Characteristic Features of <i>in vivo</i> Skin Microvascular Reactivity in CADASIL

Gobron, C.; Vahedi, Katayoun; Vicaut, Éric; Stücker, Olivier; Laemmel, Elisabeth; Baudry, Nathalie; Bousser, Marie Germaine; Chabriat, Hugues

doi:10.1038/sj.jcbfm.9600356

Cited by 28 publications

(29 citation statements)

References 27 publications

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“…Vasodilation of a conduit vessel, the brachial artery, was similar in patients and controls, which is also in agreement with a previous study. 20 However, the present study showed a reduction in both resting and hyperemic forearm blood flow in the forearm of CADASIL patients compared with the controls. This difference in hyperemic blood flow was only significant for the highest dose of acetylcholine.…”

Section: Discussioncontrasting

confidence: 42%

Impaired Endothelial Function of Forearm Resistance Arteries in CADASIL Patients

Stenborg

Kalimo

Viitanen

et al. 2007

Stroke

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Background and Purpose-Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary arteriopathy, which mainly involves the brain causing stroke and dementia. Mice expressing the mutated protein display early dysfunction in vasoreactivity in resistance arteries, but studies of patients have been inconclusive so far. Methods-We examined peripheral endothelium-dependent vasodilatation in 10 CADASIL-patients and 20 controls using 3 methods: venous occlusion plethysmography of forearm blood flow with intraarterial acetylcholine and sodium nitroprusside infusions for evaluation of resistance arteries, ultrasound with flow mediated vasodilatation (FMD) of the brachial artery for evaluation of a conduit artery, and the pulse wave method with measurements before and after terbutaline for evaluation of systemic endothelium-dependent vasodilation. Results-The CADASIL patients displayed reductions in both basal (Pϭ0.034) and stimulated blood flow (Pϭ0.023 for the highest dose of acetylcholine) and an impaired endothelium-dependent vasodilation when investigated in forearm resistance arteries (Pϭ0.019). The FMD and the pulse wave method did not show any reduction in endotheliumdependent vasodilation in the patients. Conclusions-Endothelium-dependent vasodilation was impaired in resistance arteries, but not in a conduit artery, in the forearm of CADASIL patients.

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Section: Discussioncontrasting

confidence: 42%

Impaired Endothelial Function of Forearm Resistance Arteries in CADASIL Patients

Stenborg

Kalimo

Viitanen

et al. 2007

Stroke

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“…Experimental studies revealed that in response to mechanical stress VSMC synthesizes abundant amount of matrix proteins, mostly collagen [6]. Since in CADASIL mechano reactivity of vessels is disturbed [7][8][9], it is possible that normal levels of vascular tension can be interpreted by VSMC as too high and, like in the case of arterial hypertension, it can initiate cascade of reactions leading to vessel fibrosis. It is known that collagen stimulates phenotypic changes in VSMC towards the synthetic phenotype [10] more vulnerable for apoptosis [11] especially when VSMC are submitted to mechanical stress [12].…”

Section: Discussionmentioning

confidence: 99%

Changes in the Vascular Extracellular Matrix as a Potential Cause of Myocyte Loss via Anoikis in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

Dziewulska¹,

Nycz²,

Rajczewska-Oleszkiewicz³

2017

J Clin Exp Pathol

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Objective: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a generalized vasculopathy caused by mutations in the NOTCH3 gene, leading to degeneration and loss of vascular smooth muscle cells (VSMC). The relationship between NOTCH 3 mutations and VSMC death is unknown. One possible cause of myocyte deficit may be anoikis, a special type of apoptosis due to loss or inappropriate cell adhesion to extracellular matrix. Method:To verify this hypothesis we examined immune expression of main compounds of vascular extracellular matrix (laminin, fibronectin and collagen IV) and selected metallo proteinases (MMP-2, MMP-3, and MMP-9) in cerebral, skin and skeletal muscle arterial vessels in autopsy material and biopsy specimens of CADASIL patients. Results:The immmune reactions revealed decreased expression of laminin and increased expression of collagen IV and fibronectin in arterial vessels. Moderately intense immune reactivity to MMP-9 and MMP-2 was present while immune reactivity to MMP-3 was absent. Conclusion:Quantitative and qualitative changes in vascular extracellular matrix found in CADASIL vessels may lead to VSMC loss via anoikis pathway.

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“…Skin vasoreactivity is altered in disease. For instance, the kinetics of reactive hyperemia after cuff occlusion displays a delayed and slow curve 17 . Endothelium-dependent vasodilation is impaired in resistance arteries (not conductive ones) in the forearm of patients 18 .…”

Section: Genetics and Pathogenesismentioning

confidence: 99%

CADASIL: pathogenesis, clinical and radiological findings and treatment

André

2010

Arq. Neuro-Psiquiatr.

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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common genetic cause of ischemic strokes and a most important model for the study of subcortical vascular dementia. This unrelentlessly progressive disease affects many hundreds of families all over the world but is not well studied in Brazil. This manuscript reviews pathogenetic, clinical, radiological and therapeutic features of CADASIL. The causal mutations are now very well known, but the same can not be said about its intimate pathogenetic mechanisms. The variable clinical presentation should lead physicians to actively pursue the diagnosis in many settings and to more thouroughly investigate family history in first degree relatives. A rational approach to genetic testing is however needed. Treatment of CADASIL is still largely empiric. Highquality therapeutic studies involving medications and cognitive interventions are strongly needed in CADASIL. Key words: CADASIL, etiology, genetics, diagnosis, therapeutics.cADAsIL: patogênese, achados clínicos e radiológicos e tratamento resumo CADASIL é a causa genética mais freqüente de infartos cerebrais e constitui modelo importante de estudo de demências vasculares subcorticais. De natureza inexoravelmente progressiva, afeta milhares de pessoas em todo o mundo. Sua importância é pouco reconhecida entre nós, o que nos levou à presente revisão dos principais aspectos patogenéticos, clínicos, neuroradiológicos e terapêuticos da doença. As mutações causais são hoje bem conhecidas, mas os mecanismos patogenéticos íntimos ainda permanecem misteriosos. A apresentação clínica variável deve fazer com que os médicos considerem o diagnóstico em vários contextos clínicos e investiguem de forma mais extensa que o usual a história familial deparentes de primeiro grau. Além disso, uma abordagem racional é necessária para reduzir custos e aumentar a eficiência do diagnóstico genético. O tratamento atual de pacientes com CADASIL é basicamente empírico. Estudos clínicos sobre medicamentos e intervenções cognitivas de alto nível metodológico constituem uma necessidade urgente.

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Characteristic Features of in vivo Skin Microvascular Reactivity in CADASIL

Cited by 28 publications

References 27 publications

Impaired Endothelial Function of Forearm Resistance Arteries in CADASIL Patients

Impaired Endothelial Function of Forearm Resistance Arteries in CADASIL Patients

Changes in the Vascular Extracellular Matrix as a Potential Cause of Myocyte Loss via Anoikis in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

CADASIL: pathogenesis, clinical and radiological findings and treatment

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