RESUMO
The phenotypic modulation of contractile vascular smooth muscle cell (VSMC) is widely accepted as the pivotal process in the arterial remodeling induced by hypertension. This study aimed to investigate the potential role of transient receptor potential vanilloid type 1 (TRPV1) on regulating VSMC plasticity and intracranial arteriole remodeling in hypertension. Spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) rats and TRPV1-/- mice on a C57BL/6J background were used. By microscopic observation of the histopathological sections of vessels from hypertensive SHR and age-matched normotensive WKY control rats, we found that hypertension induced arterial remodeling. Decreased α-smooth muscle actin (α-SMA) and SM22α while increased osteopontin (OPN) were observed in aorta and VSMCs derived from SHR compared with those in WKY, and VSMCs derived from SHR upregulated inflammatory factors. TRPV1 activation by capsaicin significantly increased expression of α-SMA and SM22α, reduced expression of OPN, retarded proliferative and migratory capacities and inhibited inflammatory status in VSMCs from SHR, which was counteracted by TRPV1 antagonist 5'-iodoresiniferatoxin (iRTX) combined with capsaicin. TRPV1 activation by capsaicin ameliorated intracranial arteriole remodeling in SHR and deoxycorticosterone acetate (DOCA)-salt hypertensive mice. However, the attenuation of arteriole remodeling by capsaicin was not observed in TRPV1-/- mice. Furthermore, TRPV1 activation significantly decreased the activity of PI3K and phosphorylation level of Akt in SHR-derived VSMCs. Taken together, we provide evidence that TRPV1 activation by capsaicin attenuates intracranial arteriole remodeling through inhibiting VSMC phenotypic modulation during hypertension, which may be at least partly attributed to the suppression PI3K/Akt signaling pathway. These findings highlight the prospect of TRPV1 in prevention and treatment of hypertension.
Assuntos
Arteríolas/metabolismo , Hipertensão/metabolismo , Modelos Biológicos , Músculo Liso Vascular/metabolismo , Canais de Cátion TRPV/metabolismo , Remodelação Vascular , Animais , Pressão Intracraniana , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Canais de Cátion TRPV/deficiênciaRESUMO
BACKGROUND: The association between methylenetetrahydrofolate reductase (MTHFR) gene A1298C polymorphism and adult stroke remains controversial. The present article was designed to clarify this relationship through pooled analysis of the numerous epidemiological studies focusing on this association. METHODS: We comprehensively searched all published papers in electronic database including PubMed, Embase, Web of Science, Chinese Biomedical Literature on disc (CBMdisc) and China National Knowledge Infrastructure (CNKI) up to 2013. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) for allelic (C allele vs. A allele), additive (CC vs. AA), dominant (CC+AC vs. AA), and recessive (CC vs. AA+AC) models were calculated. Subgroup and sensitivity analyses were performed to detect the heterogeneity and examine the reliability of results, respectively. Begg's funnel plots and Egger's regression test were used to assess the potential publication bias. RESULTS: A total of fifteen studies containing 2,361 cases and 2,653 controls were included in the final meta-analysis. The combined results of overall analysis showed that there was significant association between MTHFR gene A1298C polymorphism and adult stroke (allelic model: OR=1.36, 95% CI=1.11-1.67; additive model: OR=1.88, 95% CI=1.12-3.18; dominant model: OR=1.33, 95% CI=1.08-1.65 and recessive model: OR=1.77, 95% CI=1.07-2.94, respectively). On subgroup analysis by ethnicity of study population, significant association was shown in meta-analysis based on Asian population (allelic model: OR=1.40, 95% CI=1.19-1.65; additive model: OR=2.58, 95% CI=1.34-4.96; dominant model: OR=1.44, 95% CI=1.20-1.73 and recessive model: OR=2.12, 95% CI=1.20-3.76, respectively), but not in Caucasian population (allelic model: OR=1.30, 95% CI=0.93-1.82; additive model: OR=1.65, 95% CI=0.81-3.33; dominant model: OR=1.17, 95% CI=0.86-1.61 and recessive model: OR=1.70, 95% CI=0.83-3.50, respectively). In addition, the heterogeneity was effectively removed or decreased by limiting the included studies with population of Asian ethnicity. Furthermore, the corresponding pooled ORs were not materially changed in all genetic models of meta-analysis after limiting the included studies with population-based controls. However, except the recessive model, publication bias presented in the allelic, additive, dominant models identified by the Begg's funnel plots and Egger's regression test. CONCLUSIONS: In conclusion, the overall analysis suggests that MTHFR gene A1298C polymorphism plays an important role in the development of adult stroke. Genotype CC of MTHFR-1298A/C could increase the risk of stroke and may act as a predictor for clinical evaluation, especially in the Asian population. More studies with large-scale and different ethnicities are required to further confirm our findings.
Assuntos
Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Acidente Vascular Cerebral/genética , Adulto , Povo Asiático/genética , Predisposição Genética para Doença , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único , População Branca/genéticaRESUMO
INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) and intracerebral hemorrhage (ICH) are main forms of hemorrhagic stroke. Data regarding cerebral small vessel disease (SVD) burden and incidental small lesions on diffusion-weighted imaging (DWI) following aSAH are sparse. PATIENTS AND METHODS: We retrospectively analyzed a prospective cohort of aSAH and ICH patients with brain MRI within 30 days after onset from March 2015 to January 2023. White matter hyperintensity (WMH), lacune, perivascular space, cerebral microbleed (CMB), total SVD score, and incidental DWI lesions were assessed and compared between aSAH and ICH. Clinical and radiological characteristics associated with small DWI lesions in aSAH were investigated. RESULTS: We included 180 patients with aSAH (median age [IQR] 53 [47-61] years) and 299 with ICH (63 [53-73] years). DWI lesions were more common in aSAH than ICH (47.8% vs 14.4%, p < 0.001). Higher total SVD score was associated with ICH versus aSAH irrespective of hematoma location, whereas DWI lesions and strictly lobar CMBs were correlated with aSAH. Multivariable analysis showed that shorter time from onset to MRI, anterior circulation aneurysm rupture, CMB ⩾ 5, and total SVD score were associated with DWI lesions in aSAH. DISCUSSION AND CONCLUSION: Incidental DWI lesions and strictly lobar CMBs were more frequent in aSAH versus ICH whereas ICH had higher SVD burden. Incidental DWI lesions in aSAH were associated with multiple clinical and imaging factors. Longitudinal studies to investigate the dynamic change and prognostic value of the covert hemorrhagic and ischemic lesions in aSAH seem justified.
Assuntos
Hemorragia Cerebral , Doenças de Pequenos Vasos Cerebrais , Imagem de Difusão por Ressonância Magnética , Hemorragia Subaracnóidea , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/epidemiologia , Idoso , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Estudos Retrospectivos , Prevalência , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Doenças de Pequenos Vasos Cerebrais/complicações , Achados Incidentais , Estudos ProspectivosRESUMO
Hyperphosphorylated tau is an important pathological agent in Alzheimer's disease (AD). Tau effluxes from the brain to the blood could potentially stimulate the production of naturally occurring antibodies (NAbs). We aimed to investigate whether NAbs to tau (NAbs-tau) was generated in human blood and to figure out the alteration of plasma NAbs-tau level in AD patients. About 192 AD patients and 192 age-matched and non-demented controls (NC) were enrolled in the present study. Immunofluorescence staining and western blot assays were used to confirm the existence of NAbs-tau in human blood. The plasma level of NAbs-tau in NC and AD group was analyzed by ELISA. Immunofluorescence staining and western blot assays confirmed the existence of NAbs-tau in human blood. However, no significant difference in the plasma level of NAbs-tau was observed between NC and AD group. Furthermore, the plasma level of NAbs-tau had no significant correlation with MMSE scores. The present study confirmed that NAbs-tau exists in human blood but does not differ in level between the NC and AD group. Plasma NAbs-tau is not a reliable biomarker for AD.
Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico por imagem , Autoanticorpos/sangue , Proteínas tau/sangue , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Animais , Biomarcadores/sangue , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pessoa de Meia-IdadeRESUMO
The present study is to investigate whether diabetes mellitus (DM) increases risk of adverse long-term outcomes after intracranial stent placement. Patients receiving intracranial stenting were assigned to DM group and non-DM group according to diabetes status. The long-term follow-up endpoint was composite of any stroke and death within 30 days, any ischemic stroke beyond 30 days, and transient ischemic attack in the territory of the stented artery at any time. A total of 44 stenoses in 43 patients were retrospectively analyzed. The cumulative probability of the composite outcomes were 15.4% (95% CI 15.3-47.3%) at 1 year and 30.8% (95% CI 26.5-33.6%) at 2 years for DM group; 17.5% (95% CI 16.0-31.2%) at both 1 year and 2 years for non-DM group (log-rank test, P = 0.424). After adjusting for the confounders, the risk of DM versus non-DM for composite outcomes remained insignificant (hazard ratio: 2.84, 95% CI 0.46-17.66; P = 0.26). Our results showed that there is no significant difference between patients with DM and without DM in cumulative probability of the composite outcomes. It suggests that based on our data, there is no evidence that DM increases the risk of adverse long-term outcomes after intracranial stent placement.
Assuntos
Complicações do Diabetes/terapia , Stents/efeitos adversos , Constrição Patológica/complicações , Complicações do Diabetes/complicações , Feminino , Humanos , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco , Fatores de TempoRESUMO
Plasma amino acids levels were measured in first-onset treatment-naïve depressed patients (n=26) and healthy controls (n=25) using a mass spectrometry-based method. One of the major findings was that a logistic regression model constructed from tryptophan, glutamine and cysteine discriminated depressed subjects from controls with a receiver-operating-characteristic curve integral of 0.90.