-8

Cited by 29 publications

(35 citation statements)

References 38 publications

(46 reference statements)

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“…Increasing evidence has revealed the important role of local RAAS in CNS disorders. 8,9 Inhibitors of RAAS, which are widely used as antihypertensive drugs, may have potential beneficial and therapeutic effects on CNS disorders. We and others have shown that treatment with AT 1 receptor blockers can reduce the ischemic area in the brain and improve cognitive function in various animal models.…”

Section: Discussionmentioning

confidence: 99%

“…7 However, accumulating evidence shows that RAAS that is localized in the CNS also has an important role in CNS disorders. 8,9 Recently, increased attention has focused on understanding the involvement of RAAS in the pathogenesis of neurodegenerative diseases. Kawajiri et al 10 observed a reduced Ang II level in the cerebrospinal fluid of patients with ALS.…”

Section: Introductionmentioning

confidence: 99%

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Angiotensin II and aldosterone-induced neuronal damage in neurons through an astrocyte-dependent mechanism

et al. 2011

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The contribution of the renin-angiotensin-aldosterone system (RAAS) to central nervous system (CNS) disorders is not yet fully understood. RAAS has been shown to be involved in the proliferation of astrocytes, which have a role in neuronal damage contributing to neurodegenerative diseases. However, the direct relationship between RAAS and neuronal damage is still unclear. We therefore examined the effect of angiotensin (Ang) II and aldosterone (Aldo) on damage to spinal ganglion neurons (SGNs) by regulating astrocytes. Ang II stimulation significantly increased DNA damage in SGNs in a time-dependent manner. This increase in DNA damage was further enhanced when SGNs were co-cultured with astrocytes. On the other hand, no significant increase was observed in SGNs co-cultured with astrocytes without Ang II stimulation. Moreover, the addition of conditioned medium from Ang II-treated astrocytes exacerbated SGN DNA damage. An Ang II type 1 receptor blocker, valsartan, inhibited Ang II-stimulated DNA damage but not DNA damage induced by conditioned medium prepared from astrocyte cultures. In contrast, an Aldo antagonist, eplerenone, significantly inhibited DNA damage induced by the culture medium from Ang II-treated astrocytes. Ang II-stimulated Aldo secretion in the conditioned medium from astrocytes. Furthermore, the administration of Aldo alone also enhanced DNA damage in SGNs. Finally, flow cytometric analysis showed that Ang II or Aldo treatment markedly increased the percentage of dead SGNs. In conclusion, Ang II-and Aldo-induced neuronal damage in SGNs through astrocytes regulation. Blocking Ang II and Aldo to target astrocytes might be useful for the treatment of CNS disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Angiotensin II and aldosterone-induced neuronal damage in neurons through an astrocyte-dependent mechanism

et al. 2011

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“…In the latter study, lower -344C allele frequency was linked with increased disease severity, which prompted speculation as to a possible protective nature of the -344C allele. 17 Another French study demonstrated that CYP11B2 TC and CC genotypes were associated with lower stroke index, 27 though not with blood pressure changes and gender-related contribution to C-344T effect was suggested. 27 These discrepancies may be explained by the difference in patient selection, evaluation of stroke severity, or ethnic differences.…”

Section: Regression Analysismentioning

confidence: 99%

“…26 A limited number of studies has addressed the contribution of CYP11B2 C-344T promoter variant to stroke pathogenesis, but with inconsistent findings. 17,27 The aim of the present case-control study was to examine whether C-344T CYP11B2 gene variant is associated with ischaemic stroke among Tunisians.…”

Section: Introductionmentioning

confidence: 99%

Aldosterone synthase gene (CYP11B2) promoter polymorphism as a risk factor for ischaemic stroke in Tunisian Arabs

Saidi

Mahjoub

Almawi

2010

J Renin Angiotensin Aldosterone Syst

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Introduction. We investigated the contribution of aldosterone synthase CYP11B2 polymorphism (C-344T) to the age-related changes in blood pressure in stroke patients. Subjects and methods. Study subjects comprised 329 stroke patients (121 normotensive, 208 hypertensive) and 444 healthy controls. Genotyping was done by PCR-RFLP, and the contribution of CYP11B2 polymorphism to the risk of stroke was analysed by regression analysis. Results. The T allele, and CT, TT, and CT + TT genotypes, independently of sex and age, were significantly associated with increased stroke risk. Varied distributions of CYP11B2 genotypes were noted among patients with respect to gender, age and hypertension status, being pronounced in hypertensive patients. Both systolic and diastolic blood pressure were positively correlated with the presence of T allele. Mean systolic and diastolic blood pressure were significantly higher among young (< 60 years) CT and TT genotype carriers. Regression analysis confirmed the positive association of CT and TT genotypes and systolic blood pressure, and the negative association of diastolic blood pressure with odds of stroke development. Taking normotensive patients as reference, regression analysis identified TT genotype, age and female gender to be independently associated with increased odds of stroke. Conclusion. Compared to CC genotype, CT and TT CYP11B2 genotypes are independently associated with increased stroke index.

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“…Patients presenting with SVD usually present in their later decades with often features suggestive of cognitive slowing, psychomotor withdrawal due to severe executive dysfunction described as difficulty to pay attention, retrieval defect, tip of the tongue phenomena, short term memory defects, and occasionally impaired judgement [16]. Gait and balance disturbances and falls are also major symptoms of patients with cerebral small vessel disease (SVD), and an important cause of morbidity and mortality in the elderly.…”

Section: Clinical Manifestationsmentioning

confidence: 99%

Cerebral Small Vessel Disease Clinical, Neuropsychological, and Radiological Phenotypes, Histopathological Correlates, and Described Genotypes: A Review

Issac

Chandra

Christopher

et al. 2015

Journal of Geriatrics

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Introduction. Vascular cognitive impairment is a common yet preventable cause for dementia. It needs high degree of suspicion and appropriate designing of investigatory tools to confirm diagnosis, identify comorbidities, and ascertain the areas of impairment. Commonly DSM-IV criterion is applied for diagnosis and detailed clinical and neuropsychological examination for identifying the specific phenotype is used. Early diagnosis using the mandatory criteria will help in early initiation of disease modifying treatment strategies which can result in partial reversal of vascular changes and arrest of progression. Patients with young onset disease might require genetic characterization for designing more aggressive treatment.Discussion and Conclusion. Dementias as such carry poor course and prognosis resulting in severe Disability Adjusted Life Years (DALYs) for patients and caregivers. Therefore, it is mandatory to identify treatable and preventable causes so that man power loss can be reduced.

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The renin-angiotensin-aldosterone system in cerebral small vessel disease

Abstract: This exploratory study found no strong evidence for RAAS involvement in severe SVD in this population. The whole spectrum of SVD, including EC, MLI, and LA, can be considered as phenotypes for genetic studies.

Cited by 29 publications

References 38 publications

Angiotensin II and aldosterone-induced neuronal damage in neurons through an astrocyte-dependent mechanism

Angiotensin II and aldosterone-induced neuronal damage in neurons through an astrocyte-dependent mechanism

Aldosterone synthase gene (CYP11B2) promoter polymorphism as a risk factor for ischaemic stroke in Tunisian Arabs

Cerebral Small Vessel Disease Clinical, Neuropsychological, and Radiological Phenotypes, Histopathological Correlates, and Described Genotypes: A Review

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