Use of resuscitative endovascular balloon occlusion of the aorta (REBOA) for trauma and its performance in Japan over the past 18 years: a nationwide descriptive study.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been used to control massive hemorrhages. Although there is no consensus on the efficacy of REBOA, it remains an option as a bridging therapy in non-trauma centers where trauma surgeons are not available. To better understand the current landscape of REBOA application, we examined changes in its usage, target population, and treatment outcomes in Japan, where immediate hemostasis procedures sometimes cannot be performed. METHODS: This retrospective observational study used the Japan Trauma Data Bank data. All cases in which REBOA was performed between January 2004 and December 2021 were included. The primary outcome was the in-hospital mortality rate. We analyzed mortality trends over time according to the number of cases, number of centers, severity of injury, and overall and subgroup mortality associated with REBOA usage. We performed a logistic analysis of mortality trends over time, adjusting for probability of survival based on the trauma and injury severity score. RESULTS: Overall, 2557 patients were treated with REBOA and were deemed eligible for inclusion. The median age of the participants was 55 years, and male patients constituted 65.3% of the study population. Blunt trauma accounted for approximately 93.0% of the cases. The number of cases and facilities that used REBOA increased until 2019. While the injury severity score and revised trauma score did not change throughout the observation period, the hospital mortality rate decreased from 91.3 to 50.9%. The REBOA group without severe head or spine injuries showed greater improvement in mortality than the all-patient group using REBOA and all-trauma patient group. The greatest improvement in mortality was observed in patients with systolic blood pressure ≥ 80 mmHg. The adjusted odds ratios for hospital mortality steadily declined, even after adjusting for the probability of survival. CONCLUSIONS: While there was no significant change in patient severity, mortality of patients treated with REBOA decreased over time. Further research is required to determine the reasons for these improvements in trauma care.

Fluoride impairs vascular smooth muscle A7R5 cell lines via disrupting amino acids metabolism.

Given the insidious and high-fatality nature of cardiovascular diseases (CVDs), the emergence of fluoride as a newly identified risk factor demands serious consideration alongside traditional risk factors. While vascular smooth muscle cells (VSMCs) play a pivotal role in the progression of CVDs, the toxicological impact of fluoride on VSMCs remains largely uncharted. In this study, we constructed fluorosis model in SD rats and A7R5 aortic smooth muscle cell lines to confirm fluoride impaired VSMCs. Fluoride aggravated the pathological damage of rat aorta in vivo. Then A7R5 were exposed to fluoride with concentration ranging from 0 to 1200 µmol/L over a 24-h period, revealing a dose-dependent inhibition of cell proliferation and migration. The further metabolomic analysis showed alterations in metabolite profiles induced by fluoride exposure, notably decreasing organic acids and lipid molecules level. Additionally, gene network analysis underscored the frequency of fluoride's interference with amino acids metabolism, potentially impacting the tricarboxylic acid (TCA) cycle. Our results also highlighted the ATP-binding cassette (ABC) transporters pathway as a central element in VSMC impairment. Moreover, we observed a dose-dependent increase in osteopontin (OPN) and α-smooth muscle actin (α-SMA) mRNA level and a dose-dependent decrease in ABC subfamily C member 1 (ABCC1) and bestrophin 1 (BEST1) mRNA level. These findings advance our understanding of fluoride as a CVD risk factor and its influence on VSMCs and metabolic pathways, warranting further investigation into this emerging risk factor.

Removal of endothelial surface-associated von villebrand factor suppresses accelerate datherosclerosis after myocardial infarction.

BACKGROUND: Thromboinflammation involving platelet adhesion to endothelial surface-associated von Willebrand factor (VWF) has been implicated in the accelerated progression of non-culprit plaques after MI. The aim of this study was to use arterial endothelial molecular imaging to mechanistically evaluate endothelial-associated VWF as a therapeutic target for reducing remote plaque activation after myocardial infarction (MI). METHODS: Hyperlipidemic mice deficient for the low-density lipoprotein receptor and Apobec-1 underwent closed-chest MI and were treated chronically with either: (i) recombinant ADAMTS13 which is responsible for proteolytic removal of VWF from the endothelial surface, (ii) N-acetylcysteine (NAC) which removes VWF by disulfide bond reduction, (iii) function-blocking anti-factor XI (FXI) antibody, or (iv) no therapy. Non-ischemic controls were also studied. At day 3 and 21, ultrasound molecular imaging was performed with probes targeted to endothelial-associated VWF A1-domain, platelet GPIbα, P-selectin and vascular cell adhesion molecule-1 (VCAM-1) at lesion-prone sites of the aorta. Histology was performed at day 21. RESULTS: Aortic signal for P-selectin, VCAM-1, VWF, and platelet-GPIbα were all increased several-fold (p < 0.01) in post-MI mice versus sham-treated animals at day 3 and 21. Treatment with NAC and ADAMTS13 significantly attenuated the post-MI increase for all four molecular targets by > 50% (p < 0.05 vs. non-treated at day 3 and 21). On aortic root histology, mice undergoing MI versus controls had 2-4 fold greater plaque size and macrophage content (p < 0.05), approximately 20-fold greater platelet adhesion (p < 0.05), and increased staining for markers of platelet transforming growth factor-ß1 signaling. Accelerated plaque growth and inflammatory activation was almost entirely prevented by ADAMTS13 and NAC. Inhibition of FXI had no significant effect on molecular imaging signal or plaque morphology. CONCLUSIONS: Plaque inflammatory activation in remote arteries after MI is strongly influenced by VWF-mediated platelet adhesion to the endothelium. These findings support investigation into new secondary preventive therapies for reducing non-culprit artery events after MI.

Angulation and curvature of aortic landing zone affect implantation depth in transcatheter aortic valve implantation.

In transcatheter aortic valve implantation (TAVI), final device position may be affected by device interaction with the whole aortic landing zone (LZ) extending to ascending aorta. We investigated the impact of aortic LZ curvature and angulation on TAVI implantation depth, comparing short-frame balloon-expanding (BE) and long-frame self-expanding (SE) devices. Patients (n = 202) treated with BE or SE devices were matched based on one-to-one propensity score. Primary endpoint was the mismatch between the intended (HPre) and the final (HPost) implantation depth. LZ curvature and angulation were calculated based on the aortic centerline trajectory available from pre-TAVI computed tomography. Total LZ curvature ( k L Z , t o t ) and LZ angulation distal to aortic annulus ( α L Z , D i s t a l ) were greater in the SE compared to the BE group (P < 0.001 for both). In the BE group, HPost was significantly higher than HPre at both cusps (P < 0.001). In the SE group, HPost was significantly deeper than HPre only at the left coronary cusp (P = 0.013). At multivariate analysis, α L Z , D i s t a l was the only independent predictor (OR = 1.11, P = 0.002) of deeper final implantation depth with a cut-off value of 17.8°. Aortic LZ curvature and angulation significantly affected final TAVI implantation depth, especially in high stent-frame SE devices reporting, upon complete release, deeper implantation depth with respect to the intended one.

Assessment of aortic dilatation in Chinese children and adolescents with Turner syndrome: a single center experience.

BACKGROUND: Patients with Turner syndrome (TS) face an increased risk of developing aortic dilatation (AD), but diagnosing AD in children presents greater complexity compared to adults. This study aimed to investigate the application of various assessment indicators of AD in Chinese children and adolescents with TS. METHODS: This study included TS patients admitted to Shenzhen Children's Hospital from 2017 to 2022. Cardiovascular lesions were diagnosed by experienced radiologists. Patients without structural heart disease were divided into different body surface area groups, then the Chinese TS population Z-score (CHTSZ-score) of the ascending aorta was calculated and compared with other indicators such as aortic size index (ASI), ratio of the ascending to descending aortic diameter (A/D ratio), and TSZ-score (Quezada's method). RESULTS: A total of 115 TS patients were included, with an average age of 10.0 ± 3.7 years. The incidences of the three most serious cardiovascular complications were 9.6% (AD), 10.4% (coarctation of the aorta, CoA), and 7.0% (bicuspid aortic valve, BAV), respectively. The proportion of developing AD in TS patients aged ≥ 10 years was higher than that in those < 10 years old (16.6% vs. 1.8%, P = 0.009), and the proportion of patients with CoA or BAV who additionally exhibited AD was higher than those without these conditions (31.6% vs. 5.2%, P < 0.001). The ASI, A/D ratio, TSZ-score, and CHTSZ-score of the 11 patients with AD were 2.27 ± 0.40 cm/m2, 1.90 ± 0.37, 1.28 ± 1.08, and 3.07 ± 2.20, respectively. Among the AD patients, only 3 cases had a TSZ-score ≥ 2, and 2 cases had a TSZ-score ≥ 1. However, based on the assessment using the CHTSZ-score, 6 patients scored ≥ 2, and 5 patients scored ≥ 1. In contrast, the TSZ-score generally underestimated the aortic Z-scores in Chinese children with TS compared to the CHTSZ-score. CONCLUSIONS: The applicability of ASI and A/D ratio to children with TS is questionable, and racial differences can affect the assessment of TSZ-score in the Chinese population. Therefore, establishing the CHTSZ-score specifically tailored for Chinese children and adolescents is of paramount importance.

Aortic pulse wave analysis and functional capacity of heart transplantation candidates: a pilot study.

We compared cardiovascular parameters obtained with the Mobil-O-Graph and functional capacity assessed by the Duke Activity Status Index (DASI) before and after Heart Transplantation (HT) and also compared the cardiovascular parameters and the functional capacity of candidates for HT with a control group. Peripheral and central vascular pressures increased after surgery. Similar results were observed in cardiac output and pulse wave velocity. The significant increase in left ventricular ejection fraction (LVEF) postoperatively was not followed by an increase in the functional capacity. 24 candidates for HT and 24 controls were also compared. Functional capacity was significantly lower in the HT candidates compared to controls. Stroke volume, systolic, diastolic, and pulse pressure measured peripherally and centrally were lower in the HT candidates when compared to controls. Despite the significant increase in peripheral and central blood pressures after surgery, the patients were normotensive. The 143.85% increase in LVEF in the postoperative period was not able to positively affect functional capacity. Furthermore, the lower values of LVEF, systolic volume, central and peripheral arterial pressures in the candidates for HT are consistent with the characteristics signs of advanced heart failure, negatively impacting functional capacity, as observed by the lower DASI score.

Updated 2022 ACC/AHA Guideline Improves Concordance Between TTE and CT in Monitoring Marfan Snydrome and Related Disorders, but Relevant Measurement Differences Remain Frequent.

Background: Patients diagnosed with Marfan syndrome or a related syndrome require frequent aorta monitoring using imaging techniques like transthoracic echocardiography (TTE) and computed tomography (CT). Accurate aortic measurement is crucial, as even slight enlargement (>2 mm) often necessitates surgical intervention. The 2022 ACC/AHA guideline for Aortic Disease Diagnosis and Management includes updated imaging recommendations. We aimed to compare these with the 2010 guideline. Methods: This retrospective study involved 137 patients with Marfan syndrome or a related disorder, undergoing TTE and ECG-triggered CT. Aortic diameter measurements were taken based on the old 2010 guideline (TTE: inner edge to inner edge, CT: external diameter) and the new 2022 guideline (TTE: leading edge to leading edge, CT: internal diameter). Bland-Altman plots compared measurement differences. Results: Using the 2022 guideline significantly reduced differences outside the clinical agreement limit from 49% to 26% for the aortic sinus and from 41% to 29% for the ascending aorta. Mean differences were -0.30 mm for the aortic sinus and +1.12 mm for the ascending aorta using the 2022 guideline, compared to -2.66 mm and +1.21 mm using the 2010 guideline. Conclusion: This study demonstrates for the first time that the 2022 ACC/AHA guideline improves concordance between ECG-triggered CT and TTE measurements in Marfan syndrome patients, crucial for preventing life-threatening aortic complications. However, the frequency of differences >2 mm remains high. Clinical Relevance/Application: Accurate aortic diameter measurement is vital for patients at risk of fatal aortic complications. While the 2022 guideline enhances concordance between imaging modalities, frequent differences >2 mm persist, potentially impacting decisions on aortic repair. The risk of repeat radiation exposure from ECG-triggered CT, considered the 'gold standard', continues to be justified.

Effects of Chronic Inflammatory Activation of Murine and Human Arterial Endothelial Cells at Normal Lipoprotein and Cholesterol Levels In Vivo and In Vitro.

The activation of endothelial cells is crucial for immune defense mechanisms but also plays a role in the development of atherosclerosis. We have previously shown that inflammatory stimulation of endothelial cells on top of elevated lipoprotein/cholesterol levels accelerates atherogenesis. The aim of the current study was to investigate how chronic endothelial inflammation changes the aortic transcriptome of mice at normal lipoprotein levels and to compare this to the inflammatory response of isolated endothelial cells in vitro. We applied a mouse model expressing constitutive active IκB kinase 2 (caIKK2)-the key activator of the inflammatory NF-κB pathway-specifically in arterial endothelial cells and analyzed transcriptomic changes in whole aortas, followed by pathway and network analyses. We found an upregulation of cell death and mitochondrial beta-oxidation pathways with a predicted increase in endothelial apoptosis and necrosis and a simultaneous reduction in protein synthesis genes. The highest upregulated gene was ACE2, the SARS-CoV-2 receptor, which is also an important regulator of blood pressure. Analysis of isolated human arterial and venous endothelial cells supported these findings and also revealed a reduction in DNA replication, as well as repair mechanisms, in line with the notion that chronic inflammation contributes to endothelial dysfunction.

Overexpression of miR-204-5p Alleviates Osteogenic Differentiation and Calcification of Human Aortic Vascular Smooth Muscle Cells by Targeting Calcium/Calmodulin-dependent Protein Kinase 1.

ABSTRACT: Vascular calcification (VC), a major complication in chronic kidney disease (CKD), is predominantly driven by osteoblastic differentiation. Recent studies have highlighted the crucial role of microRNAs in CKD's pathogenesis. Here, our research focused on the effects of miR-204-5p and its molecular mechanisms within VC. We initially found a notable decrease in miR-204-5p levels in human aortic vascular smooth muscle cells stimulated with inorganic phosphate, using this as a VC model in vitro. Following the overexpression of miR-204-5p, a decrease in VC was observed, as indicated by alizarin red S staining and measurements of calcium content. This decrease was accompanied by lower levels of the osteogenic marker, runt-related transcription factor 2, and higher levels of α-smooth muscle actin, a marker of contractility. Further investigation showed that calcium/calmodulin-dependent protein kinase 1 (CAMK1), which is a predicted target of miR-204-5p, promotes VC. Conversely, overexpressing miR-204-5p reduced VC by suppressing CAMK1 activity. Overexpressing miR-204-5p also effectively mitigated aortic calcification in an in vivo rat model. In summary, our research indicated that targeting the miR-204-5p/CAMK1 pathway could be a viable strategy for mitigating VC in CKD patients.

Circumferent dissection of the ascending aorta resulting in the occlusion of supra-aortic vessels repaired using the frozen elephant trunk technique - a case report.

BACKGROUND: Our patient presented with acute back pain and dyspnea, without neurological symptoms. The computed tomography (CT) scan showed a circumferent rupture of the ascending aortic intima which was invaginated in the arch and descending aorta. CASE PRESENTATION: A 54-year-old male patient was diagnosed with a Type A aortic dissection. He was immediately transferred to our operation room (OR) from the emergency department of a peripheral hospital. He presented with a circumferential dissection of the ascending aorta originating just distal to the coronary ostia, with the invaginated intimal mass extending through the arch down the descending aorta. In mild hypothermia, the intimal mass was safely extracted and a frozen elephant trunk (FET) procedure was performed. CONCLUSIONS: Despite the extensive dissection affecting the ascending aorta and aortic arch, resulting in partially occluded supra-aortic vessels by an intimal mass, the patient remained without neurological symptoms in the pre- and post-operative period and remains well one year post surgery.

In situ ascending aortic thrombus in a patient with metastatic lung adenocarcinoma and no aortic atherosclerosis or cisplatin exposure: a case report.

BACKGROUND: An ascending aortic thrombus is exceedingly rare. Two instances have been reported in the setting of lung cancer, but only after cisplatin use, which is associated with hypercoagulability. We present the first case of a patient with lung cancer who developed an ascending aortic thrombus without structural risk factors or chemotherapy use. CASE: A 60-year-old white female with significant smoking history presented with several weeks of malaise. A chest computed tomography scan revealed a 2.2-cm right upper lobe mass. As an outpatient, right hilar lymph node immunohistochemistry (IHC) samples via endobronchial ultrasound confirmed thyroid transcription factor-1 adenocarcinoma. After the procedure, the patient endorsed dyspnea and was advised to go to the emergency department. A chest computed tomography angiography identified a new 2.4 × 1.1 × 1.1 cm thrombus within the proximal aortic arch. No pulmonary emboli or intrapulmonary shunts were identified. A hypercoagulable workup was negative. Transthoracic echocardiogram was without left ventricular thrombus, akinesis or hypokinesis, left atrial dilation, or intracardiac shunts. A lower extremity ultrasound was negative for deep vein thrombosis. Given the procedural risk, thrombectomy was deferred. The patient was transitioned to enoxaparin, and a repeat computed tomography for resolution is in process. CONCLUSION: To our knowledge, this is the only case detailing an in situ ascending aortic thrombus in the setting of lung cancer, without structural risk factors, chemotherapy use, or other hypercoagulable comorbidities. Optimal management for an aortic thrombus and malignant disease is less clear. Clinicians should be vigilant for unusual arterial thromboses in patients with high metastatic burden.

Numerical study of hemodynamic flow in the aortic vessel of Williams syndrome patient with congenital heart disease.

Congenital arterial stenosis such as supravalvar aortic stenosis (SVAS) are highly prevalent in Williams syndrome (WS) and other arteriopathies pose a substantial health risk. Conventional tools for severity assessment, including clinical findings and pressure gradient estimations, often fall short due to their susceptibility to transient physiological changes and disease stage influences. Moreover, in the pediatric population, the severity of these and other congenital heart defects (CHDs) often restricts the applicability of invasive techniques for obtaining crucial physiological data. Conversely, evaluating CHDs and their progression requires a comprehensive understanding of intracardiac blood flow. Current imaging modalities, such as blood speckle imaging (BSI) and four-dimensional magnetic resonance imaging (4D MRI) face limitations in resolving flow data, especially in cases of elevated flow velocities. To address these challenges, we devised a computational framework employing zero-dimensional (0D) lumped parameter models coupled with patient-specific reconstructed geometries pre- and post-surgical intervention to execute computational fluid dynamic (CFD) simulations. This framework facilitates the analysis and visualization of intricate blood flow patterns, offering insights into geometry and flow dynamics alterations impacting cardiac function. In this study, we aim to assess the efficacy of surgical intervention in correcting an extreme aortic defect in a patient with WS, leading to reductions in wall shear stress (WSS), maximum velocity magnitude, pressure drop, and ultimately a decrease in cardiac workload.

Multiscale computational model of aortic remodeling following postnatal disruption of TGFß signaling.

The healthy adult aorta is a remarkably resilient structure, able to resist relentless cardiac-induced and hemodynamic loads under normal conditions. Fundamental to such mechanical homeostasis is the mechano-sensitive cell signaling that controls gene products and thus the structural integrity of the wall. Mouse models have shown that smooth muscle cell-specific disruption of transforming growth factor-beta (TGFß) signaling during postnatal development compromises this resiliency, rendering the aortic wall susceptible to aneurysm and dissection under normal mechanical loading. By contrast, disruption of such signaling in the adult aorta appears to introduce a vulnerability that remains hidden under normal loading, but manifests under increased loading as experienced during hypertension. We present a multiscale (transcript to tissue) computational model to examine possible reasons for compromised mechanical homeostasis in the adult aorta following reduced TGFß signaling in smooth muscle cells.

Cardiovascular pathology in vasculitis.

Vasculitides are diseases that can affect any vessel. When cardiac or aortic involvement is present, the prognosis can worsen significantly. Pathological assessment often plays a key role in reaching a definite diagnosis of cardiac or aortic vasculitis, particularly when the clinical evidence of a systemic inflammatory disease is missing. The following review will focus on the main histopathological findings of cardiac and aortic vasculitides.

Ginsenoside Rk1 improves endothelial function in diabetes through activating peroxisome proliferator-activated receptors.

Ginsenoside Rk1, one kind of ginsenoside, is a minor ginsenoside found in Panax ginseng and used as traditional Chinese medicine for centuries. It exhibits anti-tumor and anti-aggregation effects. However, little research has been done on its effect on endothelial function. This study investigated whether ginsenoside Rk1 improved endothelial dysfunction in diabetes and the underlying mechanisms in vivo and in vitro. Male C57BL/6 mice were fed with a 12 week high-fat diet (60% kcal % fat), whereas treatment groups were orally administered with ginsenoside Rk1 (10 and 20 mg per kg per day) in the last 4 weeks. Aortas isolated from C57BL/6 mice were induced by high glucose (HG; 30 mM) and co-treated with or without ginsenoside Rk1 (1 and 10 µM) for 48 h ex vivo. Moreover, primary rat aortic endothelial cells (RAECs) were cultured and stimulated by HG (44 mM) to mimic hyperglycemia, with or without the co-treatment of ginsenoside Rk1 (10 µM) for 48 h. Endothelium-dependent relaxations of mouse aortas were damaged with elevated oxidative stress and downregulation of three isoforms of peroxisome proliferator-activated receptors (PPARs), PPAR-α, PPAR-ß/δ, and PPAR-γ, as well as endothelial nitric oxide synthase (eNOS) phosphorylation due to HG or high-fat diet stimulation, which also existed in RAECs. However, after the treatment with ginsenoside Rk1, these impairments were all ameliorated significantly. Moreover, the vaso-protective and anti-oxidative effects of ginsenoside Rk1 were abolished by PPAR antagonists (GSK0660, GW9662 or GW6471). In conclusion, this study reveals that ginsenoside Rk1 ameliorates endothelial dysfunction and suppresses oxidative stress in diabetic vasculature through activating the PPAR/eNOS pathway.

LARP7 overexpression alleviates aortic senescence and atherosclerosis.

Atherosclerosis, characterized by the accumulation of lipid plaques on the inner walls of arteries, is the leading cause of heart attack, stroke and severe ischemic injuries. Senescent cells have been found to accumulate within atherosclerotic lesions and contribute to the progression of atherosclerosis. In our previous study, we discovered that suppressing Larp7 accelerates senescence by inhibiting Sirt1 activity, resulting in increased atherosclerosis in high-fat diet (HFD) fed and ApoE deficient (ApoEKO) mice. However, there has been no direct evidence demonstrating Larp7 per se could attenuate atherosclerosis. To this end, we generated a tetO-controlled and Cre-activated Larp7 gain-of-function mouse. Through RT-PCR and western blotting, we confirmed Larp7 overexpression in the aortas of HFD-fed ApoEKO; Larp7tetO mice. Larp7 overexpression led to increased Sirt1 activity and decreased cellular senescence signals mediated by p53/p65 in the aortas. Additionally, Larp7 overexpression reduced the presence of p16-positive senescent cells in the aortic lesions. Furthermore, Larp7 overexpression resulted in a decrease in pro-inflammatory macrophages and SASP factors. Consequently, Larp7 overexpression led to a reduction in the area of atherosclerotic lesions in HFD-fed ApoEKO; Larp7tetO mice. In summary, our study provides evidence that Larp7 overexpression holds promise as an approach to inhibit cellular senescence and prevent atherosclerosis.

SPAG5 deficiency activates autophagy to reduce atherosclerotic plaque formation in ApoE-/- mice.

BACKGROUND: Autophagy, as a regulator of cell survival, plays an important role in atherosclerosis (AS). Sperm associated antigen 5 (SPAG5) is closely associated with the classical autophagy pathway, PI3K/Akt/mTOR signaling pathway. This work attempted to investigate whether SPAG5 can affect AS development by regulating autophagy. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with oxidized-low density lipoprotein (ox-LDL) to induce cell damage. ApoE-/- mice were fed a Western diet to establish an AS mouse model. Haematoxylin and eosin (H&E) staining and Oil Red O staining evaluated the pathological changes and in lipid deposition in aortic tissues. CCK-8 and flow cytometry detected cell proliferation and apoptosis. Immunohistochemistry, Enzyme linked immunosorbent assay, qRT-PCR and western blotting assessed the levels of mRNA and proteins. RESULTS: Ox-LDL treatment elevated SPAG5 expression and the expression of autophagy-related proteins, LC3-I, LC3-II, Beclin-1, and p62, in HUVECs. GFP-LC3 dots were increased in ox-LDL-treated HUVECs and LPS-treated HUVECs. SPAG5 knockdown reversed both ox-LDL and LPS treatment-mediated inhibition of cell proliferation and promotion of apoptosis in HUVECs. SPAG5 silencing further elevated autophagy and repressed the expression of PI3K, p-Akt/Akt, and p-mTOR/mTOR in ox-LDL-treated HUVECs. 3-MA (autophagy inhibitor) treatment reversed SPAG5 silencing-mediated increase of cell proliferation and decrease of apoptosis in ox-LDL-treated HUVECs. In vivo, SPAG5 knockdown reduced atherosclerotic plaques in AS mice through activating autophagy and inhibiting PI3K/Akt/mTOR signaling pathway. CONCLUSION: This work demonstrated that SPAG5 knockdown alleviated AS development through activating autophagy. Thus, SPAG5 may be a potential target for AS therapy.