Carotid Artery Research Articles

Genetic and epigenetic factors affecting carotid intima-media thickness in monozygotic twins

Background and aimsThe intima-media thickness (IMT) of the carotid artery, an indicator of subclinical atherosclerosis, varies in close association with various factors such as diabetes and immune response. The extent of changes in IMT varies among individuals owing to both genetic and epigenetic factors. In this study, we aimed to identify single nucleotide polymorphisms (SNPs) and DNA methylation patterns that affect carotid IMT in monozygotic (MZ) twins. MethodsWe measured the maximum IMT (IMT-Cmax) and the mean IMT in the common carotid artery wall using ultrasonography in 107 pairs of MZ twins recruited from the Osaka University Twin Registry. The genotyping of SNPs and the measurement of methylation levels were performed using a beads array, and the expression of each gene was determined by RNA sequencing. Linear regression analysis was performed on each of the two groups: one group consisted of twins randomly selected from each pair, and the other group consisted of co-twins. ResultsWe identified a CpG site (cg02432467) on HS3ST6 as a significant epigenetic factor in both IMT-Cmax and mean IMT analyses. The methylation level at another site (cg07927379) was negatively correlated with LINC01006 expression and IMT-Cmax. Furthermore, there were significant differences in AP2A2 expression and mean IMT among individuals with each genotype of the rs10902263 polymorphism. ConclusionsWe identified genetic and epigenetic factors associated with carotid IMT that may be useful for individualized assessments.

INTRACRANIAL ANEURYSMS IN CHILDREN - A NEW PERSPECTIVE

Introduction Intracranial aneurysms in children are very rare pathologic entities. (1200 cases presented in literature from 1939-2011). Material and Methods The authors present 51 cases of children (aged: 0-16) operated between January 1999 and December 2023 - 24 years in three neurosurgical centers: “Bagdasar Arseni” Emergency University Hospital (Bucharest), Sanador Clinical Hospital (Bucharest) and Timis County Emergency Hospital (Timisoara). We collected data from many children’s intracranial aneurysms cases because “Bagdasar-Arseni” Emergency University Hospital has the most important pediatric neurosurgical unit in the country. Regarding our series, pediatric aneurysms represent 6.14% (51 cases) of all operated intracranial aneurysms (765 cases). The mean age of the patients was 14.3 years. There were 29 boys (58.7%) and 22 girls (41.2%). The clinical features are dominated by headache (48 cases - 95.7%), neck stiffness (45 cases - 91.4%), vomiting (44 cases - 89.3%), focal neurological deficit (24 cases - 44.6%), an altered level of consciousness (17 cases - 36.1%), seizures (24 cases - 44.6%, fever (20 cases - 34%). The majority of patients were Hunt & Hess Il at admittance (27 cases, 53%). All neuroimagistic investigations were done in the first 48 hours (CT, DSA, MRI). Locations: anterior communicating artery aneurysms (20 cases, 36.1%), followed by middle cerebral artery aneurysms (15 cases, 25.5%) and internal carotid artery bifurcation aneurysms (9 cases, 19.1%) and so on. Many aneurysms were large and giant (18 cases - 31.9%). Microsurgery approach was performed in 48 cases (99.7%) and 3 case (4.4%) were endovascular approached. This represents a new vision because the actual endovascular way is extremely efficient and performant in occluding pediatric intracranial aneurysms. The Glasgow Outcome Scale (GOS) at six months postop. showed GR in 40 cases (78.5%), MD in 9 cases (17.2%), SD in 1 patient (2.1%) and (preoperative) death in 1 patient (2.1%). Conclusions Intracranial aneurysms in children are a very rare pathologic entity. Early microsurgical or endovascular approach is mandatory and has excellent results (good recovery).

Prolonged intracranial catheter dwell time exacerbates penumbral stress and worsens stroke thrombectomy outcomes

BackgroundThe duration of mechanical thrombectomy (MT) is a negative predictor of outcomes in acute ischemic stroke (AIS), yet the precise mechanisms are unclear. We investigated whether the placement of large-bore...

SURGICAL RESECTION OF A COMPLEX TUBERCULUM SELLAE MENINGIOMA ENCASING MAJOR ARTERIES

Introduction Though constituting only a minor proportion (1%) of sellar masses, suprasellar meningiomas pose a significant diagnostic challenge within the region of sellar and suprasellar tumors. Pituitary adenomas, at nearly 90% prevalence, dominate this anatomical region. Distinguishing these two entities is paramount, as both clinical presentation and, to some extent, biochemical profiles exhibit notable overlap. Accurate preoperative differentiation is critical due to the contrasting behaviors of these tumors. Meningiomas, with their robust vascularity supplied by dural and osseous arteries, present a heightened risk of intraoperative hemorrhage. Clinical Case A 53-year-old woman presented with a two-month history of worsening headaches and gradual vision loss. Neurological examination revealed only visual acuity decline. Her hormone profile showed elevated prolactin but lacked clinical features of prolactin excess, suggesting a possible prolactin-secreting pituitary macroadenoma. A contrast-enhanced MRI confirmed a significant sellar and suprasellar mass with homogeneous enhancement, extending to the right paramedian region and encasing the right internal carotid artery (ICA) at its critical segment involving the cavernous and supraclinoid portions. Furthermore, the right middle meningeal artery (M1) and anterior cerebral artery (A1) originated from this same location, highlighting the high surgical risk. Surgical resection was deemed necessary. The patient underwent a right pterional craniotomy, revealing a grayish, extradural soft mass lesion encasing the ICA bifurcation. Careful microsurgical dissection with basal devascularization was performed, followed by near-complete tumor removal using an ultrasonic aspirator to minimize damage to the encased arteries. Postoperative follow-up CT scan confirmed successful near-total tumor ablation. Conclusion This case underscores the critical role of meticulous preoperative diagnosis in managing complex sellar tumors. While pituitary adenomas dominate this region, suprasellar meningiomas, despite their rarity, demand a high index of suspicion. Overlapping clinical and biochemical presentations highlight the reliance on advanced imaging for accurate differentiation. The intricate vascularity of meningiomas, as exemplified by the encasement of critical arteries in this case, necessitates meticulous surgical technique with devascularization strategies. This successful near-complete tumor removal emphasizes the importance of such surgical expertise in navigating these diagnostically challenging sellar lesions.

Cerebral Arterial Inflow and Venous Outflow Assessment Using 4D Flow MRI in Adult and Pediatric Patients

Background and Purpose: The cerebral circulation is highly regulated to maintain brain perfusion, keeping an equilibrium between the brain tissue, cerebrospinal fluid (CSF) and blood of the arterial and venous systems. Cerebral venous drainage abnormalities have been implicated in multiple cerebrovascular diseases. The purpose of this study is to evaluate the relationship between the arterial inflow (AI) and the cerebral venous outflow (CVO) and their correlation with the cardiac outflow in healthy adults and children to understand the role of the emissary veins in normal venous drainage. Materials and Methods: A total of 31 healthy volunteers (24 adults (39.5 ± 16.0) and seven children (3.4 ± 2.2)) underwent intracranial 4D flow with full circle of Willis coverage and 2D PC-MRI at the level of the transverse sinus for measurement of the AI and CVO, respectively. The AI was calculated as the sum of the flow values in the bilateral internal carotid and basilar arteries. The CVO was calculated as the sum of the flow values in the bilateral transverse sinuses. The cardiac outflow was measured via 2D PC-MRI with retrospective ECG gating with images acquired at the proximal ascending aorta (AAo) and descending (DAo) aorta. The ratios of the AI/AAo flow and CVO/AI were calculated to characterize the fraction of cerebral arterial inflow in relation to cardiac outflow and venous blood draining through the transverse sinuses, respectively. Results: The AI and CVO were significantly correlated (r = 0.81, p < 0.001). The CVO constituted approximately 60–70% of the AI. The CVO/AI ratio was significantly lower in children versus adults (p = 0.025). In adults, the negative correlation of the AI with age remained strong (r = −0.81, p < 0.001). However, the CVO was not significantly associated with age. Conclusion: The CVO/AI ratio suggests an important role of the emissary veins, accounting for approximately 30–40% of venous drainage. The lower CVO/AI ratio in children, although partially related to decreased AI with age, suggests a greater role of the emissary veins in childhood, which strongly decreases with age.

Case Report: Delayed Cerebral Ischemia with Infarction following an Undiagnosed Aneurysmal Rupture - The Diagnostic and Management Challenge

Delayed Cerebral Ischemia (DCI) typically occurs a few days after a patient suffers subarachnoid hemorrhage and can lead to a range of poor outcomes. It is primarily driven by vasospasm and its delayed and variable presentation complicates diagnosis and treatment. Here we report a case of DCI in a 31-yearold man who presented with acute onset aphasia, right-sided weakness, and difficulty swallowing. He had experienced a severe headache accompanied by nausea and vomiting 5 days prior, with an initial NIH stroke scale score of 10. Imaging revealed a left internal carotid artery aneurysm and a watershed infarct between the anterior cerebral artery and middle cerebral artery. The patient was treated with aneurysmal coiling, intraarterial verapamil, and oral nimodipine for suspected DCI secondary to subarachnoid hemorrhage. Close monitoring of the patient and treatment led to the resolution of neurological deficits over the subsequent days., with imaging confirming reperfusion. This case presents a unique challenge due to the delayed presentation and vague history. Diagnosis and treatment of DCI following aneurysmal rupture are complicated due to its delayed and variable onset. It is crucial to consider acute aneurysmal subarachnoid hemorrhage and DCI when evaluating patients who present with multiple stroke-like symptoms over several days as the management and prognosis differ from other cases of acute ischemic stroke.

Abstract 4135790: Carotid Plaque Inflammation Is Associated with Atrial Fibrillation

Introduction: Atrial fibrillation (AF) is prevalent in patients with atherosclerotic coronary and carotid artery disease and is associated with elevated plasma inflammatory markers, such as Interleukin (IL)-6. In carotid artery atherosclerosis, macrophages are considered a local marker of inflammation. Hypothesis: We hypothesize that AF is independently associated with carotid plaque inflammation. Aims: In patients undergoing carotid endarterectomy (CEA), we aimed to determine whether carotid plaques inflammation is associated with AF. Approach: In this prospective cohort study, consecutive patients with carotid artery disease undergoing CEA were enrolled. From the plaques removed during surgery, fixed in formalin and embedded in paraffin blocks, sections were stained with antibodies against CD68 to detect macrophages (Fig.1A) . Digital copies of the slides were created by Motic Easy Scan and histologically annotated with QuPath. The percentage of CD68+ cells was defined as (CD68+ positive cells/total nuclei) x 100. Flash-frozen plaque segments were analyzed by ELISA for IL-6 concentration. Baseline demographics and clinical data, including AF diagnosis, were extracted from the electronic health records. Results: A total of 106 patients undergoing CEA, with a median age of 73 [67-78] years and comprising 83 (78.3%) males, were included in the study. AF was diagnosed prior to CEA in 13 (12.3%) patients. Univariate logistic regression showed that plaque CD68+ cell content was associated with AF (OR 1.048 [95% CI 1.010 – 1.088]; p = 0.013). Additionally, in Mann-Whitney test IL-6 levels were significantly over twofold higher in plaques of patients with AF compared to those without AF (82.4 [64.9-111.7] pg/mg vs 37.0 [18.4-93.3] pg/mg; p=0.020) (Fig. 1B) . Conclusions: The current study demonstrates an association between carotid atherosclerotic plaque macrophage content, IL6 levels and AF, supporting the role of inflammation in the pathogenesis of AF in these patients. Further studies are needed to determine the potential of plaque inflammation as a therapeutic target in AF.

Abstract 4119062: A KLF2-BMPER-Smad1/5 checkpoint regulates high fluid shear stress-mediated artery remodeling

Background: Vascular remodeling to match arterial diameter to tissue metabolic requirements commonly fails in ischemic disease. Endothelial cell (EC) sensing of elevated fluid shear stress (FSS) from blood flow induces vessel outward remodeling to restore physiological FSS, but mechanisms are poorly understood. The Smad1/5 pathway, which is maximally activated at physiological FSS and suppressed at higher flow, opposes activation of Akt, suggesting that inhibiting Smad1/5 may be required for outward remodeling. Methods: In vitro flow studies used ECs in a parallel plate flow chamber. In vivo mouse studies used a carotid-jugular fistula model to induce high flow outward remodeling in the carotid artery, and femoral artery ligation to examine recovery from ischemia and arteriogenesis in the hindlimb. Results: Suppression of Smad1/5 at high FSS is mediated KLF2-dependent induction of the BMP pathway inhibitor BMPER, which suppresses Smad1/5 and de-inhibits Akt. In a mouse arteriovenous fistula (AVF) model, high FSS induces arterial outward remodeling coincident with elevated BMPER expression and Smad1/5 inactivation. Endothelial BMPER deletion impaired blood flow recovery and vascular remodeling in the AVF and a hindlimb ischemia (HLI) model, with the latter reversed by BMP9/10 blocking antibodies (bAbs). In both STZ-induced type 1 and HFD-induced type 2 diabetic mice that show poor recovery from HLI, BMP9/10 bAbs improved outcomes. Conclusions: Suppression of Smad1/5 through a KLF2-BMPER pathway is required for high FSS-mediated outward remodeling. Mimicking this pathway with BMP9/10 antibodies improves vascular remodeling in diabetic mice, suggesting a potential new therapeutic approach for ischemic disease.

Evolocumab treatment reduces carotid intima-media thickness in paediatric patients with heterozygous familial hypercholesterolaemia.

Children with heterozygous familial hypercholesterolaemia (HeFH) show greater carotid intima-media thickness (cIMT). Evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibody, substantially reduced low-density lipoprotein cholesterol (LDL-C) and modestly reduced lipoprotein(a) in children with HeFH. We investigated evolocumab's effect on cIMT progression. HAUSER-RCT was a randomised, placebo-controlled trial. 157 paediatric patients with FH (age: 10-17 years) and LDL-C >130mg/dL despite statin therapy received monthly evolocumab 420mg or placebo for 24 weeks. Patients who continued into an open-label extension (HAUSER-OLE; n=150) received 80 weeks of monthly evolocumab plus statins. cIMT was measured by B-mode ultrasound scanning of right and left common carotid artery at baseline; week 24 of RCT [day 1 OLE]; and weeks 24, 48, and 80 of OLE. Descriptive analysis of cIMT was a prespecified HAUSER secondary endpoint, and inferential tests reported here were post-hoc. 151 patients had evaluable cIMT summary scores at ≥1 visit. From RCT baseline to week 24, mean cIMT increased by 0.006mm (SD=0.05) with placebo (n=37) and decreased by 0.003mm (SD=0.05) with evolocumab (n=76). From RCT baseline to OLE week 80, mean cIMT summary score decreased by 0.019mm (SD=0.04) and 0.012mm (SD=0.05), respectively, in patients who initially received placebo (n=34, P=0.007) versus receiving evolocumab throughout (n=59, P=0.067). Across patients who received evolocumab in OLE, mean cIMT significantly decreased by 0.011mm (SD=0.05) from OLE day 1 to week 80 (n=94, P=0.034). In children with HeFH, evolocumab plus statin treatment up to 104 weeks led to regression in carotid arterial wall thickening.

Abstract 4118076: Right Innominate Artery Endovascular Intervention Via Single Radial Access and Use Of Embolic Protection

Introduction: The occurrence of innominate artery stenosis is less prevalent compared to subclavian artery disease. Small studies suggest up to 8% of individuals initially diagnosed with suspected subclavian steal syndrome may present with innominate artery lesions. Deployment of an embolic protection filter within the internal carotid artery during percutaneous intervention of the innominate artery presents a solution to mitigate embolism. Case: A 70-year-old female with a history of peripheral vascular disease presented with claudication in both arms, manifested as pain in both arms. Her left subclavian was stented months prior to presentation. An aortogram revealed severe stenosis of the innominate artery (Figure 1). Since multiple attempts to cross the lesion antegrade from the femoral access site were unsuccessful, we proceeded with the successful deployment of an embolic protection filter in the right internal carotid artery via our right radial artery access site (Figure 2). Using the right radial artery, we passed a long run-through guidewire into the distal abdominal aorta. Due to severe aortic tortuosity, we were unable to snare the wire from the aorta. Therefore, we upsized the radial sheath to 7 French over both wires (runthrough and bare). Using a support catheter, we exchanged the runthrough wire for a Glidewire Advantage. We advanced an 8 x 29mm balloon expandable stent to the area of innominate stenosis and deployed it (Figure 3). We postdilated the stent with a 14mm balloon. Angiography demonstrated adequate expansion. On follow up, the patient was without claudication and had triphasic flow in the innominate and left subclavian arteries. Discussion: Treating innominate artery stenosis via radial access employing a sole entry point for both embolic protection and treatment administration offers a substitute where additional access is infeasible. Modern embolic protection techniques are superior due to their flexibility and ease of use. In this case, placing the embolic protection device in the carotid artery was mandatory through the sole radial access to prevent trapping the filter behind the innominate artery stent. We were able to perform both the embolic device placement and the stenting with the same radial access. Conclusion: Endovascular intervention of innominate artery stenosis via radial access, utilizing a single radial access for both embolic protection and treatment delivery, presents an alternative when femoral access is not feasible.

Abstract 4122092: Carotid plaque progression predicts persistent endothelial dysfunction in an infarct-related coronary artery in STEMI survivors

Background and Aim: Persistent coronary endothelial vasomotor dysfunction predicts future coronary events; however, performing multiple invasive endothelial function tests is difficult in actual clinical practice. This study examined whether carotid plaque changes can predict persistent coronary endothelial dysfunction using serial assessments of the coronary vasomotor response to acetylcholine (ACh) in the infarct-related artery (IRA) among patients with ST-elevation acute myocardial infarction (STEMI). Methods: This study included 169 consecutive patients with a first acute STEMI due to the left anterior descending coronary artery (LAD) occlusion who underwent successful reperfusion therapy with percutaneous coronary intervention. The vasomotor response to ACh in the LAD was measured within two weeks of acute myocardial infarction (AMI) (first test) and repeated at six months (second test) after AMI under optimal anti-atherosclerotic therapy. Ultrasonography of the bilateral common carotid artery (CCA) and internal carotid artery (ICA) was performed during the acute phase, and the thickest intima media thickness (IMT) of either artery was measured as the maximum IMT. After six months, the IMT at the site of maximal IMT was measured to determine whether there was an increase or decrease in IMT. Results: Finally, 87 STEMI patients analyzed in this study. At 6 months, 25 patients (28.7%) showed carotid plaque progression. In a multivariable adjusted analysis, carotid plaque progression was identified as an independent predictor of persistent coronary endothelial dysfunction, both in terms of coronary diameter response [OR 3.22, 95% confidence interval1.13 - 9.15, P = 0.03] and coronary flow response [OR 2.65, 95% confidence interval 1.01 - 7.00, P = 0.04]. Conclusions: Carotid plaque progression could independently predict persistent endothelial vasomotor dysfunction in the IRA of STEMI survivors.

Abstract 4124084: Nitric Oxide Releasing Bionanomatrix Gel For Dialysis Arteriovenous Fistula Maturation

Introduction: About 600,000 patients in the US suffer from end-stage renal disease (ESRD); more than 75% of ESRD patients undergo dialysis. Vascular access dysfunction is a major cause of morbidity and hospitalization in dialysis patients. Arteriovenous fistulas (AVFs) are considered the gold standard of vascular access for dialysis. However, about 60% of AVFs fail to mature because of early venous neointimal development and poor vasodilation and vascular wall remodeling. Therefore, to promote AVF maturation, we propose the application of a nitric oxide (NO) releasing nanomatrix gel, or ‘NO gel’, on the created AVF. The NO gel is composed of peptide amphiphiles (PA), which contain a polylysine (KKKKK) group to form NO-donating residues. In this study, we test our hypothesis that the NO gel applied at AVF can promote AVF maturation by decreasing venous intimal hyperplasia, enhancing vasodilation and vascular outward remodeling in porcine model. Materials and Methods: PA containing with KKKKK was synthesized and charged with NO to produce NO gel. For in vivo studies, AVFs in porcine were created by connecting the jugular vein and carotid artery. The NO gel was applied perivascularly over the AVF anastomosis. And the pigs were sacrifice after 35 days. AVF hemodynamics were evaluated using MRI-based computed fluid dynamics analysis. Results: We found significant decrease in neointimal hyperplasia in porcine AVFs treated with NO gel compared to the control groups. Additionally, the percentage of open lumens was significantly higher in the NO gel-treated group. It is indicated that veins in NO treated group showed less fibrosis as an less type I collagen I produced in the NO treated group than control. Also, the NO gel significantly improved hemodynamics and vascular remodeling of porcine AVFs compared to the control. Conclusion: These results suggest that the NO gel plays a crucial role in AVF maturation by reducing intimal hyperplasia and stenosis following AVF creation in a pig model. When intimal hyperplasia is reduced and the vessel is dilated, less tensile force of blood flow is applied on the arterialized vein, directing the AVF to appropriate maturation.

Improving arterial stiffness prediction with machine learning utilizing hemodynamics and biomechanical features derived from phase contrast magnetic resonance imaging.

Arterial stiffness has emerged as a prominent marker of risk for cardiovascular diseases. Few studies are interested in predicting symptomatic or asymptomatic arterial stiffness from hemodynamics and biomechanics parameters. Machine learning models can be used as an intelligent tool for arterial stiffness detection based on hemodynamic and biomechanical parameters. Indeed, in the case of arterial stiffness hemodynamics and biomechanics parameters present significant change, such as an increase in age, local wave velocity, arterial elastance, Young's modulus, reflected wave amplitude, decrease in arterial compliance, reflected wave arrival time, and reflection coefficient. This study aims to assess the impact of artificial intelligence using machine-learning algorithms for the detection of arterial stiffness. The ability of various machine-learning approaches can be investigated to predict wall stiffness in the carotid artery and to evaluate the risk of cardiovascular events. A mathematical model developed in previous work was used to determine hemodynamic and biomechanical parameters. Accuracy, sensitivity, and specificity are calculated to evaluate the performance of the proposed models. All used classifiers demonstrated high performance in predicting arterial stiffness, notably with the Support Vector Machine, Artificial Neural Network, and Decision Tree classifiers achieving exceptional accuracies of 100%. In this study, the potential of machine learning based on hemodynamic parameters for the prediction of symptomatic and asymptomatic arterial stiffness was demonstrated.

The Impact of the Histone Deacetylase Inhibitor-Sodium Butyrate on Complement-Mediated Synapse Loss in a Rat Model of Neonatal Hypoxia-Ischemia.

Perinatal asphyxia is one of the most important causes of morbidity and mortality in newborns. One of the key pathogenic factors in hypoxic-ischemic (HI) brain injury is the inflammatory reaction including complement system activation. Over-activated complement stimulates cells to release inflammatory molecules and is involved in the post-ischemic degradation of synaptic connections. On the other hand, complement is also involved in regenerative processes. The histone deacetylase inhibitor (HDACi)-sodium butyrate (SB)-provides reduction of inflammation by decreasing the expression of the proinflammatory factors. The main purpose of this study was to examine the effect of SB treatment on complement activation and synapse elimination after HI. Neonatal HI was induced in Wistar rats pups by unilateral ligation of the common carotid artery followed by 60-min hypoxia (7.6% O2). SB (300mg/kg) was administered on a 5-day regimen. Our study has shown decreased levels of synapsin I, synaptophysin, and PSD-95 in the hypoxic-ischemic hemisphere, indicating synaptic loss after neonatal HI. Transmission electron microscopy revealed injury of the synaptic structures in the brain after HI. SB treatment increased the level of the synaptic proteins, improved tissue ultrastructure, and reduced degradation of the synapses. Neonatal HI induced mRNA expression of the complement C1q, C3, C5, and C9, and their receptors C3aR and C5aR. The effect of SB was different depending on the time after induction of hypoxic-ischemic damage. Our study demonstrated that neuroprotective effect of SB may be related to the modulation of complement activity after HI brain injury.

Abstract 4132968: CCR5 modulation enhances M-MDSCs functionality in early atherosclerosis

Background: The role of immune suppressive microenvironment, promulgated by the presence of Myeloid Derived Suppressor Cells (MDSC) have been the major focus of research delineating the underlying mechanisms of cardiovascular diseases (CVD). CCR5, a chemokine receptor, has been associated with both immunosuppressive and inflammatory phenotypes, however, the possible role of CCR5 pertaining to MDSCs in the development of atherosclerosis has not been elucidated yet. Therefore, we investigated the therapeutic potential of CCR5 modulation in early atherosclerosis progression. Methods: CCR5 receptor-ligand expression was studied with flow cytometry, real time PCR and immunocytochemistry in 65 individuals (25 Healthy controls, 20 young hypercholesterolemic individuals, and 20 stable [Coronary Artery Disease] CAD patients). To induce atherosclerosis, mice were fed high fat diet (HFD) for 6 weeks following partial ligation of left carotid artery in C57BL6 mice. MDSCs phenotype and functionality were assessed using CCR5 inhibitor in vitro (10 -8 M) and in vivo (i.p 3ng/day for 15 days) . M-MDSCs phenotype switch, atherosclerotic lesion development and plaque phenotype was studied in vivo . Results: We observed CCR5 elevation on Monocytic-MDSCs in the early phase of atherosclerosis. M-MDSCs displayed an intermediate phenotype with expression of both pro and anti-inflammatory mediators in early atherosclerosis, a similar trend was observed in inflammatory cytokines stimulated M-MDSCs ( in vitro ). Notably, DAPTA treatment shifted phenotype of M-MDSCs to anti-inflammatory profile with elevated expression of IL-10 and reduced expression of IFNγ, IL4, and IL22. Further, CCR5 modulation expanded IL10+M-MDSC in vivo . Additionally, DAPTA reduced the migratory potential, reduced cholesterol uptake and improved the functionality (suppression of T cell) of M-MDSCs. Blocking CCR5 with DAPTA led to the formation of stable plaque in HFD-fed mice. Conclusion: Increased expression of CCR5 coupled with inflammatory cytokine secretion by regulatory cells lead to dysfunctional M-MDSCs in CVD risk factor population. Possibly this dysfunctionality contributes to the development and progression of CVD including atherosclerosis. Our findings show targeting of CCR5 with DAPTA reduces atherogenesis, increases plaque stabilization and corrects phenotypic alterations in immune suppressive M-MDSCs. The functionality and phenotype of M-MDSCs in atherosclerosis, may be ameliorated by targeting CCR5.

Correlation between nova volume flow rate and TOF signal intensity ratio: value in unilateral internal carotid artery occlusion.

Non-invasive optimal vessel analysis quantitative magnetic resonance angiography (NOVA-QMRA) has emerged as a valuable tool to characterize cerebral hemodynamics in intracranial atherosclerotic disease (ICAD). Our aim was to explore the eventual correlation between volume flow rate (VFR) measured via NOVA-QMRA and signal intensity ratio (SIR) of time-of-flight (TOF) MRA in M1- and P2-segments bilaterally in patients with unilateral internal carotid artery (ICA) occlusion. Patients with acute, subacute or chronic unilaterall ICA occlusion receiving NOVA-QMRA between June 2019 and June 2021 were retrospectively included. In bilateral M1- and P2-segments VFR was assessed by means of NOVA-QMRA and a region of interest (ROI) was selected to measure TOF SIR. A correlation between TOF SIR and VFR was tested by means of Pearson correlation coefficient. Mean difference of TOF SIR and VFR between ipsilateral (to occluded ICA) and contralateral M1- and P2-segments was analyzed using a two-sided Welch's t test. Fifty-five patients with unilateral ICA occlusion were included (acute: 28; subacute: 8; chronic: 19). Both ipsilateral (r = 0.536, p < 0.001) and contralateral (r = 0.757, p < 0.001) TOF SIR correlated significantly with NOVA VFR. This observation proved especially true for patients with chronic ICA occlusion. Both VFR (165.18 vs 110.60, p < 0.001) and TOF SIR (4.96 vs 2.70, p < 0.001) were higher in contralateral than ipsilateral M1-segments; whereas, the contrary was observed for P2-segments (VFR 72.35 vs 102.12, p < 0.001, TOF SIR 2.87 vs 3.39, p = 0.016). The study results showed that TOF SIR significantly correlated with phase-contrast derived flow volume in patients with symptomatic ICA occlusion. This correlation remains the same regardless of the stage of the ischemic stroke (acute vs subacute vs chronic). Furthermore, significantly high VFR and TOF SIR in ipsilateral P2-segments may provide evidence of leptomeningeal collateralization in acute patients. Standardly performed TOF SIR Sequences might be of help for a qualitative evaluation of the flow in M1- and P2-segments in patients with unilateral ICA occlusions. NOVA QMRA allows precise quantitative measurements of the flow in cerebral vessels.

Metabolomic study for the identification of symptomatic carotid plaque biomarkers

Carotid artery stenosis is mainly produced due to the progressive accumulation of atherosclerotic plaque in the vascular wall. The atherosclerotic plaque is characterized by the accumulation of lipids, low density proteins, expression of chemokines and adhesion molecules, and migration of monocytes and lymphocytes into the plaque. Its rupture can produce stroke, but embolic propensity depends principally on the composition and vulnerability of plaque rather than the severity of stenosis. It is important, then, to ascertain which patients with carotid artery stenosis have a greater risk of developing neurological symptomatology. Here, we present a metabolomic study by using nuclear magnetic resonance (NMR) spectroscopy in atheroma plaque and serum samples from patients with recently symptomatic and asymptomatic carotid stenosis to search for metabolites that could be used as biomarkers associated with plaque vulnerability and subsequent risk of rupture. Thirty-eight atheromatous plaque samples (24 asymptomatic patients and 14 symptomatic) and 70 serum samples (43 asymptomatic and 27 symptomatic) were studied by NMR spectroscopy. The data were analysed using multivariate statistics (PLS-DA) to determine a model to discriminate between symptomatic and asymptomatic samples (atheroma plaques and sera). The calculated PLS-DA models showed a 100 % sensitivity and a 96.6 % specificity for the cross validation to discriminate between symptomatic and asymptomatic plaques, and 88.37 % sensitivity and 77.78 % specificity when serum samples were analysed. According to the results of our multivariate and univariate analysis, the most discriminative metabolites for plaque vulnerability were threonine in serum samples, and glutamate in plaque samples. Also, an analysis of the main metabolic pathways involved in plaque vulnerability revealed that d-glutamine and d-glutamate metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis were the most affected pathways in plaque and serum, respectively.

Abstract 4143225: Carotid Artery Ultrasound Grayscale and Incident Dementia: The Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: Vascular contributions to cognitive impairment and dementia are potentially modifiable. Early detection of reversible arterial injury may improve dementia risk stratification and provide an opportunity for treatment monitoring. We hypothesized that carotid ultrasound grayscale-median (GSM), a novel imaging biomarker of early arterial injury, would predict incident all-cause dementia in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: The MESA enrolled adults aged 45-84 years old who were free of atherosclerotic cardiovascular disease at baseline. Common carotid artery GSM (grayscale units) was measured at baseline. Incident all-cause dementia events were identified by hospital and death records. Adjusted Cox proportional hazards models with natural cubic splines allowing for non-linear effects investigated the associations of baseline GSM and incident all-cause dementia. Results: The 1,788 participants were a mean (standard deviation) 63.1 (10.3) years old (53% female). Over a median of 13.7 years, 157 all-cause dementia events occurred. Lower (worse) carotid GSM independently predicted incident all-cause dementia (Hazard Ratio [HR] 1st to 3rd tertile, 1.39 [95% Confidence Intervals, 1.08-1.80], p =0.04). In models adjusting additionally for carotid IMT there was no attenuation of the association of GSM and incident all-cause dementia (HR 1.63 [95% CI 1.13-2.35], p=0.033) (Figure 1). Conclusions: Lower GSM predicts incident all-cause dementia independent of carotid intima-media thickness, suggesting it may serve as an early marker of dementia risk.

Abstract 4115642: Resonance Sonomanometry in an Early Prototype Device Effectively Measures Continuous, Noninvasive Blood Pressure

Background: Nearly half of American adults have hypertension; however, reliable, continuous, noninvasive blood pressure (BP) measurement (cNIBP) for inpatient and outpatient use is not currently available. This study evaluated a new method for cNIBP measurement called resonance sonomanometry (RSM). RSM derives blood pressure using first-principles physics, is applicable to any artery, and requires no calibration, blood vessel deformation, or dependence on demographic inputs. Methods: A prospective, observational feasibility study was undertaken to compare carotid artery BP measurements with a prototype ultrasound-based cNIBP device incorporating RSM, to arterial catheter BP measurements in the radial arteries of 60 test subjects. Catheter measurements were obtained from a distal peripheral artery (radial), oscillometric cuff from the brachial artery, and RSM was obtained from a central artery (carotid). This study was the first-in-human study for the RSM method in comparison to arterial catheters. Results: RSM-induced arterial resonance was observed in all tested subjects. For each of the subjects, the arterial resonant frequency increased with increasing BP during systole, and decreased with diastole (consistent with the cardiac cycle), as predicted by the physical model. RSM-derived BP traces were qualitatively similar to catheter data, exhibiting features such as the dicrotic notch. The RSM method yielded similar diastolic BP (DBP), but lower systolic BP (SBP) compared to the arterial catheter, likely due to expected peripheral pulse amplification. RSM DBP was not significantly different from the catheter (+1.5mmHg, p = 0.187), while BP cuff DBP was significantly different from the catheter (−4.3mmHg, p=0.002). There were significant differences in the catheter to RSM SBP (34.1 mmHg, p &lt; 0.01), consistent with the aforementioned expectations from a central-versus-peripheral continuous pressure measurement. Conclusions: RSM is a novel BP measurement technique that could enable cNIBP measurements with accuracy required in hospitals. While the data are promising, significant future work remains. The study was meant to test the RSM method, not the device or form factor. Consequently, the form factor will need to be improved prior to clinical use. The prototype was designed for manual operation; thus, future work will also be needed to enhance the ability of the device to autonomously locate and track the artery for ease of use.

Co-administration of dexmedetomidine with total intravenous anaesthesia in carotid endarterectomy reduces requirements for propofol and improves haemodynamic stability: A single-centre, prospective, randomised controlled trial.

Total intravenous anaesthesia guided by electroencephalography and neurophysiological monitoring may be used for carotid endarterectomy. Reduction of brain metabolic demand during cross-clamping of the internal carotid artery with propofol titrated to burst suppression requires effect-site concentrations that may delay emergence and interfere with intraoperative neurophysiological monitoring. To test the hypothesis that dexmedetomidine decreases the effect-site concentration of propofol required for burst-suppression in patients undergoing carotid endarterectomy. Randomised controlled trial. Patients undergoing carotid endarterectomy. University Hospital of Berne, Switzerland, from October 2018 to September 2024. Patients were randomised into a control (n = 23) and a dexmedetomidine groups (n = 22). Total intravenous anaesthesia was administered to both groups. Patients in the dexmedetomidine group received an intravenous bolus of dexmedetomidine (0.4 μg kg-1 over 10 min) before induction, followed by a continuous intravenous infusion (0.4 μg kg-1 h-1). The effect-site concentrations of propofol were titrated against frontal electroencephalography parameters. Burst suppression was induced with propofol during cross-clamping of the internal carotid artery. The primary outcome was the effect-site concentration of propofol required for burst-suppression. The secondary outcomes were the requirement for vasoactive substances, neurophysiological monitoring parameters, and postoperative delirium. The effect-site concentration of propofol required for burst suppression was 4.0 μg ml-1 [3.50 to 4.90] (median [interquartile range]) in the dexmedetomidine group compared with 6.0 μg ml-1 [5.5 to 7.3] in the control group (P < 0.001). Less norepinephrine was required in the dexmedetomidine group (total 454 μg [246 to 818] compared with 1000 μg [444 to 1326] (P = 0.015) in the control group). Dexmedetomidine did not affect intraoperative neurophysiological monitoring. Co-administration of dexmedetomidine to total intravenous anaesthesia for carotid endarterectomy decreased the effect-site concentrations of propofol required for burst suppression by 33%. The propofol-sparing effect and peripheral alpha-agonism of dexmedetomidine may explain the reduced requirement for vasopressors. Clinicaltrials.gov identifier: NCT04662177.