A Call for Rigorous Study of Statins in Resolution of Cerebral Cavernous Malformation Pathology

Eisa-Beygi, Shahram; Wen, Xiao‐Yan; Macdonald, R. Loch

doi:10.1161/strokeaha.114.005132

Cited by 21 publications

(9 citation statements)

References 38 publications

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“…10 Others have cautioned whether statins might have deleterious effects in light of broader signaling effects beyond ROCK inhibition. 36 Our results herein indeed suggest that CCM patients taking statins for routine cardiovascular indications have a trend of lower white matter permeability compared with those not on statins. However, statins did not seem to have an effect on the permeability of the CCM lesions themselves.…”

Section: Age and Vascular Permeability In Brain And Lesionssupporting

confidence: 65%

Vascular Permeability in Cerebral Cavernous Malformations

Mikati

Khanna

Zhang

et al. 2015

J Cereb Blood Flow Metab

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Patients with the familial form of cerebral cavernous malformations (CCMs) are haploinsufficient for the CCM1, CCM2, or CCM3 gene. Loss of corresponding CCM proteins increases RhoA kinase-mediated endothelial permeability in vitro, and in mouse brains in vivo. A prospective case-controlled observational study investigated whether the brains of human subjects with familial CCM show vascular hyperpermeability by dynamic contrast-enhanced quantitative perfusion magnetic resonance imaging, in comparison with CCM cases without familial disease, and whether lesional or brain vascular permeability correlates with CCM disease activity. Permeability in white matter far (WMF) from lesions was significantly greater in familial than in sporadic cases, but was similar in CCM lesions. Permeability in WMF increased with age in sporadic patients, but not in familial cases. Patients with more aggressive familial CCM disease had greater WMF permeability compared to those with milder disease phenotype, but similar lesion permeability. Subjects receiving statin medications for routine cardiovascular indications had a trend of lower WMF, but not lesion, permeability. This is the first demonstration of brain vascular hyperpermeability in humans with an autosomal dominant disease, as predicted mechanistically. Brain permeability, more than lesion permeability, may serve as a biomarker of CCM disease activity, and help calibrate potential drug therapy.

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Section: Age and Vascular Permeability In Brain And Lesionssupporting

confidence: 65%

Vascular Permeability in Cerebral Cavernous Malformations

Mikati

Khanna

Zhang

et al. 2015

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…However, we cannot conclude herein that statins are harmful in CCM merely because they may lower non-HDL cholesterol. The beneficial versus harmful effects of statins in CCM, and any relationship to lower levels of circulating lipids, remain speculative [38]. These questions are best addressed in hypothesis-driven laboratory studies and clinical trials specifically focused on CCM.…”

Section: Rock Activity In Leukocytes and Plasma Crp Activity Are Not Comentioning

confidence: 99%

Peripheral Plasma Vitamin D and Non-HDL Cholesterol Reflect the Severity of Cerebral Cavernous Malformation Disease

et al. 2016

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Aim: To correlate cerebral cavernous malformations (CCMs) disease aggressiveness with peripheral blood biomarkers hypothesized mechanistically. Patients & methods: A prospective case–control study enrolled 43 CCM patients, where 25-(OH) vitamin D, HDL and non-HDL cholesterol, CRP plasma levels and leukocyte ROCK activity were correlated with parameters of disease aggressiveness reflecting chronic and acute domains. Results: Patients with one or more features of chronically aggressive disease (early age at symptom onset, two or more symptomatic bleeds, high lesion burden) had significantly lower 25-(OH) vitamin D and non-HDL cholesterol levels in comparison to patients without these features. Conclusion: Validation of these biomarkers and their potential treatment modulation may influence the clinical care of patients with CCM disease.

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“…Nevertheless, the results of this preliminary investigation indicate that our dual modality technique could be an effective tool for assessing the effects of antiangiogenic drugs on zebrafish larvae. In the future we plan to assess the impact of higher I3M concentrations on both the anatomy and vasculature of developing wild type zebrafish, as well as investigate the effects of other drugs such as statins, which may be involved in vascular stability and intracerebral hemorrhages [ [43] , [44] , [45] ].…”

Section: Resultsmentioning

confidence: 99%