Distribution Of Atherosclerotic Plaques Research Articles

Abstract 2070: Myeloid Smyd2 Deficiency Exacerbates Atherosclerosis Via Promoting Plaque Necrosis And Calcification

Introduction: The accumulation of lipoprotein-laden macrophages within arterial walls marks the earliest phase of atherosclerotic cardiovascular disease, giving rise to foam cells. Here, we aim to define the previously unexplored role of myeloid specific SMYD2 (a histone lysine methyltransferase) in atherosclerosis and plaque formation. Methods: Myeloid-specific Smyd2 knockout mice in ApoE -/- background (Smyd2 mKO ApoE -/- ) and their littermate controls (Smyd2 fl/fl ApoE -/- ) were subjected to Western diet (WD) feeding for up to 26 weeks. Atherosclerotic plaque distribution was examined by en-face Oil Red O (ORO) staining of freshly collected aortas. Hematoxylin & Eosin (H&E) staining on brachiocephalic artery (BCA) tissues were performed to determine total plaque size, lipid pool area, and necrotic core area. Plaque calcification was determined by von Kossa staining and Alizarin Red S staining. Primary bone marrow derived macrophages (BMDMs) isolated from Smyd2 fl/fl ApoE -/- and Smyd2 mKO ApoE -/- mice and cultured RAW 246.7 cells (with Smyd2 knock-down) were used for in vitro studies including calcification assay, PR-PCR, and Western blot analysis. Results: Myeloid Smyd2 deficient mice demonstrated significantly increased aortic plaque burden on ORO staining as compared to control mice following WD feeding, though with slower WD-induced body weight gain relative to Smyd2 fl/fl ApoE -/- control mice. H&E staining of BCA indicated that there was significant reduction in total lumen and lipid core area, while significantly increased total plaque and necrotic core in Smyd2 mKO ApoE -/- mice. Myeloid Smyd2 deletion promotes plaque calcification in mice fed with WD, and in cultured BMDMs and RAW 246.7 cells treated with calcification promoting media. Gene expression analysis of key calcification factors of aortic tissues and cultured cells showed significant upregulation of Sox9 and Msx2 genes in aortas of WD-fed Smyd2 mKO ApoE -/- mice and cultured Smyd2 deficient cells, as compared to controls. Conclusion: We delineated the consequences of Smyd2 deficiency in macrophages on atherosclerotic plaque development, particularly its impact on plaque necrosis and calcification.

Abstract P3022: Smyd2 Deficiency Protects Against Atherosclerotic Plaque Formation Through Modulation Of Oxidative Stress

Introduction: Oxidative stress induced vascular remodeling promotes atherosclerosis. By scavenging excessive ROS levels, NRF2 protects vascular cells against oxidative stress and exerts anti-inflammatory activity through modulation of HO-1. This study aimed to explore smooth muscle cell (SMC)-specific role of SMYD2 in modulating atherosclerosis associated oxidative stress in vivo and in vitro . Methods: SMC-specific SMYD2 knockout mice in ApoE -/- background (SMYD2 ΔSMC ApoE -/- ) and their littermate controls (SMYD2 fl/fl ApoE -/- ) were subjected to Western diet feeding for 18-26 weeks. Atherosclerotic plaque distribution was examined by en-face Oil Red O (ORO) staining of aortas from both groups. Hematoxylin & Eosin (H&E) staining on brachiocephalic artery tissues were performed to determine atherosclerotic plaque burden by measurements of total plaque size, lipid pool area, and necrotic core area. Lipid peroxidation was analyzed in aortic tissues and in blood serum. Primary VSMCs isolated from control and SMYD2 depleted mice and cultured C3H/ 10T1 / 2 cells were used for in vitro studies. Results: SMC-specific SMYD2 depletion attenuated atherosclerotic plaque establishment and progression. En -face ORO analysis revealed significant suppression of ORO positive areas in SMYD2 ΔSMC ApoE -/- mice compared to control mice. H&E analysis of lesions showed significant reduction of total plaque size, despite accumulation of lipids, in SMYD2 ΔSMC ApoE -/- mice as compared to control mice. Immunofluorescence staining of aortic tissues showed increased expression of NRF2, HO-1 and GPX4 in SMYD2 ΔSMC ApoE -/- mice compared to controls, as observed in serum by MDA assay. Mechanistic studies using C3H/ 10T1 / 2 cells treated with PAz-PC (oxLDL), GPX4 inhibitor, with or without SMYD2 knockout, demonstrated that SMYD2 modulates HO-1 and GPX4 expression through NRF2. Specifically, SMYD2 binds NRF2 and reduces its translocation into the nucleus, thereby repressing HO-1 expression and inducing oxidative stress. Conclusion: SMYD2 depletion induces atheroprotective effect via reducing plaque burden and promoting antioxidant activity of NRF2/HO-1 axis, suggesting SMYD2 could be a therapeutic target against atherosclerosis.

The cell origins of foam cell and lipid metabolism regulated by mechanical stress in atherosclerosis.

Atherosclerosis is an inflammatory disease initiated by endothelial activation, in which lipoprotein, cholesterol, extracellular matrix, and various types of immune and non-immune cells are accumulated and formed into plaques on the arterial wall suffering from disturbed flow, characterized by low and oscillating shear stress. Foam cells are a major cellular component in atherosclerotic plaques, which play an indispensable role in the occurrence, development and rupture of atherosclerotic plaques. It was previously believed that foam cells were derived from macrophages or smooth muscle cells, but recent studies have suggested that there are other sources of foam cells. Many studies have found that the distribution of atherosclerotic plaques is not random but distributed at the bend and bifurcation of the arterial tree. The development and rupture of atherosclerotic plaque are affected by mechanical stress. In this review, we reviewed the advances in foam cell formation in atherosclerosis and the regulation of atherosclerotic plaque and lipid metabolism by mechanical forces. These findings provide new clues for investigating the mechanisms of atherosclerotic plaque formation and progression.

HR-MRI findings of intracranial artery stenosis and distribution of atherosclerotic plaques caused by different etiologies.

To investigate the etiology of intracranial artery stenosis and the distribution characteristics of intracranial artery atherosclerotic stenosis using high-resolution magnetic resonance imaging (HR-MRI). A total of 262 patients with intracranial artery stenosis that underwent HR-MRI from November 2019 to December 2020 were retrospectively enrolled. The etiology of intracranial anterior and posterior circulation artery stenosis was analyzed, and the relationship between the location of plaques and the distribution characteristics of plaques and the occurrence of ischemic stroke was summarized. A total of 276 plaques were identified with HR-MRI. There were 101 cases (36.59%) in the middle cerebral artery (MCA), 14 cases (5.07%) in the posterior cerebral artery (PCA), 90 cases (32.62%) in vertebral artery (VA), and 71 cases (25.72%) in the basilar artery (BA). The infarct rate of ventral and superior wall MCA plaques was higher than that of dorsal and inferior wall (63.33% vs 31.25% P = 0.021) (100.00% vs 50% P = 0.022). MCA with plaques throughout the course had the greatest degree of stenosis (P < 0.001). Sphenoid segment (M1) of MCA was most susceptible (85 cases, 84.16%), MCA plaques were most common in the proximal M1 segment (35 cases, 34.65%), and most BA plaques were found in the distal segment (28 cases, 39.44%). PCA plaques were most frequently involved in traffic anterior segment (P1) (7 cases, 50.00%). HR-MRI could provide accurate imaging reference for clinical evaluation of intracranial arterial stenosis and formulation of treatment plans. The intracranial arterial plates mostly appeared in the middle cerebral artery and vertebral artery. Middle cerebral arteries with atherosclerotic plaques are more likely to narrow.

Influence of myocardial bridge on atherosclerotic plaque distribution and characteristics evaluated by near-infrared spectroscopy intravascular ultrasound

This study aims to clarify whether myocardial bridge (MB) could influence atherosclerotic plaque characteristics assessed using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) imaging. One hundred and sixteen patients who underwent percutaneous coronary intervention (PCI) using NIRS-IVUS imaging were included. MB was defined as an echo-lucent band surrounding left anterior descending artery (LAD). In MB patients, LAD was divided into three segments: proximal, MB, and distal segments. In non-MB patients, corresponding three segments were defined based on the average length of the above segments. Segmental maximum plaque burden and lipid content derived from NIRS-IVUS imaging in the section of maximum plaque burden were evaluated in each segment. Lipid content of atherosclerotic plaque was evaluated as lipid core burden index (LCBI) and maxLCBI4mm. LCBI is the fraction of pixels indicating lipid within a region multiplied by 1000, and the maximum LCBI in any 4-mm region was defined as maxLCBI4mm. MB was identified in 42 patients. MB was not associated with maximum plaque burden in proximal segment. LCBI and maxLCBI4mm were significantly lower in patients with MB than those without in proximal segment. Multivariable analysis demonstrated both MB and maximum plaque burden in proximal segment to be independent predictors of LCBI in proximal segment. Lipid content of atherosclerotic plaque assessed by NIRS-IVUS imaging was significantly smaller in patients with MB than those without. MB could be considered as a predictor of lipid content of atherosclerotic plaque when assessed by NIRS-IVUS imaging.

Abstract 11412: Methyltransferase Smyd2 Mediate Atherosclerotic Plaque Calcification

Introduction: Clinical manifestation of atherosclerosis is marked by calcification of vasculature, including the expression of mineralization regulating proteins (Sox9, Msx2, and Runx2) by vascular smooth muscle cells (VSMCs). This pathogenic remodeling of VSMCs into osteochondrogenic cell types is accompanied by increased proliferation, migration, and secretion of extracellular matrix proteins. This study aimed to determine the spatiotemporal role of SMYD2 in atherosclerotic plaque progression and calcification. Methods: SMC-specific SMYD2 knockout was generated in ApoE -/- mice (SMYD2 ΔSMC ApoE -/- ). Age and body weight-matched mice were fed with Western diet (WD) for 18 or 26 weeks. The distribution of atherosclerotic plaque was examined by En-face Oil-Red-O staining (ORO) of freshly collected aorta. Atherosclerotic plaque burden was determined by Hematoxylin &amp; Eosin (H&amp;E) staining. Collagen content and calcification of atherosclerotic plaque were determined by Masson's trichrome staining and von Kossa staining, respectively. The calcification-regulatory genes (MGP1, AGG and transcription factors SOX9, MSX2, BMP2, and RUNX2) in the aorta were analyzed by RT-qPCR. Results: SMC-specific deletion of SMYD2 protected mice from atherosclerotic plaque calcification. En-face ORO and H&amp;E analysis of Brachiocephalic artery demonstrated a significant decrease in ORO positive area, total plaque size, and necrotic core area in SMYD2 ΔSMC ApoE -/- mice as compared to ApoE-/- mice, with no change in the distribution of collagen fibers. Von Kossa staining showed hydroxyapatite depots at the medial lining of the vasculature (microcalcification) in ApoE -/- mice fed with 18-week Western diet, while a smaller depot of macrocalcification was observed in SMYD2 ΔSMC ApoE -/- mice compared with ApoE -/- mice when fed with 26-week WD. mRNA analysis of key calcification transcription factors showed significant suppression of SOX9 and MSX2 genes in aortas of SMYD2 ΔSMC ApoE -/- mice compared with ApoE -/- mice, with downward trends of BMP2 and RUNX2 in both 18- or 26-week WD. Conclusion: SMYD2 ablation attenuates atherosclerotic plaque formation and calcification, suggests targeting SMYD2 can be a potential therapeutic strategy for atherosclerosis.

Myocardial bridge analysis by multidetector computed tomography and its association with coronary atherosclerosis

Abstract Background Myocardial Bridging an inborn coronary abnormality, is defined as a segment of a major epicardial coronary artery, the tunneled artery, that goes intramurally through the myocardium beneath the muscle bridge. Objective To evaluate noninvasively the presence and distribution of atherosclerotic plaques in relation to myocardial bridge coronary segments and to determine the prevalence of myocardial bridges and their location and morphology by using MDCT. Patients and Methods The study population consisted of 55 patients presented with chest pain, referred for MDCT coronary angiography and found to have myocardial bridge at during the period from April 2018 and August 2019. 23 patients was found having Myocardial Bridge and coronary artery atherosclerotic plaques included in Group (A), 29 persons found having Myocardial Bridge without CAD included in Group (B). All patients were subjected to detailed history taking, clinical evaluation, ECG analysis and MSCT coronary angiography. Results In the present study, patients with atherosclerotic plaque (group A) (n = 29), mean age was 52.41 ± 10.55 years ranged from 35.0 to 73.0 years, 41.4% were males, while in Myocardial bridge without atherosclerotic lesion group (group B) (n = 26), mean age was 51.65 ± 7.58 ranged from 38.0 to 65.0 years., 30.8% were males. Conclusion Our study showed that diabetes mellitus and dyslipidemia are a significant risk factor for developing atherosclerotic plaque in the segment proximal to myocardial bridge. Myocardial bridge were usually located over the Mid segment of the left anterior descending coronary artery

Mitochondrial Dysfunction in Vascular Wall Cells and Its Role in Atherosclerosis.

Altered mitochondrial function is currently recognized as an important factor in atherosclerosis initiation and progression. Mitochondrial dysfunction can be caused by mitochondrial DNA (mtDNA) mutations, which can be inherited or spontaneously acquired in various organs and tissues, having more or less profound effects depending on the tissue energy status. Arterial wall cells are among the most vulnerable to mitochondrial dysfunction due to their barrier and metabolic functions. In atherosclerosis, mitochondria cause alteration of cellular metabolism and respiration and are known to produce excessive amounts of reactive oxygen species (ROS) resulting in oxidative stress. These processes are involved in vascular disease and chronic inflammation associated with atherosclerosis. Currently, the list of known mtDNA mutations associated with human pathologies is growing, and many of the identified mtDNA variants are being tested as disease markers. Alleviation of oxidative stress and inflammation appears to be promising for atherosclerosis treatment. In this review, we discuss the role of mitochondrial dysfunction in atherosclerosis development, focusing on the key cell types of the arterial wall involved in the pathological processes. Accumulation of mtDNA mutations in isolated arterial wall cells, such as endothelial cells, may contribute to the development of local inflammatory process that helps explaining the focal distribution of atherosclerotic plaques on the arterial wall surface. We also discuss antioxidant and anti-inflammatory approaches that can potentially reduce the impact of mitochondrial dysfunction.

Progression from normal vessel wall to atherosclerotic plaque: lessons from an optical coherence tomography study with follow-up of over 5years.

The initial process of atherosclerotic development has not been systematically evaluated. This study aimed to observe atherosclerotic progression from normal vessel wall (NVW) to atherosclerotic plaque and examine local factors associated with such progression using > 5-year long-term follow-up data obtained by serial optical coherence tomography (OCT). A total of 49 patients who underwent serial OCT for lesions with NVW over 5years (average: 6.9years) were enrolled. NVW was defined as a vessel wall with an OCT-detectable three-layer structure and intimal thickness ≤ 300μm. Baseline and follow-up OCT images were matched, and OCT cross sections with NVW > 30° were enrolled. Cross sections were diagnosed as "progression" when the NVW in these cross sections was reduced by > 30° at > 5-year follow-up. Atherogenic progression from NVW to atherosclerotic plaque was observed in 40.8% of enrolled cross sections. The incidence of microchannels in an adjacent atherosclerotic plaque within the same cross section(6.7 vs. 3.3%; p = 0.046) and eccentric distribution of atherosclerotic plaque (25.0 vs. 12.6%; p < 0.001) at baseline was significantly higher in cross sections with progression than in those without. Cross sections with progression exhibited significantly higher NVW intimal thickness at baseline than cross sections without progression (200.1 ± 53.7 vs. 180.2 ± 59.6μm; p < 0.001). Multivariate analysis revealed that the presence of microchannels in an adjacent atherosclerotic plaque, eccentric distribution of atherosclerotic plaque, and greater NVW intimal thickness at baseline were independently associated with progression at follow-up. The presence of microchannels in an adjacent atherosclerotic plaque, eccentric distribution of atherosclerotic plaque, and greater NVW intimal thickness were potentially associated with initial atherosclerotic development from NVW to atherosclerotic plaque.

Correlation of coronary artery geometry with the complexity and severity of coronary atherosclerosis: rationale and design of the GEOMETRY-CTA study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This research is co-financed by Greece and the European Union (European Social Fund-ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning 2014-2020» in the context of the project “Correlation of coronary artery tree geometry and clinical parameters with the distribution, complexity and severity of coronary artery disease: a pilot study using multislice CT coronary angiography” (MIS 5047882) Background Development and progression of coronary atherosclerosis is complex and not yet fully understood. Accumulative evidence supports the notion that coronary artery disease (CAD) results from an interaction of systemic factors, such as dyslipidemia, with local hemodynamic factors that regulate the site-specific predilection of atherosclerosis, particularly low endothelial shear stress (ESS). Since low ESS develops in geometrically irregular regions of the coronary tree for a given arterial blood flow, geometrical factors affect atherosclerotic plaque distribution and vulnerability. However, the correlation of coronary geometric features with the complexity and severity of CAD has not been fully elucidated. Purpose GEOMETRY-CTA is a prospective, non-randomized, observational study that aims to investigate the correlation of coronary artery geometrical features with the complexity and severity of CAD using Coronary Computed Tomography Angiography (CCTA). The prognostic value of a CCTA-derived geometric risk score will also be assessed. Methods The study aims to recruit 100 consecutive patients with suspected CAD and low/intermediate pre-test probability. Coronary geometrical characteristics such as angulation of coronary bifurcations, tortuosity, coronary artery volume index (CAVi) and vessel-length will be assessed with multi-planar reformation and volume rendering techniques, and integrated into a single geometric risk score. The extent and vulnerability of plaque burden will be calculated using several anatomical scoring systems such as the Leiden CTA risk score, CT-SYNTAX score, and CT-adapted Gensini score. Patients will be prospectively followed for 12 months after enrollment. Results The primary objective of the study is to evaluate the correlation of the geometric risk score with CAD severity and plaque vulnerability. We also hypothesize that wider bifurcation angles and lower CAVi augmenting the atherosclerosis-prone environment and predict higher CAD extent and complexity. Conclusion The present study aims to introduce a quantitative, non-invasive imaging biomarker expressing CAD severity and investigate its prognostic value in regards to adverse cardiovascular events. The derived index will be available for incorporation in larger national prospective studies for further cardiovascular risk stratification.

Harmine alleviates atherogenesis by inhibiting disturbed flow-mediated endothelial activation via protein tyrosine phosphatase PTPN14 and YAP.

Disturbed flow induces endothelial dysfunction and contributes to uneven distribution of atherosclerotic plaque. Emerging evidence suggests that harmine, a natural constituent of extracts of Peganum harmala, has potent beneficial activities. Here, we investigated if harmine has an atheroprotective role under disturbed flow and the underlying mechanism. Mice of ApoE-/- , LDLR-/- , and endothelial cell (EC)-specific overexpression of yes-associated protein (YAP) in ApoE-/- background were fed with a Western diet and given harmine for 4 weeks. Atherosclerotic lesion size, cellular composition, and expression of inflammatory genes in the aortic roots were assessed. HUVECs were treated with oscillatory shear stress (OSS) and harmine and also used for proteomic analysis. Harmine retarded atherogenesis in both ApoE-/- and LDLR-/- mice by inhibiting the endothelial inflammatory response. Mechanistically, harmine blocked OSS-induced YAP nuclear translocation and EC activation by reducing phosphorylation of YAP at Y357. Overexpression of endothelial YAP blunted the beneficial effects of harmine in mice. Proteomic study revealed that protein tyrosine phosphatase non-receptor type 14 (PTPN14) could bind to YAP. Moreover, harmine increased PTPN14 expression by stabilizing its protein level and inhibiting its degradation in proteasomes. PTPN14 knockdown blocked the effects of harmine on YAPY357 and EC activation. Finally, overexpression of PTPN14 mimicked the effects of harmine and ameliorated atherosclerosis, and knockdown of PTPN14 blunted the atheroprotective effects of harmine and accelerated atherosclerosis, in a partial ligation mouse model. Harmine alleviated OSS-induced EC activation via a PTPN14/YAPY357 pathway and had a potent atheroprotective role.

Deep learning reveals 3D atherosclerotic plaque distribution and composition

Complications of atherosclerosis are the leading cause of morbidity and mortality worldwide. Various genetically modified mouse models are used to investigate disease trajectory with classical histology, currently the preferred methodology to elucidate plaque composition. Here, we show the strength of light-sheet fluorescence microscopy combined with deep learning image analysis for characterising and quantifying plaque burden and composition in whole aorta specimens. 3D imaging is a non-destructive method that requires minimal ex vivo handling and can be up-scaled to large sample sizes. Combined with deep learning, atherosclerotic plaque in mice can be identified without any ex vivo staining due to the autofluorescent nature of the tissue. The aorta and its branches can subsequently be segmented to determine how anatomical position affects plaque composition and progression. Here, we find the highest plaque accumulation in the aortic arch and brachiocephalic artery. Simultaneously, aortas can be stained for markers of interest (for example the pan immune cell marker CD45) and quantified. In ApoE−/− mice we observe that levels of CD45 reach a plateau after which increases in plaque volume no longer correlate to immune cell infiltration. All underlying code is made publicly available to ease adaption of the method.

Abstract 14949: Influence of Myocardial Bridge on Atherosclerotic Plaque Distribution and Characteristics Evaluated by Near Infrared Spectroscopy

Introduction: Myocardial bridge (MB) has been reported to be associated with developed atherosclerosis in the segment proximal to MB. Near-Infrared Spectroscopy (NIRS) identify the lipid content of atherosclerotic plaque as lipid core burden index (LCBI) but little is known about the influence of MB on characteristics of atherosclerosis assessed by NIRS imaging. Methods: 116 consecutive patients who underwent percutaneous coronary intervention using NIRS were included. MB was defined as an echo-lucent band surrounding left anterior descending artery (LAD) which could be detected by gray-scale intravascular ultrasound (IVUS). In MB patients, LAD was divided into 3 segments: proximal segment, MB segment, and distal segment. In non-MB patients, corresponding 3 segments were defined based on the average length of the above segments. Segmental maximum plaque burden and lipid content derived from NIRS-IVUS imaging in the section of maximum plaque burden were evaluated in each segment. Results: MB was identified in 42 patients. MB was not associated with maximum plaque burden in the proximal segment. Whereas MB was negatively correlated with both LCBI and max LCBI 4mm in the proximal segment. Multivariable analysis demonstrated both MB and maximum plaque burden in proximal segment to be independent predictors of LCBI or LCBI 4mm in proximal segment. Conclusions: MB was negatively correlated with both LCBI and max LCBI 4mm in the proximal segment and could be considered as an independent predictor of lipid content of atherosclerotic plaque assessed by NIRS-IVUS imaging.

Glomus-saving carotid endarterectomy by A. N. Kazantsev. Hospital and medium-remote results

Aim. Analysis of the results of hospital and medium-long-term results obtained using a new method of glomus-saving carotid endarterectomy (CEE) according to A. N. Kazantsev.Methods. This prospective study was conducted during January 2018 to April 2020 on 214 patients who were operated for occlusive stenotic lesions of the internal carotid artery (ICA) using holomus-saving CEE as per the method described by A.N. Kazantsev. The average observation duration was 17.2 ± 6.5 months. Glomus-saving CEE as per the method by A. N. Kazantsev is performed as follows. Arteriotomy is performed along the inner edge of the external carotid artery (ECA) adjacent to the carotid sinus, 2–3 cm above the mouth, depending on the distribution of atherosclerotic plaque, with a transition to the common carotid artery (also 2–3 cm below the ECA mouth). The ICA was cut off at the site formed by the wall sections of the ECA and the common carotid artery. Thereafter, an endarterectomy from the ICA was performed using the eversion technique. The next step was an open endarterectomy from the ECA and OCA. Then, the ICA at the saved site was implanted in the previous position. A 6-0 Prolene thread was used as the suture material for performing a vascular anastomosis.Results. The average ICA clamping time was 33.1 ± 3.4 min. Considering the intraoperative visualisation of an extended atherosclerotic plaque in the ICA, in some cases, there was a need to transform the operation. In 4.7% (n = 10) cases, autologous ICA transplantation was performed as per E. V. Rosseykinu. During the hospitalisation, the observation of cardiovascular complications was not recorded. When analysing the dynamics graph of systolic blood pressure, it was revealed that after glomus-saving CEE as per the method by A. N. Kazantsev, stable numbers are maintained during preoperative antihypertensive therapy and do not rise above 137.9 ± 7.5 mm Hg. In the mid-long-term follow-up, 1 (0.46 %) death was recorded, 1 (0.46%) due to myocardial infarction, 1 (0.46%) due to non-lethal ischaemic stroke, and 2 (0.9%) due to hemodynamically significant restenosis 12 mon after CEE. The combined endpoint (death + myocardial infarction + stroke) was reached in 3 (1.4%) patients. The cause of the lethal outcome was circular myocardial infarction that developed, given the patient's refusal to follow double disaggregant therapy (2 stents were previously implanted in the anterior descending and right coronary arteries). The cause of ischaemic stroke was the development of ICA restenosis (12 mon after CEE) owing to neointimal hyperplasia, as shown by histological examination after repeated surgery.Conclusion. CEE as per the method by A. N. Kazantsev is the simplest method of operation for known glomus-preserving reconstructions. The absence of complex arteriotomy, the preservation of carotid bifurcation structures, and the possibility of transformation of the intervention into autologous autologous transplantation with prolonged lesion is preferred over other methods. An additional opportunity for high-quality endarterectomy from ЕCA also creates preventive conditions in the prevention of cerebral haemodynamics. Stable blood pressure indicators in the hospital and mid-term follow-up periods demonstrate the importance of the preservation of the carotid glomus during reconstructive surgery on the carotid arteries. Thus, the presented type of CEE meets all the requirements of modern carotid surgery and can be an elective operation in the personalised treatment of patients with occlusal-stenotic lesions of the carotid arteries. Received 10 May 2020. Revised 25 May 2020. Accepted 26 May 2020. Funding: The study did not have sponsorship. Conflict of interest: Authors declare no conflict of interest. Author contributionsMethod development and testing: A.N. KazantsevConception and design: T.E. Zaitseva, A.E. Chikin, A.N. KazantsevDrafting the article: A.N. KazantsevDrawing up tables: E.Yu. KalininStatistical analysis: K.P. ChernykhLiterature review: R.Yu. Leader, G.Sh. BagdavadzeCritical revision of the article: N.E. Zarkua, K.G. KubachevFinal approval of the version to be published: A.N. Kazantsev, K.P. Chernykh, R.Yu. Leader, N.E. Zarkua, K.G. Kubachev, G.Sh. Bagdavadze, E.Yu. Kalinin, T.E. Zaitseva, A.E. Chikin, Yu.P. Linets

Intravascular Photoacoustic and Autofluorescence Imaging for Detecting Intraplaque Hemorrhage: A Feasibility Study

Intraplaque hemorrhage (IPH), which is a trigger and conveys all blood components into the plaque, influencing the cholesterol crystal formation and retention, haemoglobin and oxidative enzymes, and blood-borne proteolytic activity. IPH is one of the key determinants for plaque vulnerability. In this paper, we proposed a dual-modality endoscope probe with a diameter of 1 mm for simultaneously detecting the lipid core and IPH, our system was composed of photoacoustic imaging (PAI) and near-infrared auto-fluorescence imaging (NIRAFI). The lipid as endogenous marker of intravascular PAI could visualize the lipid distribution of atherosclerotic plaque, and bilirubin as the marker of intravascular NIRAFI was used to locate and quantify the IPH. The phantom and ex vivo rabbit aorta experiments had proved the feasibility and capability of the dual-mode probe for imaging IPH and lipid core expansion. And the results indicated that the dual-mode intravascular endoscope had the potential for accurately detecting IPH in atherosclerotic plaques.

Abstract 17183: Genetically Engineered Calcification Increases Surface Roughness and Changes the Distribution of Atherosclerotic Plaques in Mice With Atherosclerosis

Background: Atherosclerosis is an inflammatory disease that contributes significantly to cardiovascular mortality. Arterial stiffening due to calcification can coexist with or directly influence pathogenesis of atherosclerosis. We hypothesize that arteriosclerosis caused by genetically engineered calcification in mice redistributes shear stress on the endothelial cells, which in turn leads to further accelerated rate of plaque formation. Methods: All of the mice had an LDL receptor mutation and were fed pro-atherogenic diet (1.25% cholesterol). The case group overexpressed tissue-nonspecific alkaline phosphatase in endothelial cells (eTNAP). The luminal surfaces of descending thoracic aorta (TA) and suprarenal abdominal aorta (AA) were scanned using Sensofar S Neox optical confocal microscope at 1 μm vertical resolution. The surface topographies per sample, each measuring 500 x 700 microns, were analyzed for ISO 25178-2 areal roughness parameters using SensoMap. Parameters were compared by t test (n=5 eTNAP, n=6-7 control). Results: We observed a significant difference in the incidence as well as the morphology of the plaques in the eTNAP group compared to control mice. There was a 4.8 fold increase in the number of topological motifs in the thoracic aorta of the eTNAP vs. controls (p &lt; 0.01). Similarly, the number of motifs was increase in the abdominal aorta of the eTNAP mice compared to controls (2.8 fold; p=0.06). The average area of the motifs was significantly larger in the controls compared to the eTNAP group in both segments of the aorta (p=0.06 TA; p &lt; 0.05 AA). The maximum height of the lesions in the TA was not different between the groups (p=0.62), however increased by 74% in the abdominal aorta of the eTNAP compared to controls (p&lt;0.05). Finally, the surface developed interfacial area ratio (Sdr, a parameter of texture) was increased in the eTNAP group in both the TA (p &lt; 0.05) and AA regions (p &lt; 0.01). Conclusion: Arteriosclerosis increases surface roughness. In our model, the abdominal region had a high incidence of taller, irregular lesions whereas those in the thoracic aorta were flatter and more spaced. The high resolution scans will be further used to study the hemodynamic disturbances to the endothelial cells using flow dynamics simulations.

Plaque distribution in common femoral artery bifurcations, based on multi-slice computed tomography assessment.

The aim of this study was to observe the exact plaque distribution at the common femoral artery bifurcation by multi-slice computed tomography angiography and to examine the relationship between plaque distribution and carina location. Symptomatic outpatients who underwent multi-slice computed tomography angiography between May 2013 and February 2015 were enrolled in this study. The presence and distribution of atherosclerotic plaques were assessed in cross section views of vessel lumen. Each vessel lumen cross section was divided into four equal quadrants for the common femoral, superficial femoral and profunda femoral arteries. The quadrant of the superficial femoral artery in which the carina was located was also recorded. In total, 184 common femoral artery bifurcations in 92 patients were analyzed. Normal arteries were more common in profunda femoral arteries than in common femoral arteries and superficial femoral arteries (both P< 0.001). Plaques were found more medial and posterior quadrants in common femoral arteries. In superficial femoral arteries, plaques were found most frequently in anterior quadrants (78.3%, n=144) and least frequently in posterior quadrants (49.5%, n=91). The carina was located in the posterior quadrant in 160 bifurcations (87.0%) of superficial femoral arteries. Quadrants opposite the carina contained plaque most proportionally (77.2%) and quadrants of carina were affected least proportionally (52.7%) in superficial femoral arteries (P.

Evaluation of basilar artery atherosclerotic plaque distribution by 3D MR vessel wall imaging.

Basilar artery (BA) atherosclerosis is an important cause of perforator stroke in the brainstem due to plaque involvement of the perforator ostia in BA dorsal or lateral walls. Therefore, to acquire information on plaque distribution is important to better understand and prevent the perforator stroke. This study aimed to comprehensively evaluate BA plaque distribution with 3D magnetic resonance imaging (MRI) vessel wall imaging. Consecutive patients with cerebrovascular symptoms and stenosis or irregular luminal surface of BA were recruited and underwent BA 3D proton density-weighted volume isotropic turbo spin echo acquisition (VISTA) imaging at 3T. The cross-sectional and longitudinal distribution of BA plaque were analyzed with a custom-developed tool. In all, 85 BA plaques were detected in 61 recruited patients. For cross-sectional distribution, the prevalence of plaque involvement in the ventral, left, dorsal, and right quadrant of BA wall was 74.1%, 70.6%, 67.1%, and 62.4%, respectively. Of the 85 plaques, 17.7% involved one quadrant and 82.3% involved two or more quadrants. The most severe plaque region was more commonly situated at lateral walls (66.1%) as compared to ventral (23.2%, P < 0.001) and dorsal walls (10.6%, P < 0.001). Longitudinally, plaques were more frequently found to occur at BA segment distal than proximal to anterior inferior cerebellar artery (AICA) (63.5% vs. 36.5%). Taking advantage of 3D MR vessel wall imaging, BA plaques were found to more likely affect lateral walls and form in BA distal to AICA, where most perforators originate, suggesting that it might be useful to characterize BA plaque distribution before aggressive treatment for prevention of perforator stroke. J. Magn. Reson. Imaging 2016;44:1592-1599.

Coronary computed tomography angiography based assessment of endothelial shear stress and its association with atherosclerotic plaque distribution in-vivo.

PurposeThe relationship between low endothelial shear stress (ESS) and coronary atherosclerosis is well established. ESS assessment so far depended on invasive procedures. The aim of this study was to demonstrate the relationship between ESS and coronary atherosclerosis by using non-invasive coronary computed tomography angiography (CTA) for computational fluid dynamics (CFD) simulations.MethodsA total number of 7 consecutive patients with suspected coronary artery disease who received CTA and invasive angiography with IVUS analysis were included in this study. CTA examinations were performed using a dual-source scanner. These datasets were used to build a 3D mesh model. CFD calculations were performed using a validated CFD solver. The presence of plaque was assumed if the thickness of the intima-media complex exceeded 0.3 mm in IVUS. Plaque composition was derived by IVUS radiofrequency data analysis.ResultsPlaque was present in 32.1% of all analyzed cross-sections. Plaque prevalence was highest in areas of low ESS (49.6%) and high ESS (34.8%). In parts exposed to intermediate-low and intermediate-high ESS few plaques were found (20.0% and 24.0%) (p<0.001). Wall thickness was closely associated with local ESS. Intima-media thickness was 0.43±0.34mm in low and 0.38±0.32mm in high ESS segments. It was significantly lower when the arterial wall was exposed to intermediate ESS (0.25±0.18mm and 0.28 ± 0.20mm) (p<0.001). Fibrofatty tissue was predominately found in areas exposed to low ESS (p≤0.023).ConclusionsIn this study a close association of atherosclerotic plaque distribution and ESS pattern could be demonstrated in-vivo. Adding CFD analysis to coronary CTA offers the possibility to gather morphologic and physiologic data within one non-invasive examination.

The role of septal perforators and "myocardial bridging effect" in atherosclerotic plaque distribution in the coronary artery disease.

SummaryThe distribution of atherosclerotic plaque burden in the human coronary arteries is not uniform. Plaques are located mostly in the left anterior descending artery (LAD), then in the right coronary artery (RCA), circumflex branch (LCx) and the left main coronary artery (LM) in a decreasing order of frequency. In the LAD and LCx, plaques tend to cluster within the proximal segment, while in the RCA their distribution is more uniform. Several factors have been involved in this phenomenon, particularly flow patterns in the left and right coronary artery. Nevertheless, it does not explain the difference in lesion frequency between the LAD and the LCx as these are both parts of the left coronary artery. Branching points are considered to be the risk points of atherosclerosis. In the LCx, the number of side branches is lower than in the LAD or RCA and there are no septal perforators with intramuscular courses like in the proximal third of the LAD and the posterior descending artery (PDA). We hypothesized that septal branches generate disturbed flow in the LAD and PDA in a similar fashion to the myocardial bridge (myocardial bridging effect). This coronary architecture determines the non-uniform plaque distribution in coronary arteries and LAD predisposition to plaque formation.