Atherosclerotic Artery Research Articles

The Place of Transaxillary Access in Transcatheter Aortic Valve Implantation (TAVI) Compared to Alternative Routes-A Systematic Review Article.

Transfemoral transcatheter aortic valve implantation (TAVI) has proven non-inferior or superior against surgical aortic valve replacement (SAVR) for patients at high, intermediate or low surgical risk. However, transfemoral access is not always feasible in patients with severely atherosclerotic or tortuous iliofemoral arteries. For these cases, alternative access techniques have been developed, such as transcarotid, transcaval, direct aortic or transaxillary access. In recent years, growing preference towards the transaxillary access has emerged. To provide a summary of data available on transaxillary TAVI and compare this approach to other alternative access techniques. A literature search was performed in PubMed by two independent reviewers. Studies reporting the outcome of at least 10 patients who underwent transaxillary TAVI, either in case series or in comparative studies, were included in this review. Articles not reporting outcomes according to the Valve Academic Research Consortium (VARC) 1-3 definitions were excluded. In total 193 records were found of which 18 were withheld for inclusion in this review. This review reports on the combined data of the 1519 patients who underwent transaxillary TAVI. Procedural success was achieved in 1203 (92.2%) of 1305 cases. Life-threatening, major, and minor bleeding occurred respectively in 4.5% (n = 50 in 1112 cases), 12.9% (n = 143 in 1112 cases) and 8.8% (n = 86 in 978 cases). Major and minor vascular complications were reported in respectively 6.6% (n = 83 in 1256 cases) and 10.0% (n = 105 in 1048 cases) of patients. 30-day mortality was 5.2% (n = 76 out of 1457 cases). At one year follow-up, the mortality rate was 1% (n = 184 out of 1082 cases). Similar 30-day and 1-year mortality is observed in studies that compare with transaxillary, transfemoral or other alternative access techniques (p 0.05). A wide application of transaxillary access as an alternative approach for TAVI has emerged. This technique has an excellent procedural success rate up to 92.0%, with low procedural complication rates. Clinical outcome of transaxillary TAVI is comparable to the other alternative TAVI approaches. However, these conclusions are solely based on observational data.

MicroRNA-98 inhibition accelerates the development of atherosclerosis via regulation of dysfunction of endothelial cell

ABSTRACT Background Atherosclerosis has been recognized as a chronic inflammation initiated by dysfunction of endothelial cell that contributes to the increased morbidity and mortality of severe cardiovascular events. The reported important role of microRNA-98 (miR-98) in regulation of endothelial cell behaviors prompt us to hypothesize that miR-98 could be involved in the process of atherosclerosis. Methods and Results The current research showed the miR-98 expression was gradually down-regulated in atherosclerotic mouse arteries isolated from ApoE ablation mice subjected to high fat diet. Additionally, a dramatically reduced miR-98 expression in endothelial cells administrated to oxidized low-density lipoprotein (Ox-LDL) but a slight down-regulated level was found in macrophages. Functionally, attenuated miR-98 expression promoted secretion of chemokines and adhesion molecules in human umbilical vein endothelial cells (HUVECs) induced by Ox-LDL, which subsequently increased infiltration and pro-inflammatory genes expression of macrophages, as well as the foam cell formation. Mechanistically, in vitro experiments indicated that the endothelial cell dysfunction regulated by miR-98 knockdown was partially contributed by upregulated expression of HMGB1. Furthermore, the animal experiment with ApoE−/− mice administrated with miR-98 inhibitor demonstrated that miR-98 silencing enhanced the atherosclerotic lesions in aorta and aortic sinus that were accompanied with increased adhesion molecules, chemokines, and pro-inflammatory markers expression. Conclusion MicroRNA-98 knockdown promoted endothelial cell dysfunction to affect the inflammatory state of macrophage and the development of atherosclerosis, at least partially, through direct targeting HMGB1. Collected, these data suggested that miR-98 could be a novel drug target for atherogenesis management.

Endothelium-Mimetic Surface Modification Improves Antithrombogenicity and Enhances Patency of Vascular Grafts in Rats and Pigs

We first identified thrombomodulin (TM) and endothelial nitric oxide (NO) synthase as key factors for the antithrombogenic function of the endothelium in human atherosclerotic carotid arteries. Then, recombinant TM and an engineered galactosidase responsible for the conversion of an exogenous NO prodrug were immobilized on the surface of the vascular grafts. Surface modification by TM and NO cooperatively enhanced the antithrombogenicity and patency of vascular grafts. Importantly, we found that the combination of TM and NO also promoted endothelialization, whereas it reduced adverse intimal hyperplasia, which is critical for the maintenance of vascular homeostasis, as confirmed in rat and pig models.

Abstract 496: Inhibition Of Tirna-gly-gcc Ameliorates Neointimal Formation Via Cbx3-mediated Vascular Smooth Muscle Cells Phenotypic Switching

Introduction: Vascular smooth muscle cells (VSMCs) are the main component of blood vessels and synthetic VSMCs play an essential role in vascular diseases. tRNA-derived fragments (tRFs) are a new class of non-coding RNAs involved in a variety of pathological processes, but their biological functions and mechanisms in VSMCs phenotype transition and vascular intimal hyperplasia are unclear. Hypothesis: We assessed the hypothesis that tRFs play important role in VSMCs phenotype transition, regulation of tRFs could ameliorates neointimal formation. Methods: Differential expression profiles of tRFs from different phenotype of VSMCs was acquired using small-RNA sequence. The expression of tiRNA-Gly-GCC was confirmed in VSMCs, vascular tissues and plasma from healthy and atherosclerosis using quantitative real-time PCR and RNA fluorescence in situ hybridization. Gain-and loss- of function were performed using mimics and inhibitors to investigate the role of tiRNA-Gly-GCC in VSMCs phenotypic transition and neointimal formation after vascular injury. Dual-luciferase reporter gene and rescue experiments were performed to demonstrate the relationship between tiRNA-Gly-GCC and CBX3. Results: tiRNA-Gly-GCC is upregulated in synthetic VSMCs, atherosclerotic arteries, plasma and the balloon injured carotid artery of rats. Functionally, the inhibition of tiRNA-Gly-GCC represses VSMCs proliferation, migration, and reversed dedifferentiation, whereas the overexpression of tiRNA-Gly- GCC have contrary effects. Mechanistically, tiRNA-Gly-GCC performs these functions on VSMCs via downregulating the expression of CBX3. Finally, the inhibition of tiRNA-Gly-GCC could ameliorate neointimal formation after vascular injury in vivo . Conclusions: In conclusion, tiRNA-Gly-GCC is a mediator of VSMCs phenotypic switching by targeting CBX3, inhibition of tiRNA-Gly-GCC suppresses neointimal formation.

Abstract 323: Rspo2 Overexpression Attenuates Hepatic Lipid Accumulation And Atherosclerosis

Aims: We have recently reported elevated RSPO2 levels in human and murine atherosclerotic arteries and discovered its anti-lymphangiogenic potential. However, the precise role of RSPO2 in atherosclerosis is not known. In this study, we investigated the effects of RSPO2 overexpression on hepatosteatosis and atherosclerosis development. Methods and Results: Atheroprone ♂ and ♀ Apoe -/- mice were injected with AAV8- GFP or AAV8- Rspo2 , fed a Western diet for 12 weeks, and analyzed for hepatic lipid accumulation and atherosclerotic lesion formation. Our quantitative RT-PCR data revealed increased Rspo2 mRNA expression in the liver, kidney and spleen of AAV8- Rspo2 -injected mice compared with control mice. Oil Red O (ORO) staining showed reduced hepatic lipid deposition in mice injected with AAV8- Rspo2 compared with AAV8- GFP mice. Additionally, there were reduced levels of hepatic triglyceride, non-esterified fatty acid, and lipid peroxidation in Rspo2 -overexpressing mice. Rspo2 overexpression reduced hepatic fibrosis and macrophage accumulation as indicated by reduced expression of SMA and CD68 in liver tissue. Additionally, decreased mRNA expression of proinflammatory and cholesterol metabolism-related genes was found in liver of AAV8- Rspo2 -injected mice. En face ORO staining of aortae and aortic root sections demonstrated suppressed atherosclerosis in mice with Rspo2 overexpression. Interestingly, AAV8- Rspo2 -injected mice had decreased weight gain over the course of Western diet feeding in comparison to control mice, however, no differences in fasting blood glucose and plasma total cholesterol levels were observed between the two groups. Conclusions: Taken together, these findings suggest that global Rspo2 overexpression in hypercholesterolemic mice suppresses hepatic lipid accumulation and reduces atherosclerosis.

A Case report of Resistant Hypertension due to Renal Artery Stenosis: Long Term Sufferings of a Middle-Aged Gentleman

Atherosclerotic renal artery stenosis is the leading cause of reno-vascular hypertension and is prevalent in elderly patients (over 65 years) and those with resistant hypertension. This article presents a case report of a 60-year-old gentleman who presented with resistant hypertension resulting in heart failure and significant morbidity. The patient's medical history included frequent hospitalizations with uncontrolled hypertension, flash pulmonary edema and heart failure. Despite multiple hospitalizations, the underlying cause of his condition remained unrecognized until further investigation revealed left sided renal artery stenosis as the culprit lesion. Successful renal artery angioplasty resulted in the resolution of the patient's high blood pressure and improvement of general well-being. This case highlights the potential for resistant hypertension due to renal artery stenosis to be overlooked, particularly in patients with multiple comorbidity. It is important to consider the possibility of renal artery stenosis in patients with uncontrolled blood pressure with recurrent pulmonary oedema, not responding to multiple anti-hypertensive drugs in the highest possible dose. Bangladesh J Medicine 2023; 34(2): 163-167

Safety and efficacy of endovascular recanalization for symptomatic non-acute atherosclerotic intracranial large artery occlusion.

The optimal treatment for patients with symptomatic non-acute atherosclerotic intracranial large artery occlusion (ILAO) despite medical treatment is not well established. We aimed to assess the safety, efficacy, and feasibility of angioplasty and stenting for these patients. A total of 251 consecutive patients with symptomatic non-acute atherosclerotic ILAO treated with interventional recanalization were retrospectively collected in our center from March 2015 to August 2021. The rate of successful recanalization, perioperative complications, and follow-up outcomes were evaluated. Successful recanalization was achieved in 88.4% (222/251) of the patients. A total of 24 (24/251, 9.6%) symptomatic complications occurred among 251 procedures. In the 193 patients with clinical follow-up during 19.0 ± 14.7 months, 11 (11/193, 5.7%) patients developed ischemic stroke and four (4/193, 2.1%) patients developed transient ischemic attack (TIA). In the 106 patients with vascular imaging follow-up during 6.8 ± 6.6 months, seven (7/106, 6.6%) patients had restenosis and 10 (10/106, 9.4%) patients had reocclusion. This study suggests that interventional recanalization may be a feasible, basically safe, and an effective alternative in carefully selected patients with symptomatic non-acute atherosclerotic ILAO who have failed medical management.

Restoration of normal blood flow in atherosclerotic arteries promotes plaque stabilization

Blood flow is a key regulator of atherosclerosis. Disturbed blood flow promotes atherosclerotic plaque development, whereas normal blood flow protects against plaque development. We hypothesized that normal blood flow is also therapeutic, if it were able to be restored within atherosclerotic arteries. Apolipoprotein E-deficient (ApoE-/-) mice were initially instrumented with a blood flow-modifying cuff to induce plaque development and then five weeks later the cuff was removed to allow restoration of normal blood flow. Plaques in decuffed mice exhibited compositional changes that indicated increased stability compared to plaques in mice with the cuff maintained. The therapeutic benefit of decuffing was comparable to atorvastatin and the combination had an additive effect. In addition, decuffing allowed restoration of lumen area, blood velocity, and wall shear stress to near baseline values, indicating restoration of normal blood flow. Our findings demonstrate that the mechanical effects of normal blood flow on atherosclerotic plaques promote stabilization.

A vein bypass first versus a best endovascular treatment first revascularisation strategy for patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation procedure to restore limb perfusion (BASIL-2): an open-label, randomised, multicentre, phase 3 trial

Chronic limb-threatening ischaemia is the severest manifestation of peripheral arterial disease and presents with ischaemic pain at rest or tissue loss (ulceration, gangrene, or both), or both. We compared the effectiveness of a vein bypass first with a best endovascular treatment first revascularisation strategy in terms of preventing major amputation and death in patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion. Bypass versus Angioplasty for Severe Ischaemia of the Leg (BASIL)-2 was an open-label, pragmatic, multicentre, phase 3, randomised trial done at 41 vascular surgery units in the UK (n=39), Sweden (n=1), and Denmark (n=1). Eligible patients were those who presented to hospital-based vascular surgery units with chronic limb-threatening ischaemia due to atherosclerotic disease and who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion. Participants were randomly assigned (1:1) to receive either vein bypass (vein bypass group) or best endovascular treatment (best endovascular treatment group) as their first revascularisation procedure through a secure online randomisation system. Participants were excluded if they had ischaemic pain or tissue loss considered not to be primarily due to atherosclerotic peripheral artery disease. Most vein bypasses used the great saphenous vein and originated from the common or superficial femoral arteries. Most endovascular interventions comprised plain balloon angioplasty with selective use of plain or drug eluting stents. Participants were followed up for a minimum of 2 years. Data were collected locally at participating centres. In England, Wales, and Sweden, centralised databases were used to collect information on amputations and deaths. Data were analysed centrally at the Birmingham Clinical Trials Unit. The primary outcome was amputation-free survival defined as time to first major (above the ankle) amputation or death from any cause measured in the intention-to-treat population. Safety was assessed by monitoring serious adverse events up to 30-days after first revascularisation. The trial is registered with the ISRCTN registry, ISRCTN27728689. Between July 22, 2014, and Nov 30, 2020, 345 participants (65 [19%] women and 280 [81%] men; median age 72·5 years [62·7-79·3]) with chronic limb-threatening ischaemia were enrolled in the trial and randomly assigned: 172 (50%) to the vein bypass group and 173 (50%) to the best endovascular treatment group. Major amputation or death occurred in 108 (63%) of 172 patients in the vein bypass group and 92 (53%) of 173 patients in the best endovascular treatment group (adjusted hazard ratio [HR] 1·35 [95% CI 1·02-1·80]; p=0·037). 91 (53%) of 172 patients in the vein bypass group and 77 (45%) of 173 patients in the best endovascular treatment group died (adjusted HR 1·37 [95% CI 1·00-1·87]). In both groups the most common causes of morbidity and death, including that occurring within 30 days of their first revascularisation, were cardiovascular (61 deaths in the vein bypass group and 49 in the best endovascular treatment group) and respiratory events (25 deaths in the vein bypass group and 23 in the best endovascular treatment group; number of cardiovascular and respiratory deaths were not mutually exclusive). In the BASIL-2 trial, a best endovascular treatment first revascularisation strategy was associated with a better amputation-free survival, which was largely driven by fewer deaths in the best endovascular treatment group. These data suggest that more patients with chronic limb-threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion should be considered for a best endovascular treatment first revascularisation strategy. UK National Institute of Health Research Health Technology Programme.

Renovascular Hypertension with Progressive Atherosclerotic Renal Artery Stenosis in an Elderly Patient with Known Fibromuscular Dysplasia: A Case Report.

BACKGROUND Atherosclerotic renal artery stenosis (ARAS) and renovascular fibromuscular dysplasia (FMD) are 2 of the most common etiologies of renovascular hypertension. They have different pathophysiologies, risk factors, presentations, and treatment options. However, as our population ages, it can become increasingly common to see patients who previously had FMD who develop ARAS at an advanced age, indicated by recurrent renovascular hypertension. CASE REPORT We present a case of a 66-year-old female patient who, in 2007, had presented with uncontrolled hypertension. She underwent magnetic resonance angiography and was found to have bilateral FMD, for which she received balloon angioplasty to a severe lesion on the mid-right renal artery and subsequently had normalization of blood pressures and resolution of symptoms. In 2021 she returned with uncontrolled hypertension while being treated with 3 antihypertensives. Bilateral renal arteriography revealed new severe ostial stenosis of the left renal artery and a patent right renal artery in which balloon angioplasty was performed 14 years ago. Based on the angiographic pattern of this new left RAS, we concluded this lesion was caused by atherosclerosis. The left ostial lesion was treated with a bare-metal stent and the patient was continued on antihypertensive medication and statin; at follow-up 4 months later, her blood pressures had normalized. CONCLUSIONS This case features a patient who developed severe ARAS with underlying history of bilateral renal artery FMD. Clinicians need to be aware that in patients with FMD, worsening renovascular hypertension at an advanced age could indicate the development of new hemodynamically significant ARAS. These patients need repeat diagnostic testing and treatment with medial optimization with or without endovascular revascularization in the appropriate clinical setting.

Stent Implantation and Thromboendarterectomy for the Common Femoral Artery in Real-World Practice.

To compare the outcomes of thromboendarterectomy (TEA) and endovascular therapy (EVT) with stenting for patients with atherosclerotic common femoral artery (CFA) occlusive disease. From a retrospective registry of 1193 consecutive patients with CFA treatment performed between 2018 and 2020 at 66 institutions in Japan, we identified patients who underwent TEA (n=432) or stent implantation (n=157). The primary outcome measures were the 1-year primary patency of TEA versus stenting with propensity score matching. The secondary outcome measures were perioperative complications, length of hospital stay, any reintervention, limb salvage, and overall survival. Interaction analysis for primary patency was performed with propensity score stratification to determine the appropriate target population for CFA stenting. Propensity score matching extracted 101 pairs (101 patients in the EVT group and 253 patients in the TEA group). The 1-year primary patency rate was significantly higher in the TEA cohort (92.8% vs 84.6%, p=0.006). The freedom from reintervention rate was also significantly higher in the TEA cohort (94.0% vs 89.9%, p=0.030). However, the 1-year limb salvage (98.7% vs 100.0%, p=0.32), 1-year overall survival (90.8% vs 85.0%, p=0.14), and frequency of perioperative complications were not significantly different between the cohorts (6.9% vs 14.2%, p=0.10). Based on interaction analysis, the superiority of TEA over EVT in terms of patency was less apparent in patients with advanced age and chronic heart failure. Thromboendarterectomy was superior to stenting in terms of primary patency and freedom from revascularization at 1 year. There was no significant difference in the incidence of perioperative complications between both groups. Thromboendarterectomy may be recommended as the standard treatment strategy for patients with atherosclerotic CFA disease, whereas stenting may be considered for patients with advanced age and chronic heart failure. Thromboendarterectomy compared to stenting was the preferred revascularization strategy for patients with CFA disease in terms of primary patency and freedom from target lesion revascularization during the 1st year. The difference was attenuated in subgroups with advanced age (85 years or older) or chronic heart failure, thus stenting may be considered in patients with these backgrounds.

Periprocedural Outcomes of Rotational Atherectomy-Assisted Balloon Angioplasty in Isolated Atherosclerotic Popliteal Artery Lesions: The ISO-POP Trial.

Treatment of calcified popliteal artery lesions represents an ongoing challenge for vascular specialists. Biomechanical forces of external compression, torsion and elongation that occur with locomotion in the popliteal segment can lead to stent fractures and occlusions. The aim of our study was to assess the procedural success rate of atherectomy in combination with balloon angioplasty for isolated calcified popliteal artery lesions. Between January 2020 and December 2022, 62 patients with isolated atherosclerotic lesions of the popliteal artery underwent endovascular treatment by use of rotational atherectomy (Phoenix, Philips USA, (subgroup A) or Jetstream, Boston USA, (subgroup B), atherectomy systems) and additional balloon angioplasty in two vascular centers. The primary outcome measures were: 1. periprocedural clinical and technical success (<30% residual stenosis and no need for bailout stenting due to flow-limiting dissection) and 2. postprocedural increase in the ankle brachial index of more than 0.1. The overall rate of bailout stenting was 4.8%, whereas the procedural success rate was 98.4%. The rate of procedural complications included 3.7% and 5.7% peripheral embolizations in the subgroups A and B, respectively, and no vessel perforations were noted. All embolizations were successfully treated by catheter aspiration or capture in the pre-treatment placed filter system. In addition, 1 (3.7%) pseudoaneurysm in the groin was reported in subgroup A and treated by surgical means. Median ABI of the affected limbs improved from 0.55 (0.2) to 0.70 (0.2) in subgroup A and from 0.50 (0.2) to 0.95 (0.1) in subgroup B (DABI of 0.15 versus 0.45, p < 0.001). The combination of rotational atherectomy and balloon angioplasty in the popliteal artery showed reproducible outcomes in 2 centers, with low incidence of complications and low rates of bail-out stenting. These findings may contribute to more liberal use of such devices especially in segments with high risk for stent factures and occlusions.

Surgical, Endovascular, and Multimodal Approaches to the Management of Atherosclerotic Common Femoral Artery Disease.

Common femoral artery disease is at the heart of nearly all treatment algorithms and decisions for patients with symptomatic peripheral arterial disease. Surgical endarterectomy has been the mainstay of common femoral treatment with a wealth of data supporting its safety, efficacy, and durability. Advances in endovascular technology and techniques for the management of iliac and superficial femoral artery disease has resulted in a paradigm shift in management. The common femoral artery has been aptly named a "no stent zone" due to anatomic and disease-specific challenges that have limited the role for endovascular techniques. New technology and techniques in the endovascular management of common femoral disease seek to change our treatment strategies. A multimodal approach utilizing a combination of angioplasty, atherectomy, and stenting has been shown most beneficial, although limited long-term data leave durability an unanswered question. While surgical treatment remains the gold standard, advances in the endovascular approach will certainly continue to improve outcomes. As truly isolated common femoral disease is a rarity, a collaborative approach combining all benefits of open and endovascular techniques in the treatment of peripheral arterial disease is essential.

Integrated single-cell RNA-seq analysis reveals the vital cell types and dynamic development signature of atherosclerosis.

Introduction: In the development of atherosclerosis, the remodeling of blood vessels is a key process involving plaque formation and rupture. So far, most reports mainly believe that macrophages, smooth muscle cells, and endothelial cells located at the intima and media of artery play the key role in this process. Few studies had focused on whether fibroblasts located at adventitia are involved in regulating disease process. Methods and results: In this study, we conducted in-depth analysis of single-cell RNA-seq data of the total of 18 samples from healthy and atherosclerotic arteries. This study combines several analysis methods including transcription regulator network, cell-cell communication network, pseudotime trajectory, gene set enrichment analysis, and differential expression analysis. We found that SERPINF1 is highly expressed in fibroblasts and is involved in the regulation of various signaling pathways. Conclusion: Our research reveals a potential mechanism of atherosclerosis, SERPINF1 regulates the formation and rupture of plaques through the Jak-STAT signaling pathway, which may provide new insights into the pathological study of disease. Moreover, we suggest that SRGN and IGKC as potential biomarkers for unstable arterial plaques.

The translational landscape of human vascular smooth muscle cells identifies novel short open reading frame-encoded peptide regulators for phenotype alteration.

The plasticity of vascular smooth muscle cells (VSMCs) enables them to alter phenotypes under various physiological and pathological stimuli. The alteration of VSMC phenotype is a key step in vascular diseases, including atherosclerosis. Although the transcriptome shift during VSMC phenotype alteration has been intensively investigated, uncovering multiple key regulatory signalling pathways, the translatome dynamics in this cellular process, remain largely unknown. Here, we explored the genome-wide regulation at the translational level of human VSMCs during phenotype alteration. We generated nucleotide-resolution translatome and transcriptome data from human VSMCs undergoing phenotype alteration. Deep sequencing of ribosome-protected fragments (Ribo-seq) revealed alterations in protein synthesis independent of changes in messenger ribonucleicacid levels. Increased translational efficiency of many translational machinery components, including ribosomal proteins, eukaryotic translation elongation factors and initiation factors were observed during the phenotype alteration of VSMCs. In addition, hundreds of candidates for short open reading frame-encoded polypeptides (SEPs), a class of peptides containing 200 amino acids or less, were identified in a combined analysis of translatome and transcriptome data with a high positive rate in validating their coding capability. Three evolutionarily conserved SEPs were further detected endogenously by customized antibodies and suggested to participate in the pathogenesis of atherosclerosis by analysing the transcriptome and single cell RNA-seq data from patient atherosclerotic artery samples. Gain- and loss-of-function studies in human VSMCs and genetically engineered mice showed that these SEPs modulate the alteration of VSMC phenotype through different signalling pathways, including the mitogen-activated protein kinase pathway and p53 pathway. Our study indicates that an increase in the capacity of translation, which is attributable to an increased quantity of translational machinery components, mainly controls alterations of VSMC phenotype at the level of translational regulation. In addition, SEPs could function as important regulators in the phenotype alteration of human VSMCs.

Spinal artery infarction.

Spinal cord infarctions are rare, and the symptoms vary depending on location and size. One patient presented with severe neck pain and paresis of the left arm. Compression of a cervical nerve root was initially suspected, but the progression of symptoms and MRI findings gradually suggested a different aetiology.

Staged endovascular recanalization for symptomatic atherosclerotic non-acutely occluded internal carotid artery

Symptomatic "non-acutely" occluded internal carotid artery (NAOICA) results in stroke, cognitive impairment, and hemicerebral atrophy through cerebral hypoperfusion and artery-to-artery embolism. Atherosclerosis is the main cause of NAOICA. Conventional one-stage endovascular recanalization showed effectiveness but was plagued by many challenges. This retrospective analysis reports the technical feasibility and outcomes of the staged endovascular recanalization in patients with NAOICA. Eight consecutive patients with atherosclerotic NAOICA and ipsilateral ischemic stroke within 3 months between January 2019 and March 2022 were retrospectively reviewed. The patients (all males, with a mean age of 64.6 years) underwent staged endovascular recanalization 13 to 56 days after documented occlusion by imaging techniques (mean 28.8 days); the mean follow-up period was 20 months (range: 6-28). The approach of the staged intervention was as follows. In the first stage, the occluded ICA was successfully recanalized using the simple small balloon dilation technique. In the second stage, angioplasty with a stent implant was performed with >50% residual stenosis in the initial segment or ≥70% residual stenosis in the C2-C5 segment. The technical success rate, the incidence of clinical adverse events (any stroke, death, cerebral hyperperfusion), and long-term in-stent stenosis (ISR) and reocclusion rates were evaluated. Technical success was achieved in seven patients, with early reocclusion occurring in one patient after the first-stage intervention. There were no adverse events observed within 30 days (0%), and long-term reocclusion and long-term ISR rates were both 14% (1/7). However, all patients developed iatrogenic arterial dissections during the first stage, indicating the challenge of reaching the true lumen through the occlusion site without damaging the intima. Based on the National Heart, Lung and Blood Institute (NHLBI) classification, there were two type A, four type B, three type C, and two type D dissections. The mean time interval between the two stages was 46.1 days (21-152 days). All type A and B dissections resolved spontaneously after ≥3 weeks of dual antiplatelet therapy, whereas most type C and all type D dissections did not heal spontaneously before the second stage. Also, one type C dissection led to reocclusion. This observation suggested that occlusions without flow limit and persistent vessel staining or extravasation could be clinically observed, while severe dissections (characterized as type C or greater) required prompt stenting rather than conservative treatment. Performing high-resolution MRI preoperatively to exclude fresh thrombus in the occluded vessel segment is indispensable in selecting appropriate candidates for endovascular recanalization. This could avoid downstream embolism during the interventional procedure. This retrospective study found that staged endovascular recanalization for symptomatic atherosclerotic NAOICA may be feasible with an acceptable technical success rate and a low complication rate in the selected candidates.

BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility.

The transcription factor BTB and CNC homology 1(BACH1) has been linked to coronary artery disease risk by human genome-wide association studies, but little is known about the role of BACH1 in vascular smooth muscle cell (VSMC) phenotype switching and neointima formation following vascular injury. Therefore, this study aims to explore the role of BACH1 in vascular remodeling and its underlying mechanisms. BACH1 was highly expressed in human atherosclerotic plaques and has high transcriptional factor activity in VSMCs of human atherosclerotic arteries. VSMC-specific loss of Bach1 in mice inhibited the transformation of VSMC from contractile to synthetic phenotype and VSMC proliferation and attenuated the neointimal hyperplasia induced by wire injury. Mechanistically, BACH1 suppressed chromatin accessibility at the promoters of VSMC marker genes via recruiting histone methyltransferase G9a and cofactor YAP and maintaining the H3K9me2 state, thereby repressing VSMC marker genes expression in human aortic smooth muscle cells (HASMCs). BACH1-induced repression of VSMC marker genes was abolished by the silencing of G9a or YAP. Thus, these findings demonstrate a crucial regulatory role of BACH1 in VSMC phenotypic transition and vascular homeostasis and shed light on potential future protective vascular disease intervention via manipulation of BACH1.

Endovascular interventions in symptomatic atherosclerotic renal artery disease

Endovascular interventions in symptomatic atherosclerotic renal artery disease

Abstract Number ‐ 216: Limb‐Shaking Transient Ischemic Attack in the Setting of Moyamoya Disease

Introduction Moyamoya disease (MMD) is a cerebrovascular disorder characterized by progressive narrowing of the large intracranial arteries, primarily the internal carotid artery (ICA) and its branches, with secondary development of prominent small‐vessel collaterals. Limb shaking is a rare manifestation of transient ischemic attack (TIA) that is characterized by brief, irregular, involuntary jerking of the arms or legs and momentary disorientation without complete loss of consciousness. It is mainly associated with high grade carotid stenosis. In rare cases, limb‐shaking TIA can occur in the setting of MMD. Methods The patient was identified in routine clinical practice. Results A woman in her 50s presented with a six‐year history of progressive weakness below the neck when standing and initiating movement. These episodes were followed by violent shaking of her arms and legs that lasted several seconds to minutes. She reported transient confusion after the events, but no seizure activity was seen on multiple EEGs, and anti‐epileptic drugs (AEDs) failed to alleviate her symptoms. Further neurological workup included a MR angiogram of the brain that was suggestive of MMD. Catheter angiography confirmed bilateral occlusion of the M1 segments of the middle cerebral arteries (MCAs) and the A1 segment of the left anterior cerebral artery (ACA). There was neovascularization in the same territories with significant collateral flow from the posterior circulation. She was diagnosed with bilateral limb‐shaking TIA in the setting of MMD. She recently underwent two revascularization procedures, a left superficial temporal artery (STA) to middle cerebral artery (MCA) bypass and a right sided encephaloduroarteriosynangiosis (EDAS). Conclusions Limb‐shaking TIA is predominantly associated with severe atherosclerotic extracranial carotid artery stenosis. In rare cases, the limb‐shaking episodes are caused by cerebral hypoperfusion secondary to severe stenosis of the ICAs, and their branches, in the setting of moyamoya disease. Treatment of limb‐shaking TIA to prevent further brain ischemia includes adjustment of fluid intake, careful blood pressure management to avoid episodes of relative brain hypoperfusion, and revascularization procedures. Revascularization is also the most effective method of treating MMD and patients will often experience improvement of their symptoms within one year. Early recognition of limb‐shaking TIA in MMD is critical to avoid unnecessary and potentially harmful treatments (e.g. AEDs), provide patients with accurate explanations of their symptoms, and ensure timely administration of the appropriate treatments.