Evaluation of Asymmetric Dimethylarginine and Homocysteine in Microangiopathy-Related Cerebral Damage

Notsu, Yoshitomo; Nabika, Toru; Bokura, Hirokazu; Suyama, Yoji; Kobayashi, Shotai; Yamaguchi, Schuhei; Masuda, Junichi

doi:10.1038/ajh.2008.346

Cited by 31 publications

(30 citation statements)

References 47 publications

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“…In CHF, elevated levels of ADMA concurred with disease severity, and ADMA was suggested as a pathological link for impaired vasodilator capacity [31]. In acute stroke, increased ADMA levels were observed in cardioembolic infarctions, transient ischemic attacks and microangiopathy-related cerebral damage [9,32]. In our study, patients with cardioembolic ischemic stroke displayed elevated ADMA levels as well as diminished L -arginine/ADMA ratios that were associated with reduced vasodilatation.…”

Section: Discussionmentioning

confidence: 83%

“…Elevation of plasma ADMA concentration and a decreased L -arginine/ADMA ratio correlate with endothelial-dependent flow-mediated dilatation (FMD) in hypercholesterolemia, hyperhomocysteinemia and hypertriglyceridemia [7,8]. In cerebrovascular research, an independent association of the L -arginine/ADMA ratio with microangiopathy-related cerebral damage was shown in 712 patients [9]. …”

Section: Introductionmentioning

confidence: 99%

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Endothelial Dysfunction of the Peripheral Vascular Bed in the Acute Phase after Ischemic Stroke

Scherbakov¹,

Sandek

Martens‐Lobenhoffer

et al. 2011

Cerebrovasc Dis

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Background: Endothelial dysfunction (ED) is relevant for the development of cerebrovascular and cardiovascular diseases. Asymmetric dimethylarginine (ADMA) competes with L-arginine and has been implicated in the development of ED. Increased levels of ADMA have been found in chronic heart failure (CHF). We hypothesized that peripheral ED in acute ischemic stroke is associated with increased ADMA levels. Methods: We evaluated 60 patients with acute stroke in the territory of the middle cerebral artery. Stroke patients were classified according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. We compared these patients with patients of similar age without known cardiovascular disease (negative controls, n = 23) and patients with stable, ambulatorily treated CHF (n = 46, left ventricular ejection fraction = 33.8 ± 10.9) with known ED (positive controls). Peripheral endothelial function was assessed by EndoPAT2000 technology using the reactive hyperemia index (RHI). Results: RHI was significantly decreased in stroke and in CHF compared to controls (1.8 ± 0.3 vs. 1.8 ± 0.4 vs. 2.2 ± 0.4, respectively, ANOVA p = 0.01). A decreased RHI was observed in cardioembolic and lacunar infarcts and stroke of undetermined etiology (1.7 ± 0.4, 1.8 ± 0.5 and 1.7 ± 0.3, p < 0.0001). The L-arginine/ADMA ratio was significantly decreased in stroke and in CHF (147.6 ± 31.7 and 126.1 ± 37.9 vs. controls: 161.5 ± 26.1, p < 0.0001) and was lowest in stroke patients in the cardioembolic group (133.0 ± 29.4, p < 0.0001). A lower L-arginine/ADMA ratio was associated with ED in cardioembolic stroke and CHF (r = 0.324, p < 0.05 and r = 0.429, p < 0.0001). Conclusion: Peripheral ED occurs to a similar degree in acute ischemic stroke and CHF. The impaired vasodilator capacity of peripheral arteries reflects the TOAST classification. ADMA may play a role in ED in both acute ischemic stroke and CHF.

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Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Endothelial Dysfunction of the Peripheral Vascular Bed in the Acute Phase after Ischemic Stroke

Scherbakov¹,

Sandek

Martens‐Lobenhoffer

et al. 2011

Cerebrovasc Dis

View full text Add to dashboard Cite

show abstract

“…Such low L-arginine/ ADMA ratio is associated with lacunar infarctions in patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). 51,52 Interestingly, we observed a transient elevation of the L-arginine/ADMA ratio at 24 poststroke hours suggesting that a temporary increase of L-arginine along with decrease of ADMA might be a protective mechanism. It has been shown previously that ADMA increased vascular stiffness and decreased cerebral perfusion in healthy subjects.…”

Section: Discussionmentioning

confidence: 85%

The L-arginine Pathway in Acute Ischemic Stroke and Severe Carotid Stenosis: Temporal Profiles and Association with Biomarkers and Outcome

Molnár¹,

Pusch²,

Papp³

et al. 2014

Journal of Stroke and Cerebrovascular Diseases

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“…49,73 In all the studies in which ADMA levels were measured, an independent association with both lacunar infarcts and WMH was reported. 54,55,78 Matrix metalloproteinase 9 (MMP9) was measured in a total of 234 patients, but the association with WMH was significant only at univariate analyses. 69,70 The Northern Manhattan Study found an independent association of both MPO and Lp-PLA2 with WMH, but the result for Lp-PLA2 was not confirmed in the Framingham Offspring Study.…”

Section: 61mentioning

confidence: 99%

Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review

Poggesi

Pasi

Pescini

et al. 2015

J Cereb Blood Flow Metab

220

183

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The term cerebral small vessel disease (SVD) refers to a group of pathologic processes with various etiologies that affect small arteries, arterioles, venules, and capillaries of the brain. Magnetic resonance imaging (MRI) correlates of SVD are lacunes, recent small subcortical infarcts, white-matter hyperintensities, enlarged perivascular spaces, microbleeds, and brain atrophy. Endothelial dysfunction is thought to have a role in the mechanisms leading to SVD-related brain changes, and the study of endothelial dysfunction has been proposed as an important step for a better comprehension of cerebral SVD. Among available methods to assess endothelial function in vivo, measurement of molecules of endothelial origin in peripheral blood is currently receiving selective attention. These molecules include products of endothelial cells that change when the endothelium is activated, as well as molecules that reflect endothelial damage and repair. This review examines the main molecular factors involved in both endothelial function and dysfunction, and the evidence linking endothelial dysfunction with cerebral SVD, and gives an overview of clinical studies that have investigated the possible association between endothelial circulating biomarkers and SVD-related brain changes. KeywordsCerebral small vessel disease, endothelium, inflammation, lacunar infarcts, white-mater hyperintensities The term cerebral small vessel disease (SVD) refers to a group of pathologic processes with various etiologies that affect the small arteries, arterioles, venules, and capillaries of the brain.1 Age/hypertension-related SVDs and cerebral amyloid angiopathy are the most common sporadic forms of SVD. Among a few genetic forms of SVD, CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), caused by NOTCH3 gene mutations, is the most frequent one. It is a systemic arteriopathy although the clinical symptoms are those caused by brain dysfunction. The effects of both sporadic and inherited SVD on the brain parenchyma are represented by lesions mainly located in the subcortical structures, and include lacunar infarcts, ischemic white-matter lesions, and intracerebral hemorrhage. An international working group has recently published the STRIVE (STandards for ReportIng Vascular changes on nEuroimaging) to provide definitions and imaging standards for markers and consequences of SVD.2 According to this consensus, changes currently seen on neuroimaging related to SVD include lacunes, recent small subcortical infarcts, white-matter hyperintensities (WMH), perivascular spaces (PVS), microbleeds (MB), and brain atrophy.Over the last few decades, evidence has being accumulated regarding prevalence, clinical significance, and

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Evaluation of Asymmetric Dimethylarginine and Homocysteine in Microangiopathy-Related Cerebral Damage

Abstract: ADMA and tHcy levels were studied in 712 subjects with or without MARCD. The Arg/ADMA ratio was suggested to be an independent risk factor for MARCD. A large-scale prospective study is warranted to confirm the causal relationship between Arg/ADMA and MARCD.

Cited by 31 publications

References 47 publications

Endothelial Dysfunction of the Peripheral Vascular Bed in the Acute Phase after Ischemic Stroke

Endothelial Dysfunction of the Peripheral Vascular Bed in the Acute Phase after Ischemic Stroke

The L-arginine Pathway in Acute Ischemic Stroke and Severe Carotid Stenosis: Temporal Profiles and Association with Biomarkers and Outcome

Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review

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