[Treatment of tandem occlusions of the common and internal carotid arteries]. / Behandlung von Tandemstenosen der A. carotis communis und A. carotis interna.

BACKGROUND: Proximal carotid tandem lesions are defined as multilevel lesions with significant (> 50%) atherosclerotic disease involving the internal carotid artery (ICA) in combination with the proximal ipsilateral common carotid artery (CCA) or innominate artery (IA). It is a relatively rare disease with an incidence of less than 5% in all patients with carotid stenosis at the level of the bifurcation. METHODS: These patients are at high surgical risk and were, therefore, excluded from current randomized controlled trials. Although the effectiveness of carotid endarterectomy (CEA) and carotid stenting (CAS) in stroke prevention for patients is established, the optimal treatment approach for the subgroup of patients with a proximal tandem lesion is still controversial. Treatment of this condition is not well understood because it is difficult to determine the risk of each individual lesion becoming symptomatic. Therefore, concurrent treatment of severe (> 70% stenosis) proximal lesions is recommended when treating severe stenosis at the carotid bifurcation. CONCLUSION: This disease can lead to embolic ischemic strokes or hemodynamic compromise. It is not possible to determine diagnostically which lesion led to the clinical symptoms, which is why both lesions should be corrected.

Local carotid stiffness, hemodynamic forces and blood viscosity in patients with cerebral lacunar infarctions.

OBJECTIVE: The carotid stiffness is an important factor in the pathogenesis of cerebrovascular small vessel disease. Our study aimed to evaluate the relation of the local arterial stiffness of the common carotid artery (CCA) to the hemodynamic forces and blood viscosity in patients with cerebral lacunar infarctions (LI). METHODS: Twenty-two patients with chronic LI and 15 age-matched controls were examined. An ultrasound examination of the CCA intima-media thickness (IMT), the parameters of local CCA stiffness: distensibility (DC) and compliance coefficients (CC), α and ß stiffness indices and pulse wave velocity (PWV) was performed. The local hemodynamic forces were calculated: circumferential wall tension (CWT) and wall shear stress (WSS). Whole blood viscosity (WBV) and shear stresses at shear rates of 0.277 s- 1 to 94.5 s- 1 were measured in patients and controls. RESULTS: Higher values of IMT, a significant decrease of DC and CC and an increase of α and ß stiffness indices and PWV in the LI patients compared to the controls were obtained. A parallel significant increase in CWT and a decrease in WSS was found. An increase in WBV and a significant increase in shear stresses were detected. In the LI patients, the increased stiffness indices were associated with an increase in age, cholesterol and WBV at higher shear rates in the left CCA. In the controls, the IMT and stiffness indices correlated significantly with the hemodynamic factors and WBV in both CCAs, while the stiffness indices correlated with the hemodynamic forces in the left CCA. CONCLUSION: The results of the present study demonstrate different associations of the local carotid stiffness indices with the hemodynamic forces and WBV in patients with LI and controls.

Common carotid artery intima media thickness (CIMT) in patients with prediabetes and newly diagnosed type 2 diabetes mellitus.

AIM: To evaluate the relationship between common carotid artery intima media thickness (CIMT) in patients with prediabetes and new-onset diabetes mellitus without proven cardiovascular disease and some classic cardio-metabolic risk factors. PATIENTS AND METHODS: The study included 461 obese patients with an average age of 53.2 ± 10.7 years, divided into three groups - group 1 without carbohydrate disturbances (n = 182), group 2 with prediabetes (n = 193) and group 3 with newly diagnosed diabetes mellitus (n = 86). RESULTS: The patients with new-onset diabetes had significantly higher mean CIMT values compared to those with prediabetes or without carbohydrate disturbances and a higher frequency of abnormal IMT values. CIMT correlated significantly with age, systolic BP, diastolic BP and fasting blood glucose and showed a high predictive value for the presence of diabetic neuropathy and sudomotor dysfunction. Patients with abnormal CIMT values had a higher incidence of arterial hypertension, dyslipidemia, metabolic syndrome, peripheral neuropathy, and sudomotor dysfunction. Patients who developed type 2 diabetes during follow-up had a significantly higher initial mean CIMT, which showed the highest predictive value for the risk of new-onset diabetes, with CIMT≥0.7 mm having 53 % sensitivity and 83 % specificity for the risk of progression to diabetes mellitus. CONCLUSION: Patients with new-onset diabetes mellitus had significantly greater intima media thickness of the common carotid artery and a greater frequency of abnormal CIMT values compared to those with normoglycemia and prediabetes. CIMT has a high predictive value for the presence of diabetic neuropathy, sudomotor dysfunction and the risk of new onset diabetes.

Vasa vasorum interna in the carotid wall of active forms of Takayasu arteritis evidenced by ultrasound localization microscopy.

Introduction: Takayasu arteritis (TA) is associated with microvascularization of the wall of large arteries and is related to inflammation. Ultrasound localization microscopy (ULM), combining ultrafast ultrasound imaging with microbubble (MB) injection, can track the path of MBs within the arterial wall and thus provide imaging of the vasa vasorum. From the analysis of MB tracks in the common carotid arteries of patients with active TA, we report the presence of microvessels in connection with the carotid lumen (i.e., vasa vasorum interna [VVI]). Methods: ULM maps were obtained on five patients with active disease in the observational single-center series of the TAK-UF study. MB tracks connected to the carotid lumen were automatically identified, allowing the reconstruction of VVI. Results: MB tracking allows us to observe a microvascular network on the inner part of the wall, with some vessels in communication with the carotid lumen. This type of vessel was identified in all patients with active TA (n = 5) with a median of 2.2 [1.1-3.0] vessels per acquisition (2D longitudinal view of 3 cm of the common carotid artery). The blood flow within these vessels is mainly centrifugal; that is, toward the adventitia (88% [54-100] of MB tracks with flow directed to the outer part of the wall). Conclusion: VVI are present in humans in the case of active TA and emphasize the involvement of the intima in the pathological process. ClinicalTrials.gov Identifier: NCT03956394.

Intima-Media Thickness in the Carotid Bifurcation is Related to Silent Brain Infarction: A Cross-Sectional Study.

AIMS: Carotid intima-media thickness (IMT) measurement is used to assess subclinical atherosclerosis. We aimed to examine the association between the maximum IMT by location and the occurrence of silent brain infarction (SBI). METHODS: Overall, 280 Japanese individuals (92 females, 52.6±5 years old) underwent a medical check-up at our hospital in Tokyo in 2015. Carotid IMT was measured at each site on ultrasound images (common carotid artery [CCA], internal carotid artery, or bifurcation). The risk factors for arterial dysfunction were evaluated. SBI was assessed using magnetic resonance imaging (MRI). The cross-sectional relationship between carotid maximum IMT and SBI was evaluated. RESULTS: Of the 280 individuals, 18 (6.4%) were diagnosed with SBI on MRI. The mean age of the SBI(-) and SBI(+) groups was 51.9±10.6 and 63.6±18.6 years, respectively. The correlation coefficients between the carotid maximum IMT at each location were very weak (correlation coefficient range: 0.180-0.253). The percentage of participants with SBI increased significantly with increasing maximum CCA and bIMT values. After adjusting for confounders, SBI was found to be significantly associated with the maximum bIMT (per 0.1-mm increase) (adjusted odds ratio [aOR], 1.10; 95% confidence interval [CI]: 1.03-1.17). When bIMT was categorized according to three groups (＜1.0 mm, 1.0-＜2.0 mm, and ≥ 2.0 mm), a significant SBI risk was also observed with an increase by each category of bIMT (aOR: 3.96, 95% CI: 1.63-9.52, P=0.002). CONCLUSION: The maximum bIMT was found to be the main determinant of SBI. A significant SBI risk was associated with an increase in each category of the maximum bIMT. Therefore, the maximum bIMT might be a useful predictor of future stroke in Japanese stroke-free medical check-up participants.

Association of cumulative low-density lipoprotein cholesterol exposure with vascular function.

BACKGROUND: The relationship between cumulative low-density lipoprotein cholesterol (LDL-C) exposure and progression of atherosclerosis remains uncertain. OBJECTIVE: The aim of this study was to determine the relationship between cumulative LDL-C level and flow-mediated vasodilation (FMD), nitroglycerine-induced vasodilation (NID) and the presence of plaque in the common carotid artery (CCA). METHODS: This was a cross-sectional study. We measured FMD in 8208 subjects, NID in 1822 subjects, and CCA plaque in 591 subjects who were not taking lipid-lowering drugs. The subjects were divided into four groups based on cumulative LDL-C exposure: <4000 mg·year/dL, 4000-4999 mg·year/dL, 5000-5999 mg·year/dL, and ≥6000 mg·year/dL. RESULTS: The odds ratio of the lower quartile of FMD in the cholesterol-year-score <4000 mg·year/dL group was significantly higher than the odds ratios in the other groups. The odds ratio of the lower quartile of NID in the <4000 mg·year/dL group was significantly higher than the odds ratios in the 5000-5999 mg·year/dL and ≥6000 mg·year/dL groups. The odds ratio of the prevalence of CCA plaque in the <4000 mg·year/dL group was significantly higher than that in the ≥6000 mg·year/dL group. CONCLUSIONS: Endothelial dysfunction occurred from cumulative LDL-C exposure of 4000 mg·year/dL, vascular smooth muscle dysfunction occurred from cumulative LDL-C exposure of 5000 mg·year/dL, and prevalence of CCA plaque occurred from cumulative LDL-C exposure of 6000 mg·year/dL. CLINICAL TRIAL REGISTRY INFORMATION: http://www.umin.ac.jp (UMIN000012950, UMIN000012951, and UMIN000012952, UMIN000003409).

Efficacy and safety of a treatment in patients with locoregionally advanced nasopharyngeal carcinoma (LANC) involving carotid artery invasion.

PURPOSE: Locally advanced nasopharyngeal carcinoma (LANC) often invades the parapharyngeal space and internal carotid artery. Are patients with LANC invading carotid artery are at risk of massive neck hemorrhage after radiotherapy? METHODS: This retrospective study included 130 LANC patients with carotid artery invasion admitted to our hospital between January 2012 and September 2019. All patients were treated with induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) ± epidermal growth factor receptor (EGFR) inhibitor. Univariate and multivariate analysis of risk factors were conducted for the prognosis and the occurrence of massive neck hemorrhage of LANC patients with carotid artery invasion. OUTCOMES: The 5-year progression-free survival (PFS), distant metastasis-free survival (DMFS), local nodal recurrence-free survival (LNRFS), local recurrence-free survival (LRFS), nodal recurrence-free survival (NRFS) and overall survival (OS) of the 130 patients were 75.2%, 76.8%, 90.0%, 93.9%, 95.8% and 87.2%, respectively. The incidence of fatal bleeding after radiotherapy was 2.3% (3/130). The primary site of the three cases were all the pharyngeal recess, with more than 270° carotid artery invasion, suffering nasopharyngeal necrosis after radiotherapy (2 of which were diabetics and 1 received re-radiation after recurrence). Univariate analysis showed that clinical stage was negatively correlated with DMFS and PFS (P < 0.05). The induction chemotherapy TP regimen, platinum-based concurrent chemotherapy and EGFR inhibitors (Nituzumab/Cetuximab) significantly improved PFS and DMFS (P < 0.05). Patients with hemoglobin levels > 110 g/L had significantly inferior PFS, DMFS and OS than those with hemoglobin levels ≤ 110 g/L (P < 0.05). Multivariate analysis showed that the EGFR inhibitor was an independent risk factor for PFS and DMFS, while the lowest hemoglobin level was an independent risk factor for OS. CONCLUSIONS: In LANC patients whose carotid artery invasion was < 270°, induction chemotherapy (IC) followed by helical tomotherapy (HT) and concurrent chemoradiotherapy (CCRT) with EGFR (epidermal growth factor receptor) inhibitor had mild and tolerable side effects, better PFS and DMFS, with no massive hemorrhage. In patients whose primary tumor was pharyngeal recess with carotid artery invasion ≥ 270°, poorly controlled diabetes or re-radiotherapy led to a higher risk of massive hemorrhage after radiotherapy.

Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice.

BACKGROUND: Vascular cognitive impairment (VCI) is the second-leading cause of dementia worldwide, which is caused by cerebrovascular diseases or relevant risk factors. However, there are no appropriate animal models, which can be used to study changes of neuropathology in the human VCI. To better understand the development of VCI, we modified three mouse models of chronical vascular diseases, and further compared the advantage and disadvantage of these models. We hope to establish a more suitable mouse model mimicking VCI in human beings. METHODS: Adult male C57/BL6 mice (n=98) were used and animals underwent transient bilateral common carotid arteries occlusion (tBCCAO), or bilateral common carotid artery stenosis (BCAS), or right unilateral common carotid artery occlusion, respectively. Haemodynamic changes of surface cerebral blood flow (CBF) were examined up to 4 weeks. Spatial cognitive impairment was evaluated to determine the consequence of chronic cerebral ischaemia. RESULTS: These mouse models showed different extents of CBF reduction and spatial reference memory impairment from 1 week up to 4 weeks postoperation compared with the control group (p<0.05). We found that (1) bilaterally ligation of common carotid artery caused decrease of 90% CBF in C57/BL6 mice (p<0.05) and caused acute instead of prolonged impairment of spatial reference memory (p<0.05); (2) unilateral ligation of common carotid artery did not cause severe ipsilateral ischaemia as seen in the tBCCAO mice and caused minor but significant spatial reference memory disturbance (p<0.05); and (3) 20% decrease in the bilateral CBF did not cause spatial reference memory impairment 4 weeks postoperation (p>0.05), while 30% decrease in bilateral or unilateral CBF led to significant memory disturbance in mice (p<0.05). CONCLUSION: We demonstrated that BCAS using 0.16/0.18 mm microcoils is an alternative VCI mouse model when studying the mechanism and developing therapy of VCI.

Plasma 24-hydroxycholesterol is associated with narrower common carotid artery and greater flow velocities in relapsing multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) studies suggest greater cardiovascular disease burden and disturbances in the cholesterol pathways. The potential impact of oxidized cholesterol molecules on MS is emerging. OBJECTIVE: To determine the relationship between multiple oxysterol molecules and atherosclerosis burden in MS patients. MATERIALS AND METHODS: A total of 99 MS patients (61 relapsing-remitting MS(RRMS) and 38 progressive MS (PMS)) patients and 38 healthy controls (HCs) underwent magnetic resonance angiography (MRA) and the cross-sectional area (CSA) of the common carotid artery (CCA) was determined at three different levels before the bifurcation (C7, C6 and C5). Additionally, an echo-color Doppler ultrasound was performed and measures of blood flow velocities were derived. Blood samples acquired at the time of the imaging examinations were analyzed and 24-, 25-, 27-hydroxycholesterol (24HC, 25HC, 27HC) and 7-ketocholesterol (7KC) were quantified in ng/mL RESULTS: In the MS patients, higher levels of 24HC were significantly associated with smaller CCA CSA measured at all three cervical levels (r=-0.201, p = 0.046; r=-0.228, p = 0.023, and r=-0.215, p = 0.032, for C7, C6 and C5, respectively). These associations were driven by the RRMS group only (r=-0.407, p = 0.002 for C7; r=-0.414, p = 0.002, for C6; and r=-0.368, p = 0.006 for C5). No associations were seen in the HCs. Despite adjusting for the significant age effect (B = 0.445, p = 0.004), higher 24HC levels were independently associated with smaller CCA CSA (B=-0.20, p = 0.045). 24HC was additionally associated with greater time-averaged and peak diastolic CCA velocities. RRMS patients treated with potent anti-inflammatory therapies had lower oxysterol levels (p = 0.019). CONCLUSION: Greater 24HC levels are associated with smaller CSA CCA and greater flow velocities in RRMS patients.

Bilateral carotid artery geometry using magnetic resonance angiography: a 10-year longitudinal single center study.

Aging and atherosclerotic progression can lead to geometric changes in the carotid arteries. We conducted a longitudinal study to investigate geometric changes in the bilateral carotid arteries. We conducted a retrospective study of 177 subjects who underwent carotid contrast-enhanced magnetic resonance angiography (MRA) at our clinic at baseline and 10 years after the procedure. Semi-automated methods were used to segment the bilateral carotid arteries to obtain carotid artery geometric measurements. The mean age for the total population after 10 years was 70.7 ± 10.6 years (male, 40.1%). The mean time interval between baseline and after 10 years for all subjects was 130.2 ± 8.1 months. The bilateral bifurcation angle, the diameters for both common carotid arteries (CCAs), and areas of both CCAs significantly increased (p < 0.001) over a 10-year period. The maximum diameter and internal carotid artery area did not significantly change. The bifurcation angle of the right carotid artery was significantly increased compared to the left carotid artery. However, the diameter and area of the CCA of the left carotid artery was significantly increased compared to the right carotid artery. The bifurcation angle, diameter and area of both CCAs significantly increased over a decade. The change in the bifurcation angle over a 10-year period was predominant in the right carotid artery and the change of the area and diameter of the CCA was dominant in the left carotid artery.

Immature Vascular Smooth Muscle Cells in Healthy Murine Arteries and Atherosclerotic Plaques: Localization and Activity.

The local development of atherosclerotic lesions may, at least partly, be associated with the specific cellular composition of atherosclerosis-prone regions. Previously, it was demonstrated that a small population of immature vascular smooth muscle cells (VSMCs) expressing both CD146 and neuron-glial antigen 2 is postnatally sustained in atherosclerosis-prone sites. We supposed that these cells may be involved in atherogenesis and can continuously respond to angiotensin II, which is an atherogenic factor. Using immunohistochemistry, flow cytometry, wound migration assay xCELLigence system, and calcium imaging, we studied the functional activities of immature VSMCs in vitro and in vivo. According to our data, these cells do not express nestin, CD105, and the leptin receptor. They are localized in atherosclerosis-prone regions, and their number increases with age, from 5.7% to 23%. Immature VSMCs do not migrate to low shear stress areas and atherosclerotic lesions. They also do not have any unique response to angiotensin II. Thus, despite the localization of immature VSMCs and the presence of the link between their number and age, our study did not support the hypothesis that immature VSMCs are directly involved in the formation of atherosclerotic lesions. Additional lineage tracing studies can clarify the fate of these cells during atherogenesis.

Challenges of Surgical Resection of Carotid Body Tumors - Multiple Feeding Arteries and Preoperative Embolization.

BACKGROUND: Carotid body tumor is a hypervascular tumor with multiple feeding arteries and unique orientation at the carotid bifurcation. Although resection is a radical therapy for this tumor, complete resection is challenging. MATERIALS AND METHODS: Articles reporting carotid body tumor treatment and surgical resection were reviewed including case-control series and review articles. RESULTS: Selected reports were reviewed and discussed focusing on choice of treatment, surgical difficulties and preoperative embolization of feeding arteries. CONCLUSION: Multiple feeding arteries and adhesion of the tumor to the carotid arterial wall are causes of difficulties in carotid body tumor resection. The effectiveness of preoperative embolization remains controversial due to the varied situations in performing surgical resection among the institutions. However, perfect embolization and resection immediately after embolization reduce blood loss and operative time of surgery for carotid body tumor.

Reference luminal diameters of the carotid arteries among healthy Nigerian adults.

BACKGROUND: The carotid arteries serve as major blood supply to the head and neck region of the body. Understanding their structure and function in the pathogenesis of stroke and in interventional neuroradiology due to luminal stenosis, atherosclerosis and wall stiffness is paramount. Doppler ultrasound scan plays key role in the early diagnosis of the pathologies of the arteries as it is an affordable, accessible, reliable and non-invasive clinical tool. Knowing normal average diameter of the carotid arteries among healthy individuals is important in making correct clinical diagnosis in any population. The aim of the study was to determine mean diameters of the carotid arteries among healthy adult Nigerians for reference. MATERIALS AND METHODS: This was a prospective study involving 104 healthy Nigerians within the ages of 18 and 65 years who had their carotid arteries scanned on both sides and each diameter was measured. A 95% confidence level was used; a p-value of < 0.05 was significant. RESULTS: Of the studied population, 62 were males and 42 were females, and the average age of the subjects was 28.32 ± 9.09 years. From this study, the average luminal diameter of the common carotid artery = 0.61 ± 0.08 cm, internal carotid artery = 0.60 ± 0.08 cm and external carotid artery = 0.49 ± 0.10 cm. The results showed that although, there are differences in measurements between the two sexes (males slightly higher than females in common carotid artery) and between right and left sides (with right side slightly higher), they are not statistically significant. CONCLUSIONS: This sonographic study on healthy Nigerian adults has given us normal reference values of the luminal diameters of the carotid arteries among Nigerians, which clinicians can make reference to, when assessing carotid artery diameters of patients in Nigeria.

Vascular Response Toward an Absorbable Sirolimus-eluting Polymeric Scaffold for Vascular Application in a Model of Normal Porcine Carotid Arteries.

BACKGROUND: Fully absorbable polymeric scaffolds, as a potential alternative to permanent metallic stents, are entering the clinical field. The aim of this study is to assess the in vivo biocompatibility of a novel Sirolimus-eluting (SIR) absorbable scaffold based on poly(L-lactide) (PLLA) and poly(4-hydroxybutyrate) (P4HB) for interventional application. METHODS: Absorbable PLLA/P4HB scaffolds either loaded with SIR coating or unloaded scaffolds were implanted interventionally into common carotid arteries of 14 female. Bare metal stents (BMS) served as control. Peroral dual anti-platelet therapy was administered throughout the study. Stented common carotid arteries segments were explanted after 4 weeks, and assessed histomorphometrically. RESULTS: The absorbable scaffolds showed a decreased residual lumen area and higher stenosis after 4 weeks (PLLA/P4HB: 6.56 ± 0.41 mm² and 37.56 ± 4.67%; SIR-PLLA/P4HB: 6.90 ± 0.58 mm² and 35.60 ± 3.15%) as compared to BMS (15.29 ± 1.86 mm² and 7.65 ± 2.27%). Incorporation of SIR reduced the significantly higher inflammation of unloaded scaffolds however not to a level compared to bare metal stent (PLLA/P4HB: 1.20 ± 0.19; SIR-PLLA/P4HB: 0.96 ± 0.24; BMS: 0.54 ± 0.12). In contrast, the BMS showed a slightly elevated vascular injury score (0.74 ± 0.15), as compared to the PLLA/P4HB (0.54 ± 0.20) and the SIR-PLLA/P4HB (0.48 ± 0.15) groups. CONCLUSION: In this preclinical model, the new absorbable polymeric (SIR-) scaffolds showed similar technical feasability and safety for vascular application as the permanent metal stents. The higher inflammatory propensity of the polymeric scaffolds was slightly reduced by SIR-coating. A smaller strut thickness of the polymeric scaffolds might have been a positive effect on tissue ingrowth between the struts and needs to be addressed in future work on the stent design.

The Wandering Nerve: Positional Variations of the Cervical Vagus Nerve and Neurosurgical Implications.

BACKGROUND: The vagus ("wandering") nerve is the longest cranial nerve with the largest territory of innervation in the human body. Injury during various operative procedures involving the anterior or lateral neck may lead to serious complications. Per "textbook" descriptions, the cervical vagus nerve (CVN) commonly locates within the carotid sheath, in between the common carotid artery (CCA) and internal jugular vein (IJV). However, anatomic variations in its positioning may occur more often than expected and intraoperative identification may anticipate potential surgical pitfalls. METHODS: A literature review was conducted per PRISMA guidelines for all studies describing positional variations of the CVN within the carotid sheath. A rare and potentially dangerous variation, occurring in only 0.7% of all reported cases, is illustrated with a cadaveric case. RESULTS: Overall, 10 anatomic CVN variations have been described across 971 specimens. The non-textbook variations (26.5%) consist of: lateral (4.7%), anterolateral (8.7%), posteromedial (0.2%), posterior (5.8%), anterior (3.1%), medial (0.7%), and anteromedial (0.4%) to the CCA, as well as posterolateral (0.3%) and posterior (2.6%) to IJV. The "textbook" anatomic location is posterolateral to CCA (73.5%). Moreover, an increase in variability is reported on the left side (17.1%) compared with the right (11.3%). Our cadaveric dissection revealed a right-sided CVN directly medial to the CCA. CONCLUSIONS: Positional variations of the CVN occur in over 26% of patients and may add difficulty to an array of surgical procedures. Knowledge of these variations and their prevalence may aid the surgeon in conducting a more precise dissection possibly preventing significant potential adverse sequelae.

Exploring the mechanism of Danggui Buxue Decoction in regulating atherosclerotic disease network based on integrated pharmacological methods.

OBJECTIVE: To explore the mechanism of Danggui Buxue Decoction (DGBXD) in regulating Atherosclerosis (AS) network based on integrated pharmacological methods. METHODS: The active ingredients and targets of DGBXD are obtained from TCMSP database and ETCM. AS-related targets were collected from the Genecards and OMIM databases. The drug-disease protein interaction (PPI) networks were constructed by Cytoscape. Meanwhile, it was used to screen out densely interacting regions, namely clusters. Finally, Gene Ontology (GO) annotations are performed on the targets and genes in the cluster to obtain biological processes, and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations are performed on the targets of the PPI network to obtain signaling pathways. RESULTS: A total of 212 known targets, 265 potential targets and 229 AS genes were obtained. The 'DGBXD known-AS PPI network' and 'DGBXD-AS PPI Network' were constructed and analyzed. DGBXD can regulate inflammation, platelet activation, endothelial cell apoptosis, oxidative stress, lipid metabolism, vascular smooth muscle proliferation, angiogenesis, TNF, HIF-1, FoxO signaling pathway, etc. The experimental data showed that compared with the model group, the expressions of ICAM-1, VCAM-1, and interleukin (IL)-1ß protein and mRNA in the DGBXD group decreased (P<0.05). However, plasma IL-1ß, TNF-α, and MCP-1 in the DGBXD group were not significantly different from the model group (P>0.05). CONCLUSION: The mechanism of DGBXD in the treatment of AS may be related to the improvement of extracellular matrix (ECM) deposition in the blood vessel wall and the anti-vascular local inflammatory response, which may provide a reference for the study of the mechanism of DGBXD.

Early Atherosclerotic Inflammatory Pathways in Children with Obstructive Sleep Apnea.

OBJECTIVE: To evaluate structural and functional carotid changes and inflammatory profiles in children with obstructive sleep apnea (OSA) and healthy controls. STUDY DESIGN: Patients with OSA and matched controls (ages 5-13 years) were recruited. Proinflammatory cytokines and acute phase reactants were measured at 6:00 p.m. Common carotid artery measures were determined using ultrasound. Confirmatory factor analysis was used to determine subgroups of cytokines and their effects on carotid measures. RESULTS: Ninety-six patients participated (53 healthy controls, 43 patients with OSA). OSA was associated with increased proinflammatory cytokines (cluster of differentiation-40 ligand [CD40-L], interleukin [IL]-6, and IL-8) and high sensitivity C-reactive protein (P < .05 for all). One cytokine subgroup (IL-6 and IL-8) was negatively associated with markers of carotid function, indicating reduced arterial distensibility and increased stiffness (P < .05 for 3 ultrasound measures); and tumor necrosis factor-α had an opposing effect on carotid function compared with this cytokine subgroup (P < .05 for 2 ultrasound measures). Linear regression demonstrated significant associations between and tumor necrosis factor- α and 2 measures of carotid function (P < .05 for each). Children with OSA did not have functional or structural carotid changes compared with controls. CONCLUSION: OSA was not directly associated with structural and functional carotid changes but was associated with upregulation of key proinflammatory cytokines (sCD40-L, IL-6, and IL-8). Together, IL-6 and IL-8 were associated with changes in carotid function. Longitudinal studies are needed to demonstrate that the inflammatory milieu observed in our population is a precursor of atherosclerosis in children.

Irradiation Accelerates Plaque Formation and Cellular Senescence in Flow-Altered Carotid Arteries of Apolipoprotein E Knock-Out Mice.

Background Chronic inflammation through cellular senescence, known as the senescence-associated secretory phenotype, is a mechanism of various organ diseases, including atherosclerosis. Particularly, ionizing radiation (IR) contributes to cellular senescence by causing DNA damage. Although previous clinical studies have demonstrated that radiotherapy causes atherosclerosis as a long-term side effect, the detailed mechanism is unclear. This study was conducted to investigate the relationship between radiation-induced atherosclerosis and senescence-associated secretory phenotype in murine carotid arteries. Methods and Results Partial ligation of the left carotid artery branches in 9-week-old male apolipoprotein E-deficient mice was performed to induce atherosclerosis. The mice received total body irradiation at a dose of 6 Gy using gamma rays at 2 weeks post operation. We compared the samples collected 4 weeks after IR with unirradiated control samples. The IR and control groups presented pathologically progressive lesions in 90.9% and 72.3% of mice, respectively. Plaque volume, macrophage accumulation, and phenotype switching of vascular smooth muscle cells were advanced in the IR group. Irradiated samples showed increased persistent DNA damage response (53BP1 [p53 binding protein 1]), upregulated cyclin-dependent kinase inhibitors (p16INK4a and p21), and elevated inflammatory chemokines expression (monocyte chemotactic protein-1, keratinocyte-derived chemokine, and macrophage inflammatory protein 2). Conclusions IR promoted plaque growth in murine carotid arteries. Our findings support the possibility that senescence-associated secretory phenotype aggravates atherogenesis in irradiated artery. This mice model might contribute to mechanism elucidation of radiation-induced atherosclerosis.

Selective intra-carotid blood cooling in acute ischemic stroke: A safety and feasibility study in an ovine stroke model.

Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model.Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep. In the hypothermia group (n = 10), selective TH was initiated 20 minutes before recanalization, and was maintained for another 3 h. In the normothermia control group (n = 10), a standard 8 French catheter was used instead. Primary endpoints were intranasal cooling performance (feasibility) plus vessel patency assessed by digital subtraction angiography and carotid artery wall integrity (histopathology, both safety). Secondary endpoints were neurological outcome and infarct volumes.Computed tomography perfusion demonstrated MCA territory hypoperfusion during MCAO in both groups. Intranasal temperature decreased by 1.1 °C/3.1 °C after 10/60 minutes in the TH group and 0.3 °C/0.4 °C in the normothermia group (p < 0.001). Carotid artery and branching vessel patency as well as carotid wall integrity was indifferent between groups. Infarct volumes (p = 0.74) and neurological outcome (p = 0.82) were similar in both groups.Selective TH was feasible and safe. However, a larger number of subjects might be required to demonstrate efficacy.

Corilagin ameliorates atherosclerosis by regulating MMP-1, -2, and -9 expression in vitro and in vivo.

Corilagin is a polyphenol has been identified anti-inflammatory properties. However, the anti-atherosclerotic effects of corilagin are not well understood. Here, we evaluated the anti-atherosclerotic effects and the underlying mechanisms of corilagin. We also verified whether corilagin can reverse atherosclerosis by regulating matrix metalloproteinase (MMP)-1, -2, and -9 in vitro and in vivo. An atherosclerosis model was established by feeding minipigs a high-fat diet combined with balloon injury, and the effects of different concentrations of corilagin on common carotid artery atherosclerosis in minipigs were monitored. Murine RAW264.7 macrophages were cultured and induced with oxidized low-density lipoprotein; fluorescence microscopy revealed the nuclear translocation of NF-κB. Furthermore, MMP-1, -2, and -9 expression in common carotid artery plaques and cellular models was detected by immunohistochemistry, western blotting, and RT-PCR. The pathological results suggested that the vascular intima of the model control group was significantly thickened, a large amount of collagen fibers was deposited, endothelial cells were damaged and detached, and plaque and foam cell formation occurred to varying degrees on the arterial wall, with lipid deposition. Corilagin treatment significantly reduced the degree of injury in the common carotid artery and decreased the number of lipid plaques and foam cells. Additionally, corilagin downregulated MMP-1, -2, and -9 expression in the common carotid artery plaques and cellular model. Moreover, corilagin significantly inhibited NF-κB nuclear translocation in vitro. Overall, corilagin exerted substantial therapeutic effects on experimental atherosclerotic minipigs via the downregulation of MMP-1, -2, and -9 expression.