The Role of Cystatin C in Cerebral Amyloid Angiopathy and Stroke: Cell Biology and Animal Models

Levy, Efrat; Jaskólski, Mariusz; Grubb, Anders

doi:10.1111/j.1750-3639.2006.tb00562.x

Cited by 94 publications

(88 citation statements)

References 164 publications

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“…In our data, we find that circulating levels of serine are significantly associated with lower PWV and with expression levels of a probe on the cystatin-like 1 ( CSTL1) gene on chromosome 20 (Beta = 0.09, SE = 0.02, P = 4.26 × 10 −8 ). The cystatin locus on chromosome 20 contains the majority of the type 2 cystatin genes and pseudogenes, and has been associated with cerebral haemorrhage and cerebritis [23]. …”

Section: Resultsmentioning

confidence: 99%

Metabolomic study of carotid–femoral pulse-wave velocity in women

Menni¹,

Mangino²,

Cecelja

et al. 2015

Journal of Hypertension

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Objective:Carotid–femoral pulse-wave velocity (PWV) is a measure of aortic stiffness that is strongly associated with increased risk of cardiovascular morbidity and mortality. The aim of the current study was to identify the molecular markers and the pathways involved in differences in PWV in women, in order to further understand the regulation of arterial stiffening.Methods:A total of 280 known metabolites were measured in 1797 female twins (age range: 18–84 years) not on any antihypertensive medication. Metabolites associated with PWV (after adjustment for age, BMI, metabolite batch, and family relatedness) were entered into a backward linear regression. Transcriptomic analyses were further performed on the top compounds identified.Results:Twelve metabolites were associated with PWV (P < 1.8 × 10−4). One of the most strongly associated metabolites was uridine, which was not associated with blood pressure (BP) and traditional risk factors but correlated significantly with the gene-expression levels of the purinergic receptor P2RY2 (Beta = −0.010, SE = 0.003, P = 0.007), suggesting that it may play a role in regulating endothelial nitric oxide synthase phosphorylation. On the other hand, phenylacetylglutamine was strongly associated with both PWV and BP.Conclusion:Circulating levels of uridine, phenylacetylglutamine, and serine appear strongly correlated with PWV in women.

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Section: Resultsmentioning

confidence: 99%

Metabolomic study of carotid–femoral pulse-wave velocity in women

Menni¹,

Mangino²,

Cecelja

et al. 2015

Journal of Hypertension

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“…For these pathologies, it is important to characterize not only the mechanisms that control cystatin C expression but also those that regulate its dimerization. However, most of the studies that have examined cystatin C dimerization were based on in vitro assays employing recombinant protein; little is known about the generation of dimers in vivo (18).…”

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confidence: 99%

Developmental Regulation of Synthesis and Dimerization of the Amyloidogenic Protease Inhibitor Cystatin C in the Hematopoietic System

Xu¹,

Lindemann

Vega-Ramos

et al. 2014

Journal of Biological Chemistry

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Background: Dimerization of cystatin C initiates formation of amyloid fibrils in vascular walls. Results: Reactive oxygen species regulate cystatin C dimerization in cells of the hematopoietic system, which are major contributors to the total pool of circulating cystatin C. Conclusion: Cystatin C dimerization is regulated in hematopoietic cells. Significance: Cystatin C synthesis and dimerization might be manipulated for therapeutic gain.

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“…More than 90% of the total body CysC content is distributed in the CSF, with a negligible plasma-derived fraction. 18 Results from previous studies indicate that CysC plays a role in neurological disorders involving amyloid, such as Alzheimer disease, 19 cerebral amyloid angiopathy, 20 and multiple sclerosis. 21 Prior studies have also evaluated the association of intrathecal CysC with pain.…”

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confidence: 99%