Logistic regression analysis of serum ALP in the presence of SLI and MS-cWMH.

<p>Logistic regression analysis of serum ALP in the presence of SLI and MS-cWMH.</p

Spline curves of the relationship between ALP level and the presence of SLI and MS-cWMH†.

<p>(A) Relationship between ALP level and SLI. (B) Relationship between ALP level and MS-cWMH. The black lines and gray shadows represent the estimated probability and 95% confidence intervals for the presence of SLI and MS-cWMH, and were drawn using the generalized additive model. The x-axis is limited from the 1^th to 99^th percentile of ALP. †Adjusted for age, gender, hypertension, diabetes, hyperlipidemia, coronary artery occlusive disease, and smoking. ALP: Alkaline phosphatase; SLI, silent lacunar infarct; MS-cWMH, moderate-to-severe cerebral white matter hyperintensities.</p

Association between Serum Alkaline Phosphatase Level and Cerebral Small Vessel Disease

<div><p>Background</p><p>Serum alkaline phosphatase (ALP) is a marker of vascular calcification. A high serum ALP level is associated with an increase in cardiovascular events, and predicts poor functional outcome in patients with stroke. We investigated whether serum ALP was associated with cerebral small vessel disease (cSVD) and large cerebral artery stenosis (LCAS).</p><p>Methods</p><p>We evaluated vascular risk factors, brain magnetic resonance images (MRIs), and MR angiograms from 1,011 neurologically healthy participants. The presence of silent lacunar infarction (SLI) and moderate-to-severe cerebral white matter hyperintensities (MS-cWMH) were evaluated as indices of cSVD on brain MRIs. Findings of extracranial arterial stenosis (ECAS) or intracranial arterial stenosis (ICAS) were considered to be indices of LCAS on MR angiograms.</p><p>Results</p><p>Subjects with SLI (odds ratio [OR]: 2.09; 95% confidence interval [CI]: 1.27–3.42; <i>p</i> = 0.004) and MS-cWMH (OR: 1.48; 95% CI; 1.03–2.13, <i>p</i> = 0.036) were significantly more likely to have ALP levels in the third tertile (ALP ≥ 195 IU/L) than the first tertile (ALP ≤ 155 IU/L), after adjusting for cardiovascular risk factors. The mean serum ALP level was significantly higher in patients with SLI or MS-cWMH compared to patients without those findings. After adjustment for confounding factors, the multivariate model found that the statistical significance of serum ALP remained when the presence of SLI (OR: 1.05 per 10 IU/L increase in ALP; 95% CI: 1.02–1.08; <i>p</i> = 0.003) or MS-cWMH (OR: 1.03 per 10 IU/L increase in ALP; 95% CI: 1.00–1.06; <i>p</i> = 0.025) were added to the model. There were no differences in the proportions of patients with LCAS, ICAS, and ECAS across the serum ALP tertiles.</p><p>Conclusions</p><p>Our study of neurologically healthy participants found a positive association between serum ALP level and indicators of cSVD, but no association between serum ALP level and the indicators of LCAS.</p></div

Mean concentration of serum ALP in participants with SLI and MS-cWMH.

<p>(A) Serum ALP levels between SLI and no SLI groups. (B) Serum ALP levels between four cWMH groups according to Fazekas score. Error bar indicates standard deviation. * <i>p</i> < 0.05. ALP: Alkaline phosphatase; SLI, silent lacunar infarct; MS-cWMH, moderate-to-severe cerebral white matter hyperintensities.</p

Logistic regression analysis of the presence of SLI, MS-cWMH, LCAS, ICAS, and ECAS in 1,011 Korean participants according to serum ALP tertile.

<p>Logistic regression analysis of the presence of SLI, MS-cWMH, LCAS, ICAS, and ECAS in 1,011 Korean participants according to serum ALP tertile.</p

Demographic and laboratory data of 1,011 study participants according to serum ALP tertile.

<p>Demographic and laboratory data of 1,011 study participants according to serum ALP tertile.</p

Analysis of the hybridization ability of miR-200a-MBs to ZEB1 mRNA using real-time PCR and immunostaining.

<p>(A) The illustration represents the binding sites of the primers used in real-time PCR. Real-time PCR analysis showed reduced expression levels of ZEB1 mRNA in miR-200a-MB-MNPs delivered NMuMG cells compared to the cells with scrambled-MB-MNPs. ** indicates p<0.01. (B) The localization of miR-200a-MBs and the RISC subunit Ago-2 were observed within the several regions of TGF-β1 treated cell. The Cy5 signals (yellow arrows) of miR-200a-MBs were in close proximity to the Alexa-546 signals of Ago-2 (white arrows). Small boxes were marked with a & b for the indication of the magnified regions. Scale bar, 10 µm.</p

Validation of miR-200a-MB-MNPs as an EMT imaging probe.

<p>(A) miR-200a-MB-MNPs were introduced into NMuMG cells at 0, 2, 6, and 12 hours post-TGF-β1 treatment. Cy5 fluorescence (pink) was observed at 2 hours after TGF-β1 treatment, and the Cy5 signals increased in a time-dependent manner. (B) Cy5 signals were analyzed in either miR-200a-MB-MNPs or scrambled-MB-MNPs delivered NMuMG cells after 6 hours of TGF-β1 treatment. Immunostaining of ZEB1 was performed to confirm the mesenchymal transformation of NMuMG into mesenchymal phenotype. Scale bar, 10 µm.</p

Clinical characteristics of participants according to the red blood cell distribution width.

<p>Clinical characteristics of participants according to the red blood cell distribution width.</p

Subgroup analysis for the effect of RDW on severe-degree of leukoaraiosis.

<p>Subgroup analysis for the effect of RDW on severe-degree of leukoaraiosis.</p