Advanced Glycation End Products Induce Atherosclerosis via RAGE/TLR4 Signaling Mediated-M1 Macrophage Polarization-Dependent Vascular Smooth Muscle Cell Phenotypic Conversion

Objective. The objective of this study was to investigate the involved mechanisms of advanced glycation end product- (AGE-) exacerbated atherosclerosis (AS). Methods. Toll-like receptor 4 (TLR4) inhibitor was administrated to type 2 diabetes mellitus (T2DM) AS rats. Atherosclerotic plaque, M1 macrophage infiltration, and VSMCs phenotypes were evaluated. AGE-exposed primary macrophages were treated with specific siRNAs knocking down receptor for AGEs (RAGE) and TLR4. Phenotypes of M1 macrophage and VSMCs were identified by fluorescent stains. Contact and noncontact coculture models were established. VSMCs and macrophages were cocultured in these models. ELISA was used to detect inflammatory cytokine concentrations. Relative mRNA expression levels were determined by real-time PCR. Relative protein expression and phosphorylation levels were evaluated by Western blots assays. Results. TLR4 inhibitor treatment significantly reduced arterial stenosis, infiltration of M1 polarized macrophages, and contractile-to-synthetic phenotype conversion of VSMCs in DM AS animals. RAGE and TLR4 silencing dramatically reduced AGE-induced macrophage M1 polarization, inflammatory cytokine secretion, and RAGE/TLR4/forkhead box protein C2 (FOXC2)/signaling which inhibited delta-like ligand 4 (Dll4) expression in macrophages. AGE-treated macrophages induced VSMC phenotypic conversion via activating Notch pathway in a contact coculture model rather than a noncontact model. The VSMC phenotypic conversion induction capability of macrophages was attenuated by RAGE and TLR4 silencing. Conclusions. AGEs induced activation of RAGE/TLR4/FOXC2 signaling, which featured macrophage with Dll4 high expression during M1 polarization. These macrophages promoted contractile-synthetic phenotypic conversion of VSMCs through the Dll4/Notch pathway after direct cell-to-cell contacts.

Prevalence and Risk Factors Comparison of Anterior and Posterior Intracranial Arterial Stenosis

The prevalence and risk factors of intracranial atherosclerotic stenosis (ICAS) located in the anterior circulation (AC) and posterior circulation (PC) has been scarcely noted in the general population. We aimed to determine ICAS prevalence and risk factor profile of AC and PC in a representative population. Data were from the China Hypertension Survey of Beijing. In total, 4800 people aged 35 years or older were enrolled in this subsurvey for ICAS, and 3954 participants were eligible for analysis. ICAS was assessed by transcranial Doppler. The prevalence of ICAS in AC was much greater than that in PC (11.9% vs. 4.2%), and subjects with ICAS in PC were 3.9 years older than those with ICAS in AC. Multivariable logistics regression showed that the odds of hypertension and diabetes increased by 79% (OR: 1.79, 95% CI: 1.40–2.27) and 35% (OR: 1.35, 95% CI: 1.04–1.75) in those with AC vascular lesions and by 3.35 times (OR: 3.35, 95% CI: 2.49–4.50) and 71% (OR: 1.71, 95% CI: 1.19–2.46) in those with PC vascular lesions compared with those without vascular lesions. Most modifiable vascular risk factors for ICAS appeared to exert similar magnitudes of risk for PC to AC lesions.

Predictors of preoperative cognitive dysfunction in adults with Moyamoya disease: a preliminary research

Objective To explore potential risk factors of preoperative cognitive dysfunction in adult patients with moyamoya disease (MMD) and discuss significance of moyamoya vessels. Methods The author reviewed adult MMD patients harboring no parenchymal infarction or hemorrhage underwent a standardized neuropsychological assessment test battery from December 2018 to May 2019. The authors defined patients with cognitive dysfunction as cognitive impairment shown on 3 or more neuropsychological tests. According to the presence of cerebral angiography, arterial stenosis, moyamoya vessels, and compensatory arteries were conducted. Univariate and multivariate analyses were performed to identify predictors for cognitive dysfunction before surgery. Subgroup analyses by onset type and Suzuki stage were carried out to identify specific predictors for preoperative cognitive dysfunction. Results In total, 29 of 92 (31.52%) patients had cognitive dysfunction. Multivariate analysis showed that moyamoya vessels generating from left hemisphere was recognized as independent predictor for cognitive dysfunction (P = 0.025, OR [95%CI], 0.085 [0.012–0.874]). For patients in left ICA-moyamoya subgroup, 19 of 45 (42.22%) cases with sparse moyamoya vessels had cognitive dysfunction (P = 0.031), while 22 (91.67%) of patients with dense moyamoya vessels had normal cognition (P = 0.004). Moyamoya vessels arising from ophthalmic artery had no significant association with cognitive dysfunction (P = 0.111). Multivariate analysis found that moyamoya vessels originating from left ICA was recognized as independent predictors for preoperative cognitive dysfunction (P = 0.048, OR [95%CI], 0.394 [0.132–0.926]). Conclusions Moyamoya vessels arising from left hemisphere was a risk factor for the preoperative cognitive dysfunction in adult patients with MMD, with the denser moyamoya vessels, the less cognitive dysfunction. The current study offers a new perspective of moyamoya vessels and supporting data for choosing MMD candidates on cerebral revascularization.

Angiographic Therapies for Diabetic Foot Syndrome

Background. The study aimed to improve treatment outcomes in diabetic foot syndrome patients by use of invasive pressure monitoring during arterial radiological interventions.Materials and methods. A total of 36 patients with type 2 diabetes and purulent necrotic lesions of lower extremities have been treated at the surgery unit of Bashkir State Medical University Clinic during 2019—2020, with 12 persons forming the main cohort and receiving the measures complemented with the newly developed “X-ray endovascular intraoperative significance evaluation of lower limb arterial stenosis” technique (Patent RU 2737215 of 26.11.2020). The control cohort comprised 24 patients following pertinent standard treatment and recommendations in this pathology.Results and discussion. Immediate treatment outcomes were evaluated by person in the main and control cohorts. Longterm outcomes were observed at 6, 12 and 24 months since hospital discharge in 10 (83.3 %) patients of the main and 19 (79.2 %) — of the control cohort. In a 2-year run, the limb was kept in 8 (66.7 %) patients having the new revascularisation technique and in 10 (41.7 %) persons of the control cohort (p < 0.05).Conclusion. The use of endovascular radiology for limb revascularisation and intraoperative significance monitoring of lower limb arterial stenosis allow the volume determination of balloon angioplasty and statement of revascularisation completeness.

Fluid-Attenuated Inversion Recovery Vascular Hyperintensity in Cerebrovascular Disease: A Review for Radiologists and Clinicians

Neuroradiological methods play important roles in neurology, especially in cerebrovascular diseases. Fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) is frequently encountered in patients with acute ischemic stroke and significant intracranial arterial stenosis or occlusion. The mechanisms underlying this phenomenon and the clinical implications of FVH have been a matter of debate. FVH is associated with large-vessel occlusion or severe stenosis, as well as impaired hemodynamics. Possible explanations suggested for its appearance include stationary blood and slow antegrade or retrograde filling of the leptomeningeal collateral circulation. However, the prognostic value of the presence of FVH has been controversial. FVH can also be observed in patients with transient ischemic attack (TIA), which may have different pathomechanisms. Its presence can help clinicians to identify patients who have a higher risk of stroke after TIA. In this review article, we aim to describe the mechanism and influencing factors of FVH, as well as its clinical significance in patients with cerebrovascular disease.

Correlations of myocardial bridges with left ventricle myocardial hypertrophy and prepontin coronary atherosclerosis

Background: Of particular interest are the studies researching the correlations of myocardial bridges with hypertrophic cardiomyopathy and correlations of thick myocardial bridges with the development of coronary atherosclerosis in the proximal to the bridge arterial part. Material and methods: Assessment of the correlation between myocardial bridges, coronary atherosclerosis, and the degree of hypertrophy of the left ventricle was performed by retrospective analysis of 6168 coronary angiography protocols (2012-2019) and echocardiographic data from patients’ clinical records. Results: Moderate systolic compression predominated, and the number of patients detected with severe under the bridge systolic coronary stenosis was double as in patients with nonsignificant coronary atherosclerosis. From the total number, patients with myocardial hypertrophy and myocardial bridges were twice less when compared with the patients with the normal myocardial thickness. The comparative research did not show any interdependence between the degree of vascular compression and the degree of left ventricular myocardial hypertrophy. Proximal to the bridges atherosclerosis was detected in 32% of cases without correlation with the force of the myocardial bridge. Conclusions: The study showed the absence of the correlation between the degree of arterial stenosis caused by the bridge and the degree of hypertrophy of the ventricular myocardium as well as the degree of proximal to the bridge atherosclerosis. Important finding was that the degree of coronary systolic compression is higher in patients with moderate and severe proximal to the bridge atherosclerosis.

On the issue of critical arterial stenosis

Cardiovascular disease (CVD) is the leading cause of death worldwide. The main contribution to the structure of mortality from CVD is made by atherosclerosis. Indications for surgical treatment of patients with diseases caused by atherosclerotic lesions of the arteries are set taking into account the degree of their stenosis. Angiography has been considered the gold standard for screening patients with CVD for many years. Numerous studies carried out over the past several decades have revealed the weak side of this method in assessing the significance of borderline stenosis. Therefore, to analyze such changes, functional tests were introduced to clarify the indications for surgical intervention. Currently, criteria for the significance of stenosis of the iliac, renal and coronary arteries have been determined. The significance of stenosis of the arteries supplying the brain and intestines is still a matter of debate and requires further study.

Unilateral Thalamic Infarction Associated with Rupture of Dissecting Posterior Cerebral Artery in Childhood-Onset Systemic Lupus Erythematosus: A Case Report

BackgroundCerebrovascular diseases are well-known complications of systemic lupus erythematosus (SLE). Among them, cerebral arterial dissection is a rare vascular complication, in which an intimal tear of the blood vessel leads to an intramural hematoma. Cerebral arterial dissection leads to arterial stenosis, thrombosis, and aneurysm, resulting in cerebral infarction or subarachnoid hemorrhage (SAH). Herein, we report a case of posterior cerebral artery (PCA) dissection in SLE that presented as unilateral thalamic infarction followed by SAH and intraventricular hemorrhage (IVH). Case PresentationA 16-year-old boy hospitalized with prolonged fever, hair loss, and skin eruption was newly diagnosed with SLE based on the 2019 EULAR/ACR SLE classification criteria. He suddenly complained of headache, diplopia, and impairment of lateral gaze during hospitalization. Brain magnetic resonance imaging revealed left thalamic infarction, although cerebral vessel inflammation or thrombosis was not observed. Antiphospholipid antibodies such as lupus anticoagulant, anti-cardiolipin antibody, and anti-β2-glycoprotein antibody were not detected. His symptoms improved with high-dose steroid, low-dose aspirin, and mannitol therapy. Five days later, he experienced severe headache and generalized tonic-clonic seizures. Brain computed tomography revealed SAH and IVH with hydrocephalus. Even though emergent external ventricular drainage was performed, the ventricle size did not decrease. Transfemoral cerebral angiography revealed a ruptured dissecting PCA pseudoaneurysm, and immediate coil embolization was successfully performed. The patient fully recovered without any neurologic sequelae, although he underwent ventriculoperitoneal shunting for hydrocephalus following SAH. ConclusionsTo the best of our knowledge, this is the first reported case of PCA dissection in a patient with childhood-onset SLE. Moreover, the subsequent progression from cerebral infarction to SAH caused by PCA dissection makes this case unique. In SLE patients presenting with cerebral infarction and hemorrhage, cerebral arterial dissection and pseudoaneurysm should be considered to achieve favorable outcomes.