Intimal Plaque Research Articles

Morin, a matrix metalloproteinase 9 inhibitor, attenuates endothelial-to-mesenchymal transition in atherosclerosis by downregulating Notch-1 signaling

ObjectiveAtherosclerotic cardiovascular disease poses a significant health challenge globally. Recent findings highlight the pivotal role of the endothelial-to-mesenchymal transition (EndMT) in atherosclerosis. Morin is a bioflavonoid mainly extracted from white mulberry, a traditional Chinese herbal medicine with anti-inflammatory and antioxidant properties. This study examines whether morin can alleviate atherosclerosis by suppressing EndMT and seeks to elucidate the underlying mechanism. MethodsWe induced an in vitro EndMT model in human umbilical vein endothelial cells (HUVECs) by stimulating the cells with transforming growth factor β1 (TGF-β1) (10 ng/mL) for 48 h. The in vivo experiments were performed in an atherosclerosis model using apolipoprotein E (ApoE)–/– mice fed with a high-fat diet (HFD). Mice in the intervention group were given morin (50 mg/kg) orally for 4 weeks. Molecular docking and microscale thermophoresis were assayed to understand the interactions between morin and matrix metalloproteinase 9 (MMP-9). ResultsMorin inhibited the expression of EndMT markers in a dose-dependent manner in TGF-β1-treated HUVECs. Administering 50 μmol/L morin suppressed the upregulation of MMP-9 and Notch-1 signaling in TGF-β1-induced EndMT. Moreover, the overexpression of MMP-9 activated Notch-1 signaling, thereby reversing morin’s inhibitory effect on EndMT. In the HFD-induced atherosclerotic ApoE–/– mice, morin notably reduced aortic intimal hyperplasia and plaque formation by suppressing EndMT. Furthermore, morin demonstrated a strong binding affinity for MMP-9. ConclusionMorin acts as an MMP-9 inhibitor to disrupt EndMT in atherosclerosis by limiting the activation of Notch-1 signaling. This study underscores morin’s potential utility in the development of anti-atherosclerotic medication.

Three-Dimensional Imaging of Aortic Tissues in Atherosclerosis.

Recent research has advanced the understanding of atherosclerosis as a transmural chronic inflammatory disease involving all three layers of the arterial wall, including the intima plaque, the media, and the adventitia, which forms the outer connective tissue coat of arteries. Our recent studies have suggested that the adventitia is used by the peripheral nervous system as a conduit for reaching all tissue cells. We also found that the peripheral nervous system, that is, the sensory and sympathetic nervous system, undergoes major remodeling processes involving the neogenesis of axon networks adjacent to atherosclerotic plaques. In this context, understanding the structure of the neural network and its interactions with vascular components of diseased arteries holds major promises for a better understanding of cardiovascular disease pathogenesis. To achieve these objectives, methods to visualize the subcellular architecture of the intact healthy and diseased arteries together with their surrounding perivascular compartments are needed. Tissue clearing allows intact deep-tissue imaging of larger tissue compartments that are otherwise inaccessible. It allows volumetric imaging of intact arteries through the integration of labeling, clearing, advanced microscopic imaging, and image processing tools. Here, we describe two distinct but complementary passive tissue clearing approaches, that is, aqueous-based 2, 2-thiodiethanol (TDE) clearing and solvent-based immunolabeling-enabled three-dimensional imaging of solvent-cleared organ (iDISCO) clearing to image isolated aortic segments or whole aorta in-situ in the whole mouse.

Site-specific m6A-miR-494-3p, not unmethylated miR-494-3p, compromises blood brain barrier by targeting tight junction protein 1 in intracranial atherosclerosis.

Intracranial atherosclerosis is one of the most common causes of ischaemic stroke. However, there is a substantial knowledge gap on the development of intracranial atherosclerosis. Intracranial arteries are characterized by an upregulation of tight junctions between endothelial cells, which control endothelial permeability. We investigated the role of N6-methyladenosine (m6A), a common RNA modification, on endothelial integrity, focusing on the pro-atherogenic microRNA miR-494-3p and tight junction proteins TJP1 and PECAM1. We assessed the m6A landscape, along with the expression of miR-494-3p, TJP1 and PECAM1 in postmortem human vertebral arteries (VA), internal carotid arteries (ICA), and middle cerebral arteries (MCA) with various stages of intimal thickening and plaque formation. The interactions between m6A-modified miR-494-3p mimics, TJP1 and PECAM1, were investigated in vitro using primary human (brain) endothelial cells. Increased m6A expression was observed in the luminal lining of atherosclerosis-affected VAs, accompanied by reduced TJP1 and PECAM1, but not VE-cadherin, expression. Colocalization of m6A and miR-494-3p in the luminal lining of VA plaques was confirmed, indicating m6A methylation of miR-494-3p in intracranial atherosclerosis. Moreover, site-specific m6A-modification of miR-494-3p led to repression specifically of TJP1 protein expression at cell-cell junctions of brain microvascular endothelial cells, while unmodified miR-494-3p showed no effect. This study highlights increasing m6A levels during intracranial atherogenesis. Increases in m6A-miR-494-3p contribute to the observed decreased TJP1 expression in endothelial cell-cell junctions. This is likely to have a negative effect on endothelial integrity and may thus accelerate intracranial atherosclerosis progression.

Reactive Oxygen Species-Responsive Nanoparticle Delivery of Small Interfering Ribonucleic Acid Targeting Olfactory Receptor 2 for Atherosclerosis Theranostics.

Atherosclerosis (AS) is a chronic inflammatory disorder characterized by arterial intimal lipid plaques. Small interfering ribonucleic acid (siRNA)-based therapies, with their ability to suppress specific genes with high targeting precision and minimal side effects, have shown great potential for AS treatment. However, targets of siRNA therapies based on macrophages for AS treatment are still limited. Olfactory receptor 2 (Olfr2), a potential target for plaque formation, was discovered recently. Herein, anti-Olfr2 siRNA (si-Olfr2) targeting macrophages was designed, and the theranostic platform encapsulating si-Olfr2 to target macrophages within atherosclerotic lesions was also developed, with the aim of downregulating Olfr2, as well as diagnosing AS through photoacoustic imaging (PAI) in the second near-infrared (NIR-II) window with high resolution. By utilization of a reactive oxygen species (ROS)-responsive nanocarrier system, the expression of Olfr2 on macrophages within atherosclerotic plaques was effectively downregulated, leading to the inhibition of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and interleukin-1 β (IL-1β) secretion, thereby reducing the formation of atherosclerotic plaques. As manifested by decreased Olfr2 expression, the lesions exhibited a significantly alleviated inflammatory response that led to reduced lipid deposition, macrophage apoptosis, and a noticeable decrease in the necrotic areas. This study provides a proof of concept for evaluating the theranostic nanoplatform to specifically deliver si-Olfr2 to lesional macrophages for AS diagnosis and treatment.

Mechanisms of Medial Wall Thinning in Chronic Total Occlusion

BackgroundThe success rate of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is lower and the risk for complications higher compared with other non-CTO PCI. Although interventionalists focus on intimal plaque characteristics, the coronary media is an important (especially for techniques involving antegrade dissection and re-entry) but poorly understood structure in CTO PCI. ObjectivesThe aim of the present study was to investigate coronary medial wall thinning in CTO lesions and determine how this thinning might affect CTO PCI. MethodsA total of 2,586 sections were investigated, from arteries with evidence of CTO from 54 subjects (1,383 sections) and arteries without evidence of CTO from 54 subjects with non-coronary-related deaths (1,203 sections) after matching for age, gender, body weight, and body height. ResultsThe medial thickness in subjects with CTO was lower than that in those with non-coronary-related death (P < 0.001). In subjects with CTO, CTO lesions had thinner medial walls compared with those with lower luminal narrowing (P < 0.001). At the CTO distal segments, the 6- to 12-mm distal segment from the distal end of the CTO had significantly less luminal narrowing (P < 0.001), and similar medial thickness, compared with the distal end of the CTO. Immunohistochemical analysis revealed that short-duration CTO had more cleaved caspase-3–positive cells in media and had significantly more CD3+, CD4+, CD8+, and CD4+CD28null T cells compared with long-duration CTO. ConclusionsCTO lesions demonstrated coronary medial thinning compared with non-CTO lesions. Further investigation of the cause-and-effect relationship among inflammation, apoptosis, and coronary medial wall thinning is warranted in future mechanistic studies.

Rendezvous-PIERCE technique: establishing a channel through severe calcification in infrainguinal arterial lesions using needle rendezvous

BackgroundSevere calcification often prevents device passage and balloon expansion in cases of lower extremity artery disease. To address this limitation, we introduced a novel calcium modification technique called Rendezvous-PIERCE (R-PIERCE).MethodsA needle was inserted in a retrograde manner and advanced to touch the tip of an antegrade guidewire within the lesion. Then, the guidewire was advanced into the lumen of the needle to achieve partial guidewire externalization, also known as needle rendezvous. The needle was then introduced over the externalized guidewire under wire tension and repeatedly rotated and advanced across the lesion to modify calcified intimal plaques. Notably, this technique can be applied in the opposite direction.ResultsCase 1 involved a 68-year-old male with a calcified occlusion of the anterior tibial artery. An antegrade guidewire reached the midpoint of the occlusion; however, microcatheters and balloons could not pass through the proximal calcification. Therefore, R-PIERCE was used to modify uncrossable lesions. An antegrade 2.5-mm balloon crossed and dilated the lesion, achieving hemostasis at the needle insertion site. The antegrade guidewire successfully crossed the entire lesion and was dilated by the 2.5-mm balloon. Final angiography demonstrated successful flow. In Case 2, an 80-year-old male had a calcified femoropopliteal occlusion. An antegrade guidewire was advanced into the distal superficial femoral artery (SFA); however, no device could follow it. R-PIERCE was performed to modify the calcification from the distal to the medial SFA. The antegrade balloon successfully crossed and dilated obstructed lesions. Furthermore, the antegrade guidewire crossed the entire lesion, and the antegrade balloon was dilated. Final angiography revealed a successful flow without complications.ConclusionsR-PIERCE is useful for modifying complex calcified lesions during the wiring of occlusive lesions.

Computed tomographic angiography measures of coronary plaque in clinical trials: opportunities and considerations to accelerate drug translation.

Atherosclerotic coronary artery disease (CAD) is the causal pathological process driving most major adverse cardiovascular events (MACE) worldwide. The complex development of atherosclerosis manifests as intimal plaque which occurs in the presence or absence of traditional risk factors. There are numerous effective medications for modifying CAD but new pharmacologic therapies require increasingly large and expensive cardiovascular outcome trials to assess their potential impact on MACE and to obtain regulatory approval. For many disease areas, nearly a half of drugs are approved by the U.S. Food & Drug Administration based on beneficial effects on surrogate endpoints. For cardiovascular disease, only low-density lipoprotein cholesterol and blood pressure are approved as surrogates for cardiovascular disease. Valid surrogates of CAD are urgently needed to facilitate robust evaluation of novel, beneficial treatments and inspire investment. Fortunately, advances in non-invasive imaging offer new opportunity for accelerating CAD drug development. Coronary computed tomography angiography (CCTA) is the most advanced candidate, with the ability to measure accurately and reproducibly characterize the underlying causal disease itself. Indeed, favourable changes in plaque burden have been shown to be associated with improved outcomes, and CCTA may have a unique role as an effective surrogate endpoint for therapies that are designed to improve CAD outcomes. CCTA also has the potential to de-risk clinical endpoint-based trials both financially and by enrichment of participants at higher likelihood of MACE. Furthermore, total non-calcified, and high-risk plaque volume, and their change over time, provide a causally linked measure of coronary artery disease which is inextricably linked to MACE, and represents a robust surrogate imaging biomarker with potential to be endorsed by regulatory authorities. Global consensus on specific imaging endpoints and protocols for optimal clinical trial design is essential as we work towards a rigorous, sustainable and staged pathway for new CAD therapies.

Essential oil from Fructus Alpinia zerumbet ameliorates atherosclerosis by activating PPARγ-LXRα-ABCA1/G1 signaling pathway

BackgroundAtherosclerosis (AS) is a progressive chronic disease. Currently, cardiovascular diseases (CVDs) caused by AS is responsible for the global increased mortality. Yanshanjiang as miao herb in Guizhou of China is the dried and ripe fruit of Fructus Alpinia zerumbet. Accumulated evidences have confirmed that Yanshanjiang could ameliorate CVDs, including AS. Nevertheless, its effect and mechanism on AS are still largely unknown. PurposeTo investigate the role of essential oil from Fructus Alpinia zerumbet (EOFAZ) on AS, and the potential mechanism. MethodsA high-fat diet (HFD) ApoE−/− mice model of AS and a oxLDL-induced model of macrophage-derived foam cells (MFCs) were reproduced to investigate the pharmacological properties of EOFAZ on AS in vivo and foam cell formation in vitro, respectively. The underlying mechanisms of EOFAZ were investigated using Network pharmacology and molecular docking. EOFAZ effect on PPARγ protein stability was measured using a cellular thermal shift assay (CETSA). Pharmacological agonists and inhibitors and gene interventions were employed for clarifying EOFAZ's potential mechanism. ResultsEOFAZ attenuated AS progression in HFD ApoE−/− mice. This attenuation was manifested by the reduced aortic intima plaque development, increased collagen content in aortic plaques, notable improvement in lipid profiles, and decreased levels of inflammatory factors. Moreover, EOFAZ inhibited the formation of MFCs by enhancing cholesterol efflux through activiting the PPARγ-LXRα-ABCA1/G1 pathway. Interestingly, the pharmacological knockdown of PPARγ impaired the beneficial effects of EOFAZ on MFCs. Additionally, our results indicated that EOFAZ reduced the ubiquitination degradation of PPARγ, and the chemical composition of EOFAZ directly bound to the PPARγ protein, thereby increasing its stability. Finally, PPARγ knockdown mitigated the protective effects of EOFAZ on AS in HFD ApoE−/− mice. ConclusionThese findings represent the first confirmation of EOFAZ's in vivo anti-atherosclerotic effects in ApoE−/− mice. Mechanistically, its chemical constituents can directly bind to PPARγ protein, enhancing its stability, while reducing PPARγ ubiquitination degradation, thereby inhibiting foam cell formation via activation of the PPARγ-LXRα-ABCA1/G1 pathway. Simultaneously, EOFAZ could ameliorates blood lipid metabolism and inflammatory microenvironment, thus synergistically exerting its anti-atherosclerotic effects.

Increased 12/15-lipoxygenase by disturbed flow promotes endothelial dysfunction and the development of atherosclerosis

Abstract Introduction Atherosclerosis is predisposed at bifurcations, branch points and arterial curvatures where the blood flow is disturbed. Deposition and oxidative modification of low-density lipoprotein (LDL) in the subendothelial intima is an early event in the pathogenesis of atherosclerosis. However, the effect of disturbed flow (d-flow) on LDL oxidation and the underlying mechanisms remain unclear. Purpose In this study, we investigated the role of 12/15-lipoxygenase (LOX) in LDL oxidation in endothelial cells (EC) and the development of atherosclerosis at d-flow sites. Methods En face immunofluorescence was performed to analyze the expression of 12/15-LOX in EC under exposure to different flow patterns. Protein expression and LDL oxidation was studied in vitro by using 2 different flow apparatuses. Animal model of d-flow was established by partial ligation of the carotid artery. Results En face staining exhibited a significant increase in 12/15-LOX protein expression in EC in areas exposed to d-flow than those exposed to steady flow (s-flow). Carotid partial ligation in ApoE knockout mice led to substantially increased deposition of oxidized LDL in the subendothelial intima and formation of atherosclerotic plaques in the carotid artery, whereas these detrimental effects by d-flow were markedly attenuated in ApoE/12/15-LOX double knockout mice. In cultured EC, d-flow generated by a reversal flow pump markedly promoted the expression of 12/15-LOX and translocation of the protein onto the cell membrane. Inhibition of 12/15-LOX in EC, either by knockdown with its specific siRNA or a pharmacological inhibitor, suppressed production of 15s-HETE and LDL oxidation in response to d-flow. Mechanically, we found d-flow induced the expression of 12/15-LOX by activating a specific responsive element in the 12/15-LOX promoter through recruiting a shear stress-sensitive transcriptional factor SREBP2. Chromatin immunoprecipitation further confirmed the interaction of SREBP2 with the promoter of 12/15-LOX upon d-flow exposure. Conclusions These data define an essential role of 12/15-LOX in promoting the pathogenesis of atherosclerosis under d-flow by increasing LDL oxidation in EC through SREBP2 signaling.

Clonal Proliferation Within Smooth Muscle Cells in Unstable Human Atherosclerotic Lesions.

Studies in humans and mice using the expression of an X-linked gene or lineage tracing, respectively, have suggested that clones of smooth muscle cells (SMCs) exist in human atherosclerotic lesions but are limited by either spatial resolution or translatability of the model. Phenotypic clonality can be detected by X-chromosome inactivation patterns. We investigated whether clones of SMCs exist in unstable human atheroma using RNA in situ hybridization (BaseScope) to identify a naturally occurring 24-nucleotide deletion in the 3'UTR of the X-linked BGN (biglycan) gene, a proteoglycan highly expressed by SMCs. BGN-specific BaseScope probes were designed to target the wild-type or deletion mRNA. Three different coronary artery plaque types (erosion, rupture, and adaptive intimal thickening) were selected from heterozygous females for the deletion BGN. Hybridization of target RNA-specific probes was used to visualize the spatial distribution of mutants. A clonality index was calculated from the percentage of each probe in each region of interest. Spatial transcriptomics were used to identify differentially expressed transcripts within clonal and nonclonal regions. Less than one-half of regions of interest in the intimal plaque were considered clonal with the mean percent regions of interest with clonality higher in the intimal plaque than in the media. This was consistent for all plaque types. The relationship of the dominant clone in the intimal plaque and media showed significant concordance. In comparison with the nonclonal lesions, the regions with SMC clonality had lower expression of genes encoding cell growth suppressors such as CD74, SERF-2 (small EDRK-rich factor 2), CTSB (cathepsin B), and HLA-DPA1 (major histocompatibility complex, class II, DP alpha 1), among others. Our novel approach to examine clonality suggests atherosclerosis is primarily a disease of polyclonally and to a lesser extent clonally expanded SMCs and may have implications for the development of antiatherosclerotic therapies.

Shenlian extract improves atherosclerosis by relieving adventitial inflammation

Ethnopharmacological relevanceShenlian (SL) extract, a Chinese medicinal compound mainly pointing at inflammation response of atherosclerosis, is composed of Salvia miltiorrhizae Bunge and Andrographis paniculata (Burm.f.) Nees. Salvia miltiorrhizae Bunge has been reported to activate blood to remove stasis, while another herb, Andrographis paniculata (Burm.f.) Nees, has been revealed to clear endogenous heat toxins. The anti-atherosclerotic effects of these two herbs have been reported closely relating to inflammation. However, from the point of view of adventitial inflammation, the in-depth study of SL extract in anti-atherosclerotic effects by relieving adventitial inflammation is still unknown. Aim of the studyTo explore the effects of adventitial inflammation in atherosclerosis progression and if SL extract could reverse the process. Materials and methodsA novel atherosclerosis model based on adventitial inflammation was established. High-fat diet-fed ApoE-/- mice were implanted a cotton thread soaked with LPS on the right common carotid artery (RCCA). Meanwhile, three time points were set (week 2, 4, and 12) to accurately evaluate the effect of SL extract on the whole process of atherosclerosis with adventitial inflammation. The pathological changes of phenotype transformation of VAFs, vascular cell proliferation and collagen synthesis were observed dynamically by immunohistochemistry (IHC), BrdU method and sirius red staining. Then primary VAFs were stimulated by LPS to mirror the process of adventitial inflammation in vitro. The VAFS phenotype conversion and its function alterations including proliferation, migration, inflammatory secretion was assessed. Finally, we established a co-culture model of activated VAFs and vascular smooth muscle cells (VSMCs) to observe the impacts of activated VAFs on phenotype transformation and migration of VSMCs. ResultsSL extract improved atherosclerosis progression by reducing lipid content, adventitial inflammation and plaque formation. HE results showed sham-operated group (Sham) appeared light infiltrated inflammation only in adventitia at week 2, and the degree of inflammation infiltrated in model was more severe than that in Sham at week 2, 4, and 12. At week 12, the sham and model group showed evidently thickened media and intima. The phenotypic transformation, proliferation and migration of vascular adventitial fibroblasts (VAFs) as well as inflammatory secretion enhanced remarkably in vivo and vitro, but SL extract reversed these changes. Moreover, SL extract downregulated JAK2-STAT3-MMP2 signal pathway. The VSMCs transformed from contractile phenotype into synthetic phenotype and the migration of VSMCs increased after co-culture with activated VAFs. In contrast, SL extract could suppress theses effects. ConclusionsTaken together, atherosclerotic inflammation could be a “outside-in” signaling. Adventitial inflammation not only accelerated intimal plaque formation in atherosclerosis, but also worsened the degree of vascular lesion. And SL extract improved atherosclerosis by relieving adventitial inflammation, and the underlying mechanisms could be associated with curbing phenotypic transformation, proliferation and migration of VAFs and VSMCs.

Female Reproductive Events and Subclinical Atherosclerosis of the Brain and Carotid Arteriopathy: the Ohasama Study.

Few studies have investigated the subclinical atherosclerotic changes in the brain and carotid artery, and in East Asian populations. We sought to investigate whether gravidity, delivery, the age at menarche and menopause and estrogen exposure period are associated with subclinical atherosclerosis of the brain and carotid arteriopathy. This cross-sectional study formed part of a cohort study of Ohasama residents initiated in 1986. Brain atherosclerosis and carotid arteriopathy were diagnosed as white matter hyperintensity (WMH) and lacunae evident on brain magnetic resonance imaging (MRI) and carotid intimal media thickness (IMT) or plaque revealed by ultrasound, respectively. The effect of the reproductive events on brain atherosclerosis and carotid arteriopathy was investigated using logistic regression and general linear regression models after adjusting for covariates. Among 966 women aged ≥ 55 years in 1998, we identified 622 and 711 women (mean age: 69.2 and 69.7 years, respectively) who underwent either MRI or carotid ultrasound between 1992-2008 or 1993-2018, respectively. The highest quartile of gravidity (≥ 5 vs. 3) and delivery (≥ 4 vs. 2), and the highest and second highest (3 vs. 2) quartiles of delivery were associated with an increased risk of WMH and carotid artery plaque, respectively. Neither of age at menarche, menopause, and estrogen exposure period estimated by subtracting age at menarche from age at menopause was associated with atherosclerotic changes of brain and carotid arteries. Higher gravidity and delivery are associated with subclinical atherosclerosis of the brain and carotid plaque.

Monocyte Differentiation‐Surveilling Nano‐Shuttles for Activatable Targeted Inhibition of Atherosclerotic Plaque Progression

AbstractAtherosclerosis can form intimal plaques in the arteries and undergo plaque rupture with followed stroke or myocardial infarction under certain pathological conditions. However, suboptimal intraplaque accumulation, along with severe off‐target effects, remain formidable obstacles for efficient pharmacotherapy of atherosclerosis. A characteristic feature of the progression of atherosclerosis is the continuous recruitment of inflammatory monocytes that differentiate into foamy macrophages with the generation of legumain in the plaques. In this study, a bio‐activatable nano‐shuttle based on human serum albumin is conceived that contained curcumin to allow the precise inhibition of atherosclerosis progression. Following intravenous injection, the nano‐shuttles are almost exclusively engulfed by inflammatory monocytes in an efferocytosis‐mimetic manner and selectively co‐migrated with the monocytes towards the plaques. The nano‐shuttles are readily activated to release the initially arrested curcumin in response to the generation of legumain upon the differentiation of monocytes into foamy macrophages within the plaques. Treatment assessments on atheroprone apolipoprotein‐E‐deficient mice indicated that the nano‐shuttles substantially inhibit the progression of atherosclerosis by attenuating the plaque inflammation burden without any obvious adverse effects. The integration of highly selective accumulation and specific drug activation of the nano‐shuttles in plaques can arouse an advanced therapeutic strategy to prevent atherosclerotic cardiovascular disease.

Transient Perivascular Inflammation of the Carotid Artery (TIPIC) Syndrome after Breast Implant Surgery (P2-5.003)

<h3>Objective:</h3> Describe a rare case of TIPIC syndrome in a patient with breast implants. <h3>Background:</h3> TIPIC syndrome is a rare cause of neck pain caused by inflammation of unknown etiology. Silicone from the breast implant shell may may leak in the systemic circulation and trigger silicone implant incompatibility syndrome (SIIS) a form of autoimmune/inflammatory syndrome induced by adjuvants (ASIA). Several autoimmune conditions including vasculitis at distance from the implant were described. The association between breast implantation and TIPIC syndrome was not reported yet. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> 38-year-old woman with a history of asthma, HIV, and depression complained of refractory left-sided neck pain for ten days. Pain started gradually, was sharp, radiating to the left face, and was aggravated by motion and swallowing. Three weeks before onset, she had transient respiratory infection. She denied preceding neck trauma or other neurological symptoms. Acetaminophen, oxycodone, morphine and ketorolac provided moderate, short-lived relief. She had sex reassignment surgery including breast implants. Her home medications were spironolactone, estradiol, aripiprazole, emtricitabine and tenofovir disoproxil fumarate. She drinks alcohol occasionally. Clinical examination revealed left neck tenderness but no bruit, warmth, or swelling. Neurological examination was normal. CT showed eccentric hypoattenuation surrounding the left distal common carotid artery and a soft intimal plaque. MRI showed enhancement surrounding the left as well as the right common carotid artery without luminal narrowing, suggestive of TIPIC. Neck pain resolved after a short course of oral prednisone. ESR and CRP were normal. Repeated MRI after 6 months showed resolution of the perivascular inflammation. <h3>Conclusions:</h3> This is the first TIPIC case reported after breast implantation, suggesting an autoimmune response. Reactivity against the left carotid plaque is an alternative cause, but it does not explain the inflammation around the right carotid artery where is no plaque. TIPIC syndrome should be differentiated from other causes of vasculitis and dissection. <b>Disclosure:</b> Dr. Peringassery Sateesh has nothing to disclose. Dr. Marchidann has stock in Eli Lilly. Dr. Marchidann has stock in Pfizer. Dr. Marchidann has stock in Merck. Dr. Marchidann has stock in Illumina. Dr. Marchidann has stock in Aeterna Zentaris. Dr. Marchidann has stock in Abbot. Dr. Marchidann has received publishing royalties from a publication relating to health care. Dr. Marchidann has received publishing royalties from a publication relating to health care.

392 A Morphological Study of Non-Stenotic Carotid Atheromas Causing Recurrent Strokes: Chronicle of Disruption and Stabilization

INTRODUCTION: Symptomatic non-stenotic carotid (SyNC) artery disease is a recognized etiology of ischemic strokes with a putative thromboembolic mechanism. To date, the structural phenotypes expressed at the lumen/wall interface of these lesions are not completely understood resulting in misdiagnosis and hindering the development of targeted therapies. METHODS: After IRB approval, en block endarterectomy specimen were obtained from patients with recurrent strokes from SyNC (n=9). Additionally, segments of superficial temporal artery (STA) of patients undergoing cerebral artery bypass surgeries were obtained as controls (n=3). The endovascular surfaces of the samples were imaged with laser microangioscopy and scanning electron microscopy (SEM). Images were benchmarked with histological sections and immunohistochemistry (IHC). RESULTS: Normal endothelial surfaces in STA were light pink, smooth and homogenous by angioscopy with typical cobblestone endothelial pattern. Features recognized as those associated with plaque disruption and thrombosis were de-endothelialization, inflammatory infiltrates within and under the endothelium, delamination (flaps oriented to the flow) with superficial intimal hemorrhages, plaque erosion and disruption of the fibrous cap with fissuring, ulceration, excavation and plaque hemorrhage. Additionally, cellular and acellular structures actively involved in plaque stabilization, seen on SEM and confirmed with histology and IHC, were also identified including activated platelets, fibrin band, bridges and webs, neutrophil extracellular traps and endothelial progenitor cells. CONCLUSIONS: This ultrastructural study of the vascular surface of SyNC specimens reveals concurrent phenotypes of flow-dependent disruption and stabilization that could become new imaging biomarkers and enable the development of targeted therapies.

Effect of local unstable atherosclerotic plaque on plaque formation in the carotid artery and abdominal aorta of rabbits

To analyze the effect of local unstable atherosclerotic plaque on plaque formation in the carotid and aortic arteries of rabbits. Thirty New Zealand white rabbits were randomly divided into atherosclerosis model group, highfat diet feeding group, and normal chow feeding group (blank control group). In the model group, carotid artery balloon injury was induced after 4 weeks of high-fat diet feeding. Eight weeks later, all the rabbits were euthanized for histopathological examination of the carotid artery and abdominal aorta, and the mean intimal thickness and plaque to lumen area ratio were measured using image analysis software. Venous blood samples were collected from the rabbits for blood lipid analysis. At the ends of 4, 8 and 12 weeks, the rabbits in the model group and high-fat feeding group, but not those in the blank control group, all showed significant weight gain compared with their body weight at 0 week (P < 0.05). The mean intimal thickness was significantly greater in atherosclerosis model group than in the other two groups (P < 0.05). In atherosclerosis model group, the mean intimal thickness and plaque to lumen area ratio in the injured carotid artery were significantly greater than those in the contralateral carotid artery and abdominal aorta (P < 0.05). At the end of the 12 weeks, the levels of triglyceride (TG), total cholesterol (TC), low-density cholesterol (LDL-C), high-density cholesterol (HDL-C) and highsensitivity C-reactive protein (CRP) were all significantly higher in the model group and high-fat feeding group than in the blank control group (P < 0.05); the levels of TG, TC, LDL-C, or HDL-C did not differ significantly between the model group and high-fat feeding group (P>0.05), but the level of CRP was significantly higher in arteriosclerosis model group (P < 0.05). Local unstable atherosclerotic plaque can increase the level of CRP and promote the formation of atherosclerotic plaques in the carotid artery and abdominal aorta in rabbits.

VASCULAR SMOOTH MUSCLE CELL PHENOTYPIC DIFFERENTIATION AND METABOLIC DYSFUNCTION IN THORACIC AORTA ATHEROSCLEROSIS

Changes in vascular smooth muscle cells (vSMC) have proven to be a contributing factor to the development and progression of atherosclerosis. Following arterial injury, vSMCs can undergo differentiation to acquire phenotypes resembling foam cells, mesenchymal stem cells, and osteochondrogenic cells, which can all aid in intimal plaque formation and promote vascular stenosis. Dynamin-related protein 1 (Drp1) is a cytosolic GTPase that mediates mitochondrial fission. Increased mitochondrial fission is affiliated with SMC proliferation and migration, thus increasing the formation of neointimal hyperplasia, forming an anatomical basis for atherosclerosis development.

Early Diagnosis and Treatment of Coronary Heart Disease with Image Features of Optical Coherence Tomography under Adaptive Segmentation Algorithm.

This research was aimed at exploring the application value of optical coherence tomography (OCT) images under adaptive segmentation algorithm in the early diagnosis of coronary heart disease (CHD). Eighty-two patients with CHD were included, who were to undergo coronary angiography (CAG) to confirm their condition. According to the diagnostic criteria of CHD in the American Coronary Artery Surgery Study (CASS), the patients were divided into the stable plaque group (41 cases) and unstable plaque group (41 cases). Besides, 20 healthy volunteers were selected as the control group, and all of them underwent OCT scans. On the basis of a fourth-order partial differential equation (PDE) and active contour (AC) model, a novel adaptive image segmentation algorithm PDE-AC was constructed and used for OCT image processing. No significant difference was found in general clinical data and serological indicators in the control group compared to the other two groups (P > 0.05). The lipid plaque length, degree of stenosis, and lipid pool angle, macrophages and intimal erosion, and plaque fissure in the unstable plaque group were highly greater than those in the stable plaque group. The fibrous cap thickness (FCT) was significantly thinner than that in the stable plaque group (P < 0.05). The diagnostic sensitivity, specificity, and accuracy of OCT under PDE-AC algorithm for CHD (91.53%, 84.08%, and 95.38%) were markedly higher than those of single OCT (83.46%, 75.11%, and 88.02%) (P < 0.05). In summary, OCT images under PDE-AC algorithm did better than simple OCT images in the diagnosis of CHD. Lipid plaque length, degree of stenosis, and lipid pool angle, macrophage and intimal erosion, plaque fissure, and FCT were important indicators for judging plaque stability, having the better clinical application value.

Additional Acupuncture Confers a Favorable Long-Term Prognosis for Elderly Hypertensive Patients with Carotid Atherosclerosis after Atorvastatin Treatment.

Objective The purpose of the study is to investigate the clinical efficacy and long-term prognosis of acupuncture (AP) combined with atorvastatin (ATO) in treating senile essential hypertension (EH) complicated with carotid atherosclerosis (CA). Methods 108 elderly EH patients with CA admitted to our hospital between January 2018 and September 2018 were enrolled into the study, consisting of 67 patients who received treatment of AP with ATO (AP + ATO group) and 41 patients who received treatment of ATO alone (ATO group). Comparative outcomes included clinical efficacy, blood pressure (BP), the levels of blood lipids and inflammatory factors, carotid intima-media thickness (IMT), the number of unstable carotid intima plaques, the carotid plaque area, and the incidence of adverse reactions. All patients were followed up for 3 years to evaluate their quality of life and the recurrence rate of CA. Results The AP + ATO group presented a higher efficacy, a declined BP, and lower posttreatment levels of blood lipids and inflammatory factors than the ATO group (P < 0.05). Reductions were observed in IMT, number of plaques, and plaque area in both groups after treatment, with more significant improvements in the AP + ATO group (P < 0.05). No difference was observed in the incidence of adverse reactions between two groups after treatment (P > 0.05). The follow-up analysis demonstrated a higher SF-36 score and a lower recurrence rate of CA in the AP + ATO group than the ATO group (P < 0.05). Conclusion The findings suggested that, for elderly EH patients with CA, treatment of AP with ATO offers better clinical efficacy and safety, which not only can decline the BP, but also can reduce blood lipids and plaque formation, and improve quality of life.

Intravascular Lithotripsy for Optimal Angioplasty of Infrapopliteal Calcified Lesions.

Infrapopliteal arterial disease results from 2 major etiologies: medial calcification and intimal atheromatous plaque. Lesion calcification constitutes one of the most widely encountered risk factors for percutaneous transluminal angioplasty failure. Intravascular lithotripsy (IVL) creates selective fracturing of calcium deposits in the arterial wall, increasing the compliance of the target artery and facilitating angioplasty. Results regarding IVL utilization at femoropopliteal and infrapopliteal lesions have been very promising in terms of safety and efficacy. This review presents currently available data on IVL outcomes for infrapopliteal lesions and provides technical information for optimal use of IVL in these challenging lesions.