Vessel Wall Research Articles

Assessing Changes in Vascular Inflammation and Urate Deposition in the Vasculature of Gout Patients After Administration of Pegloticase Using Positron Emission Tomography and Dual-Energy Computed Tomography—A Pilot Study

We assessed changes in vascular inflammation and monosodium urate (MSU)-coded deposits after administration of Pegloticase in the vasculature of tophaceous gout patients using 18F-fluorodeoxyglucose (18F-FDG) Positron emission tomography/computed tomography (PET/CT) and dual-energy CT (DECT). Ten patients with tophaceous gout, intolerant or refractory to urate-lowering therapy (ULT), were treated with Pegloticase every two weeks for six months. 18F-FDG PET/CT and DECT were performed at baseline and after Pegloticase therapy to detect vessel wall inflammation (Standard uptake value, SUVmean, and SUVmax) and vascular MSU-coded deposition (MSU volume). Data were summarized using means and standard deviations. Baseline and follow-up values were compared for each variable using mixed-effect models. Significant decreases in SUVmean (p = 0.0003) and SUVmax (p = 0.009) were found with a trend towards a decrease in vessel wall MSU volume after treatment. There was a significant decrease in serum urate, correlating with reduction in SUVmean (R2 = 0.65), with a trend towards a decrease in CRP and blood pressure in all patients. Despite the small sample size, we were able to demonstrate a decrease in vessel wall inflammation and a trend towards a decrease in MSU volume by intensively lowering serum urate. These findings suggest that MSU-coded deposits and hyperuricemia may play a role in vascular wall inflammation. It remains to be seen whether this correlates with a decrease in adverse cardiovascular outcomes.

Varicella zoster vasculopathy causing recurrent ischaemic strokes in an immunocompetent patient.

A 66-year-old woman reported 10 days of generalised weakness, falls and memory 'glitches'. She had developed left-sided ophthalmic herpes zoster 3 months before but was otherwise well. MR scan of brain showed acute left-sided ischaemic strokes and CT cerebral angiogram identified marked stenoses of the left anterior and middle cerebral arteries. We suspected varicella-zoster virus vasculopathy, confirmed by cerebrospinal fluid analysis. Initially she had further ischaemic strokes despite intravenous acyclovir, prednisone, aspirin and clopidogrel. However, after prolonged acyclovir and prednisone, there were no new infarcts though imaging of left anterior and middle cerebral artery vessel walls showed persistent inflammation. Varicella zoster vasculopathy can cause recurrent ischaemic strokes, even in immunocompetent people with no cardiovascular risk factors, and despite long-term antiviral therapy.

The Correlation of Vessel Wall Macrophage Infiltration with Hemosiderin in Arteriovenous Malformations

Endothelial dysfunction, induced by high shear stress from increased nidal blood flow, may promote a cycle of inflammation, possibly leading to instability and cerebral arteriovenous malformations (AVMs) rupture. Macrophages, identified with CD68, are key inflammatory components in AVM pathology. We aim to evaluate the relationship of inflammation with AVM flow and hemosiderin. This is a retrospective study of archived tissue. Adult patients (2002-2022) with baseline quantitative magnetic resonance angiography (QMRA) imaging, no embolization, and history of microsurgical resection (n=17), with both ruptured (n=9) and unruptured cases (n=8). Brain AVM sections were stained with CD68 to quantify vessel wall macrophage infiltration and hematoxylin and eosin stain as a control and to quantify hemosiderin. QMRA with noninvasive optimal vessel analysis (NOVA) was reviewed, and AVM flow was calculated. Statistical analyses were performed. There were no significant differences between macrophage infiltration and patient demographics, Spetzler-Martin grade, eloquence, venous stenosis, nidus compactness, volume, and AVM flow. Vessel wall macrophage infiltration positively correlated with patients who presented with confirmed AVM rupture (163.8 +/- 46.7 vs. 101.3 +/- 49.4, p=0.017). Increases in vessel wall macrophage infiltration were found to positively correlate with higher grades of hemosiderin (p=0.023), except for grade 4 hemosiderin. Venous anomaly showed a negative association with macrophage infiltration (p=0.035). These findings suggest a relationship between AVM vessel wall inflammation, hemosiderin, and hemorrhage presentation. Further investigations with larger sample sizes are warranted to understand the role of altered hemodynamics, hemosiderin deposition and inflammation in AVM vessel walls.

Further validating the robotic microsurgery platform through preclinical studies on rat femoral artery and vein.

Introduction This research aims to validate the proficiency and accuracy of the robotic microsurgery platform using rat femoral vessel model. Materials and Methods Total of 256 rat femoral vessels were performed, half using robotic and the other by manual microanastomosis by 8 microsurgeons with less than 5 years of experience given 8 trials (rats) each. Vessel demographics, proficiency (duration of suture and Structured Assessment of Robotic Microsurgical Skills (SARMS)) and accuracy (patency and Scanning Electron Microscopic (SEM)) was analyzed between the two groups. Results Using the robot, an average of 4 trials was needed to reach a plateau in total anastomosis time and patency. Significant more time was required for each vessel anastomosis (34.33 versus 21.63 minutes on the 8th trial, p<0.001) one factor being higher number of sutures compared to the hand-sewn group (artery: 7.86±0.51 versus 5.86±0.67, p=0.035, vein: 12.63±0.49 versus 9.57±0.99, p=0.055). The SARMS scores became nonsignificant between the two group on the 4th trial. The SEM showed higher tendency of unevenly spaced sutures, infolding, tears in the vessel wall for the hand-sewn group. Conclusion Using the robot, similar patency, accuracy, and proficiency can be reached through fast but steep learning process within 4 trials (anastomosis of 8 vessels) as the hand-sewn group. The robotic anastomosis may take longer time, but this is due to the increased number of sutures reflecting higher precision and accuracy. Further insight of precision and accuracy was found through the SEM demonstrating the possibility of the robot to prevent unexpected and unwanted complications.

Simulation-based optimization and experimental comparison of intracranial T2-weighted DANTE-SPACE vessel wall imaging at 3T and 7T.

T2-weighted DANTE-SPACE (Delay Alternating with Nutation for Tailored Excitation - Sampling Perfection with Application optimized Contrasts using different flip angle Evolution) sequences facilitate non-invasive intracranial vessel wall imaging at 7T through simultaneous suppression of blood and CSF. However, the achieved vessel wall delineation depends closely on the selected sequence parameters, and little information is available about the performance of the sequence using more widely available 3T MRI. Therefore, in this paper a comprehensive DANTE-SPACE simulation framework is used for the optimization and quantitative comparison of T2-weighted DANTE-SPACE at both 7T and 3T. Simulations are used to propose optimized sequence parameters at both 3T and 7T. At 7T, an additional protocol which uses a parallel transmission (pTx) shim during the DANTE preparation for improved suppression of inflowing blood is also proposed. Data at both field strengths using optimized and literature protocols are acquired and quantitatively compared in six healthy volunteers. At 7T, more vessel wall signal can be retained while still achieving sufficient CSF suppression by using fewer DANTE pulses than described in previous implementations. The use of a pTx shim during DANTE at 7T provides a modest further improvement to the inner vessel wall delineation. At 3T, aggressive DANTE preparation is required to achieve CSF suppression, resulting in reduced vessel wall signal. As a result, the achievable vessel wall definition at 3T is around half that of 7T. Simulation-based optimization of DANTE parameters facilitates improved T2-weighted DANTE-SPACE contrasts at 7T. The improved vessel definition of T2-weighted DANTE-SPACE at 7T makes DANTE preparation more suitable for T2-weighted VWI at 7T than at 3T.

Protective effect of 6'-Sialyllactose on LPS-induced macrophage inflammation via regulating Nrf2-mediated oxidative stress and inflammatory signaling pathways.

Macrophages play a central role in cardiovascular diseases, like atherosclerosis, by accumulating in vessel walls and inducing sustained local inflammation marked by the release of chemokines, cytokines, and matrix-degrading enzymes. Recent studies indicate that 6'-sialyllactose (6'-SL) may mitigate inflammation by modulating the immune system. Here, we examined the impact of 6'-SL on lipopolysaccharide (LPS)-induced acute inflammation using RAW 264.7 cells and a mouse model. In vivo, ICR mice received pretreatment with 100 mg/kg 6'-SL for 2 h, followed by intraperitoneal LPS injection (10 mg/kg) for 6 h. In vitro, RAW 264.7 cells were preincubated with 6'-SL before LPS stimulation. Mechanistic insights were gained though Western blotting, qRT-PCR, and immunofluorescence analysis, while reactive oxygen species (ROS) production was assessed via DHE assay. 6'-SL effectively attenuated LPS-induced p38 MAPK and Akt phosphorylation, as well as p65 nuclear translocation. Additionally, 6'-SL inhibited LPS-induced expression of tissue damage marker MMP9, IL-1β, and MCP-1 by modulating NF-κB activation. It also reduced ROS levels, mediated by p38 MAPK and Akt pathways. Moreover, 6'-SL restored LPS-suppressed Nrf2 and HO-1 akin to specific inhibitors SB203580 and LY294002. Consistent with in vitro results, 6'-SL decreased oxidative stress, MMP9, and MCP-1 expression in mouse endothelium following LPS-induced macrophage activation. In summary, our findings suggest that 6'-SL holds promise in mitigating atherosclerosis by dampening LPS-induced acute macrophage inflammation.

Blood flow through a stenosed left anterior descending coronary artery: Evaluation of loss coefficients in one-dimensional fluid–structure interaction model

Coronary arterial flow is affected by conditions such as atherosclerosis and stenosis resulting in coronary artery disease. Quantifying the flow fields across arteries is a key aspect in the functional assessment of occlusive arterial disease. An essential aspect of blood flow modeling is the mechanical interaction between the fluid flow and the arterial vessel wall. The present study focuses on the modeling of blood flow within the left anterior descending artery affected with stenosis. A one-dimensional (1D) model was developed to study the transient blood flow characteristics in the artery. The 1D model is coupled with the material tube law to account for the flexibility of the arterial wall. The loss coefficients that account for the local viscous and turbulent losses across the stenosis region are estimated accurately in terms of the varying local cross-sectional area, instead of empirical constants used in the literature. It was observed that the magnitude of viscous losses decreases with an increase in the severity of stenosis. For lower degree of stenosis (&amp;lt;30%), the local turbulent losses are insignificant compared to the viscous losses. The maximum deformation of the vessel wall is ∼0.12mm at t=0.45s for s=70%. During the cardiac cycle (T=0.9s), the artery is observed to be experiencing dilation (Δr&amp;gt;0) in the upstream region, whereas contraction (Δr&amp;lt;0) in the downstream region for all the values of severity (s). A fractional flow reserve of 58.53% was noticed in a stenosed artery of 70% severity.

POLYCORE: Polygon-based contour refinement for improved Intravascular Ultrasound Segmentation

Segmentation of the coronary vessel wall in intravascular ultrasound is a fundamental step in guiding coronary intervention. However, it is an challenging task, even for highly skilled cardiologists, due to image artefacts and shadowed regions caused by calcified plaque, guide wires and vessel side branches. Recently, dense-based neural networks have been applied to this task, however, they often fail to predict anatomically plausible contours in these low-signal areas. We propose a novel methodology called Polygon-based Contour Refiner (POLYCORE) that addresses topological error in dense-based segmentation networks using a relational inductive bias through higher-order connections between vertices to learn anatomically rational contours. Our approach remedies the over-smoothing phenomena common in polygon networks by introducing a new vector field refinement module which enables pixel-level detail to be added in an iterative process. POLYCORE is enhanced with augmented polygon aggregation which we show is more effective than typical dense-based test-time augmentation strategies. We achieve state-of-the-art results on two diverse datasets, observing particular improvements when segmenting the lumen structure and in topologically-challenging regions containing shadow artefacts. Our source code is available here: http://orcid.org/https://github.com/kitbransby/POLYCORE.

Transient Perivascular Inflammation of the Carotid Artery Syndrome: A Case Report with Diagnostic Insights from Vessel Wall Imaging and Contrast-enhanced Ultrasonography

Transient perivascular inflammation of the carotid artery (TIPIC) syndrome is a rare disease accompanied by acute neck pain and specific pathologic changes in the carotid artery and surrounding tissue. Here, we present a case diagnosed with typical imaging features, including extensive enhancement with luminal narrowing on vessel wall imaging and the presence of microbubbles on contrast-enhanced ultrasonography. These findings provide valuable insights into the pathophysiology of TIPIC syndrome and importance of imaging modalities for early detection and management.

Coronary Artery Vasculitis and Encasement: Multimodality Imaging Findings and Mimics.

Coronary artery vasculitis (CAV) and coronary artery encasement are rarely diagnosed conditions that are important diagnostic considerations, particularly in patients with acute coronary syndrome without traditional cardiovascular risk factors or systemic illness. Vasculitis refers to inflammation of the blood vessel walls, which can be primary or secondary. This process should be distinguished from neoplastic involvement of the coronary arteries, termed coronary artery encasement. Prospective diagnosis of these diseases is challenging, often requiring multidisciplinary workup with careful attention to clinical presentation and multiorgan findings. While CAV and coronary artery encasement can be indistinguishable at coronary CT angiography, certain imaging features help order the differential diagnosis. CAV should be considered when there is smooth wall thickening that is circumferential and/or continuous. A diagnosis of coronary artery encasement is favored when there is irregular or nodular wall thickening that is eccentric to the vessel lumen. Epicardial fat stranding may also appear more extensive compared with CAV. Potential mimics of CAV include atherosclerosis, acute plaque rupture, coronary artery aneurysm, and spontaneous coronary artery dissection. Detection and diagnosis of CAV may help avoid complications related to accelerated atherosclerosis and infarction. Radiologists should be familiar with the range of pathologic conditions that can affect the coronary arteries beyond atherosclerosis as they may be the first to raise such diagnostic possibilities, guiding next steps in patient workup and management. ©RSNA, 2024 Supplemental material is available for this article.

Label-free classification of atherosclerosis plaque via OCT and ultraviolet autofluorescence spectroscopy

We proposed a label-free method for the identification and classification of atherosclerosis plaques by combining optical coherence tomography (OCT) with ultraviolet autofluorescence spectroscopy (uFLS). By aligning the OCT source and the FLS excitation beams, we were able to illuminate the same spot on plaques fixed to the integrated probe, which underwent rotational scanning. This setup enabled the detection of both OCT images and uFLS spectra of the plaques in a co-localized manner. In our approach, a 1300 nm centered swept laser source was utilized for OCT imaging, while a 355 nm laser source, along with a lensed multimode fiber, served as the fluorescence probe for uFLS. The successful acquisition of OCT-uFLS images provided complementary information regarding the tomographic internal structure and biochemical components within the vessels, allowing for comprehensive identification and classification of atherosclerosis plaques. Furthermore, we achieved quantitative measurements and analysis of fluorescence spectra from three main component channels, corresponding to collagen, elastin, and lipid. This enabled us to differentiate atherosclerosis from normal vessel walls and determine the specific types. With the implementation of this dual-modal OCT-uFLS technique, it is possible to facilitate the label-free classification of various histopathological types of atherosclerosis plaques, which holds the potential for both diagnosis and image-guided ablation therapy applications.

Variance investigation on the microstructural characteristics of vessels among three lignocellulosic biomasses

Especially, the processing and utilization of biomass-based material is closely related to the vessel, e.g. the flow of vapour and additive. It is conventional that vessels in most plants can influence on water and nutrients transport between adjacent cells, which could just infer to be important in the wood-based panel industries. In this work, a complete characterization of vessels and pits is presented for three conventional biomasses in wood-based panel: poplar (Populus deltoides) (P), moso bamboo (Phyllostachys edulis) (B), and the fruit shell of oil camellia (Camellia Oleifera) (FS_OC). Every material is analyzed by combining several techniques including: light microscopy, scanning electron microscopy and surveying calculations from resin casting. The results show that among the three biomass materials, B has a significantly larger vessel width (164.8 ± 6.0 μm for B, 2.2 ± 6.2 μm for P, 10.0 ± 0.8 μm for FS_OC) and smaller inclination angle of the perforation plates (6.8° for B, 44.7° for P), which is more conductive to improving moisture transfer between the vessels. The vessel length of P varies widely from 676.8 μm to 1025.2 μm, which is related to its seasonal growth. By resin casting analysis, more differences in the morphology and distribution of pits in the vessel walls were observed between the three species. Such as, For B, there are numerous pits between vessel cells, while very few to none between vessel and parenchyma cells or fiber. In addition to pits, B and FS_OC also have spiral thickening structures on their vessel walls. The pit membrane is an elliptical shape in P, while slit-like shape in FS_OC and a combination of both elliptical and slit-like shape in bamboo. The unique microstructural characteristics of vessels is related to the individual plant growth traits, which is the basis for biomass-based material processing and utilization.

Exposure to air pollutants and subclinical carotid atherosclerosis measured by magnetic resonance imaging: A cross-sectional analysis.

Long-term exposure to air pollution has been associated with higher risk of cardiovascular mortality. Less is known about the association of air pollution with initial development of cardiovascular disease. Herein, the association between low-level exposure to air pollutants and subclinical carotid atherosclerosis in adults without known clinical cardiovascular disease was investigated. Cross-sectional analysis within a prospective cohort study. The Canadian Alliance for Healthy Hearts and Minds Cohort Study; a pan-Canadian cohort of cohorts. Canadian adults (n = 6645) recruited between 2014-2018 from the provinces of British Columbia, Alberta, Ontario, Quebec, and Nova Scotia, were studied, for whom averages of exposures to nitrogen dioxide (NO2), ozone (O3), and fine particulate matter (PM2.5) were estimated for the years 2008-2012. Carotid vessel wall volume (CWV) measured by magnetic resonance imaging (MRI). In adjusted linear mixed models, PM2.5 was not consistently associated with CWV (per 5 μg/m3 PM2.5; adjusted estimate = -8.4 mm3; 95% Confidence Intervals (CI) -23.3 to 6.48; p = 0.27). A 5 ppb higher NO2 concentration was associated with 11.8 mm3 lower CWV (95% CI -16.2 to -7.31; p<0.0001). A 3 ppb increase in O3 was associated with 9.34 mm3 higher CWV (95% CI 4.75 to 13.92; p<0.0001). However, the coarse/insufficient O3 resolution (10 km) is a limitation. In a cohort of healthy Canadian adults there was no consistent association between PM2.5 or NO2 and increased CWV as a measure of subclinical atherosclerosis by MRI. The reasons for these inconsistent associations warrant further study.

Large vessel vasculitis evaluation by CTA: impact of deep-learning reconstruction and “dark blood” technique

ObjectivesTo assess the performance of the “dark blood” (DB) technique, deep-learning reconstruction (DLR), and their combination on aortic images for large-vessel vasculitis (LVV) patients.Materials and methodsFifty patients diagnosed with LVV scheduled for aortic computed tomography angiography (CTA) were prospectively recruited in a single center. Arterial and delayed-phase images of the aorta were reconstructed using the hybrid iterative reconstruction (HIR) and DLR algorithms. HIR or DLR DB image sets were generated using corresponding arterial and delayed-phase image sets based on a “contrast-enhancement-boost” technique. Quantitative parameters of aortic wall image quality were evaluated.ResultsCompared to the arterial phase image sets, decreased image noise and increased signal-noise-ratio (SNR) and CNRouter (all p < 0.05) were obtained for the DB image sets. Compared with delayed-phase image sets, dark-blood image sets combined with the DLR algorithm revealed equivalent noise (p > 0.99) and increased SNR (p < 0.001), CNRouter (p = 0.006), and CNRinner (p < 0.001). For overall image quality, the scores of DB image sets were significantly higher than those of delayed-phase image sets (all p < 0.001). Image sets obtained using the DLR algorithm received significantly better qualitative scores (all p < 0.05) in all three phases. The image quality improvement caused by the DLR algorithm was most prominent for the DB phase image sets.ConclusionDB CTA improves image quality and provides better visualization of the aorta for the LVV aorta vessel wall. The DB technique reconstructed by the DLR algorithm achieved the best overall performance compared with the other image sequences.Critical relevance statementDeep-learning-based “dark blood” images improve vessel wall image wall quality and boundary visualization.Key PointsDark blood CTA improves image quality and provides better aortic wall visualization.Deep-learning CTA presented higher quality and subjective scores compared to HIR.Combination of dark blood and deep-learning reconstruction obtained the best overall performance.Graphical

Drug eluting stents trigger the secretion of inflammatory proteins in an experimental in vitro study

Abstract Introduction Ischemic cardiovascular diseases commonly appear following the occlusion of one or more of the coronary arteries. Drug eluting stents (DES) constitute the gold standard to help to keep open the arteries and maintain the blood flow. After their placement into the coronary arteries, they stay in direct contact with the blood stream, disturbing the physiological conditions and interacting with several cells and proteins within the surrounding blood and vessel wall. Besides the beneficial effects of DES, their clinical application is also associated with complications, such as (late) stent thromboses. Previous studies have shown that thrombosis and inflammation are tightly linked with each other by activating inflammatory cells and secreting cytokines and chemokines to further promote an inflammatory surrounding. However, the influence of DES and their components on the inflammatory cascade and their corresponding players was not investigated yet. Methods To investigate the inflammatory secretome in response to DES, we performed an in vitro study with isolated human peripheral blood mononuclear cells (PBMCs). Therefore, PBMCs were isolated from the whole blood of four healthy volunteers. In total, 63 stents were used in the study, including Medtronic Resolute Onyx (n=37), Abbott XIENCE Sierra (n=5), Boston Scientific SYNERGY (n=4), Terumo Ultimaster (n=3), and Biotronik Orsiro (n=14). We measured the secretion of cytokines and chemokines, including IL-1β, IL-6, TNF-α, IL-8, and IL-12, as well as ICAM-1, VCAM-1, and MCP-1 by commercially available enzyme-linked immunosorbent assay (ELISA). Results Our results showed that DES significantly increase the secretion of the cytokines IL-1β (p=0.0005), and IL-6 (p=0.0002), as well as the chemokine IL-8 (p=0.0010). Additionally, we also detected an elevation of the reaction product ICAM-1 (p=0.0003). Further analyses resulted in a reduced secretion of IL-1β, IL-6, TNF-α, IL-8, and ICAM-1 into the cells’ supernatants in response to Resolute Onyx stents, in comparison to the other stents. Moreover, multiple regression analysis revealed a high dependency of the inflammatory reaction on the elution drug, the polymer type and the stent’s length. Additionally, the material of the stent platform, as well as the polymer thickness further have impact on the cytokine and chemokine response of PBMCs. Conclusion Our study indicate that DES by themselves trigger an inflammatory reaction of blood cells by the secretion of cytokines and chemokines. Furthermore, we provided first insights into the composition of the inflammosome in response to DES. A triggered inflammation may increase the vulnerability for complications and the failure of the DES. As these complications were already observed in clinical studies, our results would potentially provide predictions about the application of certain DES designs and may help to choose the appropriate stents in the clinical setting.

Apolipoprotein B and the regression of lipidic plaque in statin-treated type 2 DM patients with coronary artery disease: the pre-specified sub-analysis from the OPTIMAL randomized controlled trial

Abstract Introduction Type 2 diabetic mellitus (T2DM) patients more likely present vulnerable form of diseases. Despite lowering LDL-C level with a statin, their on-going cardiovascular risks still exist, which indicates the need to identify additional therapeutic targets in T2DM patients. Apolipoprotein B (ApoB) is a proatherogenic lipoprotein. Atherosclerosis is promoted via the influx of ApoB into vessel wall. The current ESC guideline recommends ApoB levels as a secondary therapeutic target under control of LDL-C levels with a statin. However, it remains to be fully determined about the association of ApoB levels with plaque vulnerability in statin-treated T2DM patients. Purpose To elucidate whether serial change in ApoB levels affects the degree of atheroma progression and lipidic plaque materials on NIRS/IVUS imaging. Methods The OPTIMAL randomized controlled trial compared the efficacy of continuous glucose monitoring guided versus HbA1c-guided glycemic control on coronary atherosclerosis in 94 statin-treated T2DM patients with CAD. Serial NIRS/IVUS imaging was conducted at baseline and week 48 to monitor non-culprit lesions. The current study included 71 patients with serial ApoB levels at both baseline and week 48. Clinical demographics and NIRS/IVUS-derived measures were compared in those with and without any reduction of ApoB levels. Results All of study subjects received a statin, and over 60% of them were treated with high-intensity statin. Under these lipid-lowering therapies, 60.6% of study subjects exhibited any reduction of ApoB levels, accompanied by a greater reduction of LDL-C levels. Patients with any reduction of ApoB levels were more likely to be older (67.4±10.0 vs. 71.7±7.3 years, p=0.03), whereas there were no significant differences in the proportion of established risk factors between the two groups. Baseline NIRS/IVUS-derived PAV (47.1±12.9 vs. 44.8±15.4%, p=0.54) and maxLCBI4mm [290.5 (205.5, 338.7) vs. 270.0 (97.0, 416.0), p=0.76] were comparable in patients with and without any reduction of ApoB. On serial NIRS/IVUS imaging analysis, the progression rate of atheroma volume did not differ between the two groups (-0.4±0.2 vs. -0.3±0.2mm3, p=0.77). However, patients with any reduction of ApoB more frequently presented a regression of maxLCBI4mm (27.6±0.1 vs. 61.5±0.1%, p=0.01). Multivariate analysis adjusting age, female and high-intensity statin use demonstrated change in ApoB as an independent factor associated with regression of maxLCBI4mm (OR=0.94, 95%CI=0.91-0.98, p=0.002). Conclusion In statin-treated T2DM patients with CAD, any reduction of ApoB levels was associated with a greater regression of NIRS-derived maxLCBI4mm. The current findings indicate a potential anti-atherosclerotic effect of lowering ApoB levels, which induces delipidation of diabetic coronary atheroma. ApoB may be an important therapeutic target to modulate lipidic plaque materials in T2DM patients receiving a statin.

Which is better for predicting and discriminating cardiovascular events: a traditional risk score, a calcium score or a genetic risk score?

Abstract Background The most effective approach to prevent coronary artery disease (CAD) in the general population remains to quantify the individual risk of CAD followed by controlling risk factors. There has been a lot of curiosity to investigate several scores individually for improving risk prediction. However, whether one would be better than the other in the same population is still unclear. Aim To evaluate the performance of the three individual scores, European SCORE2, Coronary artery calcium score (CACS) and a Genetic risk score (GRS), in predicting and discriminating cardiovascular (CV) events in an asymptomatic Portuguese population. Methods Prospective, observational population-based study, including 1002 asymptomatic subjects (mean age 53.1±6.8 years, 73.8% male) selected from a normal Portuguese population, without apparent CAD and diabetes at baseline. Data were recorded at the end of an extended follow-up (average 6.5±4.9 years). The European SCORE2, a computed tomography CACS, and a GRS were created to evaluate CV events’ predictive and discriminative ability through Receiver Operating Characteristics (ROC) analysis and Harrell’s C-statistics. Results ROC curve analysis showed 0.723 for SCORE2, 0.815 for CACS and 0.649 for GRS. Harrell’s C-statistics were 0.731 in the SCORE2, 0.785 for CACS and 0.684 for GRS. Conclusion The CAC score was the best individual score to predict and discriminate CV events in our asymptomatic population. Its capacity to identify high-risk individuals and those asymptomatic with subclinical atherosclerosis may improve CV risk management strategies to prevent future cardiovascular events. This result can be explained because CAC score, more than a risk marker, represents the existence of disease in the vessel wall.

Conditional over-expression of heme-oxygenase 1 in myelomonocytic cells reduces AngII-induced hypertension and vascular inflammation in mice

Abstract Background Systemic arterial Hypertension is one of the most important risk factor responsible for morbidity and mortality world-wide. Angiotensin II (Ang II), a potent vasoconstrictor and key player in the renin-angiotensin-aldosterone system (RAAS) is responsible for vascular dysfunction, inflammation, and tissue damage. Heme oxygenase-1 (HO-1) overexpression may confer antioxidant and anti-inflammatory properties in Ang II-induced hypertension through its action on heme catabolism, generating carbon monoxide (CO), ferritin and biliverdin/bilirubin by the action of biliverdin reductase A (BLVRA). Methods and results Male 9–12-weeks-old HO-1indxLySMCre/wt and LySMCre/wt mice were infused with AngII (1mgAngII/Day/Kg) for 7 days to induce hypertension and compared to sham treatment. Blood pressure monitoring by tail-cuff method, and endothelium-dependent vasodilator studies via organ chamber system using acetylcholine (ACh) in isolated aortic segments (~4 mm), revealed that overexpression of HO-1 in myeloid cells resulted in decreased systolic blood pressure and improved endothelial function in AngII-infused HO-1indxLySMCre/wt mice compared to controls. Concurrently, increased BLVRA expression in liver tissue and elevated plasma bilirubin levels were detected by transcriptome analysis and high-performance liquid chromatography, respectively. These results were supported by a reduction in the expression of inducible cytokines and cell adhesion molecules (CAMs) in the aorta, assessed using qPCR. Bone marrow transplant experiments demonstrated that bone marrow from LysMcre mice in HO-1indxLySMCre/wt mice abrogated the protective effect of HO-1, resulting in endothelial damage and increased blood pressure, potentially due to decreased liver BLVRA expression and the accumulation of bone marrow-derived cells in the vessel wall in response to AngII. Additionally, adeno-associated viral vector (AAV) transfection targeting specifically BLVRA activity in liver lead to an increase in blood pressure values and worse endothelium relaxation, in parallel with higher oxidative stress and the blood neutrophils concentration, as assessed in whole blood by using oxidative burst method and blood count system respectively. Conclusion The overexpression of HO-1 in myeloid cells confers anti-inflammatory protection in AngII-induced arterial hypertension in mice. Myeloid cells bone marrow-derived overexpressing HO-1 regulate the differentiation and infiltration of pro-inflammatory immune cells in the vasculature. BLVRA expression and bilirubin levels downstream of HO-1 play a critical role in protecting against vascular damage by reducing leukocyte infiltration.

Colchicine as a therapeutic option for the treatment of pulmonary arterial hypertension (PAH) in a rat model

Abstract Introduction Pulmonary arterial hypertension (PAH) is a cardiovascular disease that is characterized by severe structural and functional damages, resulting from the obstructive remodeling of the pulmonary vasculature and consequent right ventricular pressure overload. The current therapy mainly focuses on the pulmonary vascular system, with uncertain efficacy. Therefore, it is crucial to explore new therapeutic approaches. The mechanism of colchicine is complex and not-fully understood, but it has been proven to exert cardiopulmonary protective effects. Methods PAH induction was carried out in 8-week-old male WKY rats with a single subcutaneous injection of 60 mg/kg monocrotaline. Monocrotaline, a pyrrolizidine alkaloid, is metabolized in liver and induces inflammatory processes, which can cause PAH in rats. Starting from day 14 after MCT injection, the animals received three times a week intraperitoneal colchicine treatment at a dose of 0.5 mg/kg for two weeks. Echocardiographic examinations were performed during the study. At the end of the study, besides histological examination of the right ventricles and lungs [arterial wall thickness (WT%) and area (WA%)], the expression and phosphorylation levels of the proteins involved in cardiac remodeling were evaluated using Western blot. We assessed the pyruvate dehydrogenase (PDH) enzyme activity in the heart, which plays an important role in energy metabolism. We also examined the production of cytokines and chemokines in the right ventricle. Results The VW/BW ratio in the colchicine-treated group was significantly reduced compared to the MCT group (p&amp;lt;0.01). Echocardiographic parameters, EF% and E/e' ratio – characterizing the left ventricular function – did not differ considerably between the groups during the treatment. The TAPSE and PAT values characterizing right ventricular function improved in the MCT+C group (p&amp;lt;0.05). Collagen deposition and TGFβ level were significantly reduced by colchicine (p&amp;lt;0.05) in PAH animals. In the MCT+C group, the vascular remodeling (WT% and WA%) significantly decreased compared to the MCT group (p&amp;lt;0.01). The expression of α-SMA in vessel walls was most pronounced in the MCT group (p&amp;lt;0.01), which was significantly reduced by colchicine treatment. The phosphorylation of prosurvival signaling factors (ERK1/2, Akt1, GSK3β) was significantly increased in the MCT+C group (p&amp;lt;0.01) compared to the MCT group. In the right ventricle, PDH enzyme activity increased in the MCT+C group compared to the MCT group (p&amp;lt;0.01). According to cytokine array, cytokines involved in mediating fibrosis and inflammatory processes (TIMP-1, VEGF, L-selectin, CXCL7) showed increased secretion in the MCT group, which was moderately attenuated by colchicine treatment. Conclusion Colchicine treatment reduced the extent of fibrosis and inflammation, improved the structure of the pulmonary vasculature, and enhanced right ventricular function and energy supply.

Association of vasospastic angina with myocardial bridging and pericoronary adipose tissue attenuation on computed tomography angiography

Abstract Background Recent studies have suggested that vasospastic angina (VSA) is associated with myocardial bridging (MB). The relationship between VSA and pericoronary adipose tissue (PCAT) inflammation has also been reported but still remains to be determined. Purpose We investigated clinical and coronary computed tomography angiographic (CCTA) features in patients with VSA diagnosed by spasm provocation test (SPT). Methods We retrospectively studied patients with clinically suspected VSA who underwent both SPT with intracoronary acetylcholine administration and CCTA within three months before SPT at Tsuchiura Kyodo General Hospital. PCAT inflammation was evaluated on CCTA images by fat attenuation index (FAI) which has been recently used as a novel biomarker of coronary inflammation. In FAI analysis, we measured FAI of the proximal segments not only for 4mm (FAI4mm) but also for the inner and thinner 2mm pericoronary adipose tissue layer from the vessel wall (FAI2mm), since FAI2mm has been reported to provide better discriminating efficacy for VSA diagnosis than FAI4mm. We also evaluated the presence or absence of MB and its features including length, depth and location on CCTA images. Results A total of 172 patients were studied and VSA was diagnosed in 39.0% (67/172) of patients by SPT according to the latest guideline. Male (74.6% vs 49.5%, P=0.001), smoking history (74.6% vs 48.6%, P=0.001) were more frequent, and prevalence of CCTA-defined MB (47.8% vs 34.3%, P=0.082) and RCA-FAI2mm (-68.73 HU vs -73.35 HU, P&amp;lt;0.001) were higher in patients with versus without VSA. In multivariable analysis, presence of CCTA-defined MB (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.26-5.19, P=0.0095), RCA-FAI2mm (OR 1.05, 95% CI 1.01-1.09, P=0.025), and smoking (OR 3.40, 95% CI 1.57-7.36, P=0.0019) were independently associated with VSA. A combination of high RCA-FAI2mm (≥-68.93HU, the best cut-off obtained by ROC analysis with AUC of 0.64, 95% CI 0.551 - 0.728), smoking history and existence of MB could predict VSA with 73.7% of probability, while an absence of all 3 covariates could exclude VSA with 85.3% of probability. Conclusion CCTA-defined MB, high RCA-FAI2mm and smoking were independently predictive of VSA.