Aortic Area Research Articles

Cardiac MRI evaluation of aortic biophysical properties in paediatric Turner syndrome.

Aortopathy in Turner syndrome is associated with aortic dilation, and the risk of dissection is increased when the aortic size index is ≥ 2-2.5 cm/m2. We evaluated the aortic biophysical properties in paediatric Turner syndrome using cardiac MRI to determine their relationship to aortic size index. Turner syndrome patients underwent cardiac MRI to evaluate ventricular function, aortic dimensions, and biophysical properties (aortic stiffness index, compliance, distensibility, pulse wave velocity, and aortic and left ventricular elastance). Spearman correlation examined correlations between these properties and aortic size index. Data was compared to 10 controls. Of 25 Turner syndrome patients, median age 14.7 years (interquartile range: 11.0-16.8), height z score -2.7 (interquartile range: -2.92 - -1.54), 24% had a bicuspid aortic valve. Turner syndrome had increased diastolic blood pressure (p < 0.001) and decreased left ventricular end-diastolic (p < 0.001) and end-systolic (p = 0.002) volumes compared to controls. Median aortic size index was 1.81 cm/m2 (interquartile range: 1.45-2.1) and 7 had an aortic size index > 2 cm/m2. Aortic and left ventricular elastance were greater in Turner syndrome compared to controls (both p < 0.001). Increased aortic size index correlated with increased aortic elastance (r = 0.5, p = 0.01) and left ventricular elastance (r = 0.59, p = 0.002) but not aortic compliance. Higher ascending aortic areas were associated with increased aortic compliance (r = 0.44, p = 0.03) and left ventricular elastance (r = 0.49, p = 0.01). Paediatric Turner syndrome with similar aortic size index to controls showed MRI evidence of abnormal aortic biophysical properties. These findings point to an underlying aortopathy and provide additional parameters that may aid in determining risk factors for aortic dissection.

Marfan and Loeys-Dietz aortic phenotype: A potential tool for diagnosis and management

ObjectiveIn heritable aortic diseases, different vascular involvement may occur with potential variable implications in aortic dilation/dissection risk. This study aimed to analyze the aortic anatomy of individuals with Marfan syndrome and Loeys-Dietz syndrome to identify possible morphological differences. MethodsComputed tomography and magnetic resonance imaging of the thoracoabdominal aorta from the proximal supra-aortic vessels to the femoral bifurcation level of 114 patients with Marfan and Loeys-Dietz syndromes and 20 matched control subjects were examined. Aortic diameters, areas, length, and tortuosity were measured in different aortic segments using specific vessel analysis software. ResultsPatients with Marfan syndrome showed a higher prevalence of ascending aorta and aortic root dilation (P = .011), larger and longer aortic roots (P = .013) with pear-shaped phenotype, larger isthmus/descending aorta diameter ratio (P = .015), and larger suprarenal aorta and iliac arteries. Patients with Loeys-Dietz syndrome showed longer indexed segments and a significantly longer arch (P = .006) with type 2/3 arch prevalence (P = .097). Measurement ratios analysis provided cut-off values (aortic root to ascending aorta length/aortic root diameter, aortic root/sinotubular junction, aortic root/ascending aorta diameter) differentiating patients with Marfan syndrome from patients with Loeys-Dietz syndrome, even in the early stage of the disease. ConclusionsBoth syndromes show peculiar anatomic patterns at different aortic levels irrespective of aortic dilation and disease severity. These features may represent the expression of different genetic mutations on aortic development, with a potential impact on prognosis and possibly contributing to better management of the diseases. The systematic adoption of whole body imaging with magnetic resonance or computed tomography should always be considered, because they allow a complete vascular assessment with practical indicators of differential diagnosis.

Comparison of Left Ventricular Stroke Volume in 2nd- and 3rd-Trimester Fetuses Measured by the Product of VTI and Aortic Annular Area With That Assessed by Simpson's Single-Plane Rule Using the STE Technique.

The aim of the study was to compare left ventricle stroke volume in healthy, eutrophic fetuses in the 2nd and 3rd trimesters evaluated using the velocity time integral and aortic annulus area with left ventricular stroke volume measured using Simpson's single-plane rule and to determine the discrepancy equation. The study included 354 fetuses. In each fetus, during the same examination, simultaneous assessment of stroke volume was performed by pulsed-wave Doppler using the product of the velocity time integral and aortic annulus area and by the fetalHQ® software using Simpson's single-plane rule. The Mann-Whitney U test was used to compare the "product-derived" stroke volume and stroke volume using fetalHQ® software values in the 2nd and 3rd trimesters separately. The agreement between the two methods were verified using Bland-Altman analysis. A linear regression model was used to obtain the discrepancy equation. In the 2nd trimester, the mean percentage difference between both the techniques showed that the stroke volume values determined using pulsed-wave Doppler were, on average, 88% higher than the stroke volume values determined using fetalHQ®. The upper limit of agreement between the compared techniques was approximately 146% and the lower limit of agreement was equal to 29.6%. In the 3rd trimester, the results indicated that the stroke volume values determined using pulsed-wave Doppler were, on average, 76% higher than the stroke volume values determined using fetalHQ®. The upper limit of agreement between the compared techniques was approximately 129% and the lower limit of agreement was 23%. Based on the results of the linear regression models, discrepancy formulas of the stroke volume values were obtained. The equations to calculate the predicted mean and standard deviations were used to compute the reference intervals for the mean, 5th and 95th centiles. The calculation of left ventricular stroke volume using pulsed Doppler has higher result in relation to stroke volume determined using Simpson's rule significantly. The aortic annulus area showed a higher correlation regarding stroke volume than the velocity time integral in both the 2nd and 3rd trimesters. Stroke volume increased with the increase in aortic annulus area, whereas the velocity time integral remained relatively constant. The retrospective analysis of the collected material enabled the determination of the discrepancy equation.

A Case of Forming Test for the Diagnosis of PFO Combined Dynamic Left Ventricular Outflow Tract Stenosis after Occlusion

This patient was diagnosed with Patent Foramen Ovale (PFO) due to recurrent headaches, and her headaches improved significantly after oval foramen occlusion, but a grade 3/6 coarse murmur was heard in the aortic valve auscultation area, and left ventricular outflow tract stenosis was suggested by cardiac ultrasound. This change may be related to a variety of factors, suggesting that we should do a good preoperative assessment of the patient; intraoperative operation as gentle as possible to reduce the damage to the surrounding tissues; postoperative operation should be strengthened to avoid the progression of the inflammatory process, and at the same time to pay attention to the patient's symptoms, signs and dynamics of the relevant examinations to reduce the incidence of complications.

Morphological and dynamic analysis of the normal aortic valve with 4D computed tomography.

To evaluate the precise dimensions of the normal aortic root, especially the true aortic annulus, during the cardiac cycle using an innovative reconstruction method based on Multiphase Cardiac CT (MCCT) and to assess the feasibility and the reproducibility of this method for aortic root analysis. Between January 2019 and June 2021, 30 optimal consecutive ECG-gated MCCT of patients with normal tricuspid aortic valve were analyzed using an in-house software. Aortic annulus border was pinpointed on 9 reconstructed planes and the 3D coordinates of the 18 consecutive points were interpolated into a 3D curve using a cubic spline. Three additional planes were generated at the level of the left ventricular outflow tract, the level of the Valsalva sinus and the level of the sinotubular junction. This procedure was repeated for all the 10 temporal phases of the RR interval. The aortic annulus mean 3D and 2D areas were 7.67 ± 1.51 cm2 and 5.16 ± 1.40 cm2, respectively. Mean 2D diameter was 2.51 ± 0.23 cm. The mean global area expansion was 11.8 ± 3.5% and the mean perimeter expansion of 7.1 ± 2.6%. During the cardiac cycle, the left ventricle outflow tract expands, reaching its maximum surface at the end of diastole, followed by the aortic annulus, the valsalva sinuses and the sinotubular junction. The aorta changes from a clover shaped cone during diastole to more cylindrical shape during systole. Compared to the 3D measurements, the analysis of the virtual basal ring significantly underestimates the annulus area, perimeter, and mean diameter. 4D morphometric analysis enables to have a precise and reproducible evaluation of the aortic annulus. The aortic annulus and root are deformable structures that undergo a unique expansion sequence during the cardiac cycle which should be considered for procedural planning.

Successful Balloon-Expandable Transcatheter Aortic Valve Replacement for Extremely Large Annulus (>1,000 mm2)

Transcatheter aortic valve replacement in extra-large annulus is challenging because of the limited sizes and data of the current commercial prosthesis sizes available. We present a case of successful transcatheter aortic valve replacement with a new balloon-expandable SAPIEN 3 Ultra RESILIA valve for an aortic annulus area >1,000 mm2 on computed tomography.

Association Between Aortic Wall Parameters on Multidetector Computed Tomography and Ruptured Plaques By Nonobstructive General Angioscopy.

Nonobstructive general angioscopy (NOGA) can identify vulnerable plaques in the aortic lumen that serve as potential risk factors for cardiovascular events such as embolism. However, the association between computed tomography (CT) images and vulnerable plaques detected on NOGA remains unknown. We investigated 101 patients (67±11 years; women, 13.8%) who underwent NOGA and contrast-enhanced CT before or after 90 days in our hospital. On CT images, the aortic wall thickness, aortic wall area (AWA), and AWA in the vascular area were measured at the thickest point from the 6th to the 12th thoracic vertebral levels. Furthermore, the association between these measurements and the presence or absence of NOGA-derived aortic plaque ruptures (PRs) at the same vertebral level was assessed. NOGA detected aortic PRs in the aortic lumens at 145 (22.1%) of the 656 vertebral levels. The presence of PRs was significantly associated with greater aortic wall thickness (3.3±1.7 mm versus 2.1±1.2 mm), AWA (1.33±0.68 cm2 versus 0.89±0.49 cm2), and AWA in the vascular area (23.2%±9.3% versus 17.2%±7.6%) (P<0.001 for all) on the CT scans compared with the absence of PRs. The frequency of PRs significantly increased as the aortic wall thickness increased. Notably, a few NOGA-derived PRs were detected on CT in near-normal intima. The presence of NOGA-derived PRs was strongly associated with increased aortic wall thickness, AWA, and AWA in the vascular area, measured using CT. NOGA can detect PRs in the intima that appear almost normal on CT scans.

ZeXieYin formula alleviates atherosclerosis by inhibiting the MAPK/NF-κB signaling pathway in APOE−/− mice to attenuate vascular inflammation and increase plaque stability

Ethnopharmacological relevanceZexieyin formula (ZXYF), a traditional Chinese herbal formula recorded in the Huangdi Neijing to have efficacy in relieving spleen dampness and heat accumulation syndrome, which is also the key pathogenesis of atherosclerosis (AS). The efficacy has demonstrated by our previous studies. However, the intrinsic mechanism of ZXYF for treating vascular inflammation and the effect of inflammatory response on plaque are not known. Currently, plaque stabilization is crucial for the prognosis of AS. Aim of the studyOur study mainly focused on the therapeutic effects of ZXYF on high-fat diet (HFD)-induced vascular inflammation and vulnerable plaques (VP) in mice and explored its underlying mechanism. Methods and materialsMale apolipoprotein E knockout (APOE−/−) mice were fed HFD for 8 weeks to establish a VP model. During this period, the mice were also administered ZXYF, while atorvastatin (ATO) was used as a positive control. Aortic plaque area and morphology were detected by oil red staining and HE staining. Aortic plaque collagen content was detected by Masson staining. M1/M2 type macrophages were detected using immunofluorescence (IF). The study analyzed the levels of inflammation-related cytokines (IL-1β, IL-10, IL-6), MAPK/NF-κB pathway proteins, and NLRP3 inflammasomes (NLRP3, Caspase-1) using Western blot. Additionally, the levels of matrix metalloproteinase (MMP)-2 and MMP-9 and α-smooth muscle actin (α-SMA) in the aorta were analyzed using immunohistochemistry (IHC). The plaque instability index was calculated for each group using the vulnerable plaque formula. ResultsIn this study, APOE−/− mice were fed high-fat diet for 8 weeks. The results of oil-red and HE staining indicated a significant increase in the aortic plaque area of the mice, which exhibited a typical VP phenotype. ZXYF and ATO significantly improved AS plaques and prevented plaque rupture. HFD exacerbated vascular inflammation, stimulated macrophage conversion to M1-type through the MAPK/NF-κB signaling pathway, and released pro-inflammatory factors such as interleukin (IL)-1β, IL-1α, and IL-6. These factors activated NLRP3 inflammasome, leading to cellular death. However, ZXYF could reverse this trend and promote the conversion of macrophages to the anti-inflammatory M2 type. The anti-inflammatory effect of ATO was not significant. Moreover, HFD promoted the release of MMP-2 and MMP-9 from macrophages, which degraded plaque collagen, and induced a decrease in plaque SMC content, resulting in a thinning of the plaque fibrous cap. In contrast, ZXYF inhibited the decomposition of plaque collagen and increased the content of plaque smooth muscle cells (SMC) by reducing macrophage secretion of MMPs, thereby stabilizing plaques. Although ATO could reverse the decrease in plaque collagen and SMC content, its effect on MMPs was not significant. Finally, we calculated the vulnerability index to assess the overall risk of the plaque vulnerability phenotype. In line with these findings, ZXYF and ATO were able to effectively reverse the increase in the vulnerability index caused by HFD and lower the risk of adverse cardiovascular events. ConclusionOur results suggested that ZXYF could reduce inflammation and increase plaque stability by inhibiting the MAPK/NF-κB signaling pathway, which provided a theoretical basis for clinical application and subsequent research.

The influence of aortic stiffness on carotid stiffness: computational simulations using a human aorta carotid model.

Increased aortic and carotid stiffness are independent predictors of adverse cardiovascular events. Arterial stiffness is not uniform across the arterial tree and its accurate assessment is challenging. The complex interactions and influence of aortic stiffness on carotid stiffness have not been investigated. The aim of this study was to evaluate the effect of aortic stiffness on carotid stiffness under physiological pressure conditions. A realistic patient-specific geometry was used based on magnetic resonance images obtained from the OsiriX library. The luminal aortic-carotid model was reconstructed from magnetic resonance images using 3D Slicer. A series of aortic stiffness simulations were performed at different regional aortic areas (levels). By applying variable Young's modulus to the aortic wall under two pulse pressure conditions, one could examine the deformation, compliance and von Mises stress between the aorta and carotid arteries. An increase of Young's modulus in an aortic area resulted in a notable difference in the mechanical properties of the aortic tree. Regional deformation, compliance and von Mises stress changes across the aorta and carotid arteries were noted with an increase of the aortic Young's modulus. Our results indicate that increased carotid stiffness may be associated with increased aortic stiffness. Large-scale clinical validation is warranted to examine the influence of aortic stiffness on carotid stiffness.

Inducing aortic aneurysm/dissection in zebrafish: evaluating the efficacy of β-Aminopropionic Nitrile as a model

ABSTRACT Aortic aneurysm/dissection (AAD) poses a life-threatening cardiovascular emergency with complex mechanisms and a notably high mortality rate. Zebrafish (Danio rerio) serve as valuable models for AAD due to the conservation of their three-layered arterial structure and genome with that of humans. However, the existing studies have predominantly focused on larval zebrafish, leaving a gap in our understanding of adult zebrafish. In this study, we utilized β-Aminopropionic Nitrile (BAPN) impregnation to induce AAD in both larval and adult zebrafish. Following induction, larval zebrafish exhibited a 28% widening of the dorsal aortic diameter (p < 0.0004, n = 10) and aortic arch malformations, with a high malformation rate of 75% (6/8). Conversely, adult zebrafish showed a 41.67% (5/12) mortality rate 22 days post-induction. At this time point, the dorsal aortic area had expanded by 2.46 times (p < 0.009), and the vessel wall demonstrated significant thickening (8.22 ± 2.23 μM vs. 26.38 ± 10.74 μM, p < 0.05). Pathological analysis revealed disruptions in the smooth muscle layer, contributing to a 58.33% aneurysm rate. Moreover, the expression levels of acta2, tagln, cnn1a, and cnn1b were decreased, indicating a weakened contractile phenotype. Transcriptome sequencing showed a significant overlap between the molecular features of zebrafish tissues post-BAPN treatment and those of AAD patients. Our findings present a straightforward and practical method for generating AAD models in both larval and adult zebrafish using BAPN.

Early results of transcatheter electrosurgical aortic septotomy for endovascular repair of chronic dissecting aortoiliac aneurysms

ObjectiveEndovascular repair of chronic dissecting aortoiliac aneurysms is challenging given the rigid septum, compressed true lumen (TL), and target vessels frequently originating in the false lumen. We have used transcatheter electrosurgical aortic septotomy (TEAS) before stent graft implantation under intravascular ultrasound (IVUS) and fusion guidance. The purpose of this study is to assess the outcomes of TEAS during complex endovascular repair of dissecting aneurysms. MethodsFrom 2021 to 2023, 17 patients underwent TEAS. The primary end point was technical success, with secondary end points of proximal and distal seals, target vessel instability, aortic and iliac TL and cross-sectional area (CSA) expansion, and aortic-related death. During the procedure, the aortic septum is crossed through a pre-existing entry or via electrocautery-activated 0.018-in. Astato XS20 wire (Asahi-Intecc) under IVUS and fusion guidance. The penetrated wire is then snared in the false lumen and pulled through the ipsilateral femoral access. A 1-cm length of the middle of the Astato wire coating is kinked in a three-sided polygonal configuration, denuded the inner surface of the wire using a no. 15 blade, and positioned at the apex of the septum. Both ends of the Astato wire are insulated with 0.018-in. microcatheters, and the back end of the wire is denuded and connected to cautery. Gentle traction is applied to the wire, and short bursts of electrocautery cutting are applied at 60 to 80 W. ResultsThe technical success of the septotomy was 100%. No incidence of visceral or lower extremity malperfusion, vascular injury, or distal embolization occurred. Of the 17 patients, 4 underwent thoracic endovascular aneurysm repair, 2 underwent endovascular aortic repair, and 11 underwent fenestrated/branched endovascular aneurysm repair after septotomy. All target vessels were successfully stented. A distal landing zone seal with exclusion of the false lumen was achieved in 16 of the 17 patients (94.1%). One patient required embolization of the false lumen of the celiac artery after septotomy. The TL mean diameter and CSA of the descending thoracic aorta after septotomy was expanded by 7.01 ± 1.9 mm (relative mean diameter expansion, 42.3%; P < .0001) and 2.71 ± 0.4 cm2 (relative mean CSA expansion, 57.3%, P<.0001). For patients who required septotomy through the common iliac arteries, the mean TL was expanded by 8.1 ± 3.7 mm (relative mean diameter expansion, 76%; P < .0001) and 1.76 ± 0.91 cm2 (relative mean CSA expansion, 209%; P < .0001). The 1-year freedom from target vessel instability was 91%. ConclusionsThe use of IVUS and fusion-guided TEAS offers a promising technique to facilitate TL expansion and false lumen exclusion in chronic dissecting aortic aneurysms before repair. The durability and long-term outcomes of this technique in a larger cohort remain to be elucidated.

Type A Aortic Dissection: A Call for Vigilance in Chest Pain Diagnosis

Introduction: Acute aortic dissection (AD) is a rare and life-threatening condition associated with high mortality rates in the absence of prompt intervention. This article provides an in-depth examination of the clinical presentation, diagnostic approach, and management of Stanford type A AD in a 62-year-old hypertensive female patient with atypical symptoms.&#x0D; Case Report: The patient presented with retrosternal chest pain and rapidly worsening dyspnea, demonstrating a 3/6 diastolic murmur over the aortic area. Diagnostic findings included negative T-waves on ECG, significant mediastinal widening on chest X-ray, and transthoracic echocardiography revealing an intimal flap, ascending aorta dilation, and acute aortic insufficiency. Computed tomography confirmed a Stanford type A aortic dissection.&#x0D; Discussion: Acute AD poses a diagnostic challenge, as atypical presentations can lead to misdiagnoses. The case emphasizes the importance of considering AD in the differential diagnosis of chest pain and conducting thorough investigations, especially when faced with unusual symptoms. Management strategies, encompassing both pharmacological and surgical interventions, are crucial for addressing AD promptly.&#x0D; Conclusion: This case underscores the significance of recognizing both typical and atypical presentations of AD to ensure timely intervention and avoid potentially catastrophic outcomes. A comprehensive understanding of diagnostic approaches and management protocols is essential in the emergency setting. Overall, this article contributes to the growing body of knowledge surrounding acute aortic dissection and emphasizes the critical need for awareness and rapid intervention in clinical practice.

Infective Endocarditis Induced – Decompensation of Chronic Liver Disease Presenting as Hepatic Encephalopathy

Abstract Infective endocarditis (IE) occurs in people of older age, with artificial or damaged heart valves, immunocompromised states, and intravenous (IV) drug abusers as major risk factors. This case report describes a rare presentation of IE in a patient with chronic liver disease (CLD). A 38-year-old female with a history of decompensated CLD due to hepatitis C, presented with high-grade fever with chills, abdominal pain, shortness of breath, melena, and altered mental status. On examination, she had signs of hepatic encephalopathy and a systolic murmur in the aortic area. Imaging studies revealed an aortic valve vegetation with moderate aortic regurgitation, and blood cultures were negative. Treatment with meropenem and teicoplanin was started which resulted in clinical improvement. This case highlights the importance of considering IE in patients with CLD presenting with decompensation and suggests that early diagnosis and treatment are crucial in improving outcomes.

Photon-counting CT-angiography in pre-TAVR aortic annulus assessment: effects of retrospective vs. prospective ECG-synchronization on prosthesis valve selection

To compare the diagnostic value of ultrahigh-resolution CT-angiography (UHR-CTA) compared with high-pitch spiral CTA (HPS-CTA) using a first-generation, dual-source photon-counting CT (PCD-CT) scanner for preprocedural planning of transcatheter aortic valve replacement (TAVR). Clinically referred patients with severe aortic valve stenosis underwent both, retrospective ECG-gated cardiac UHR-CTA (collimation: 120 × 0.2 mm) and prospective ECG-triggered aortoiliac HPS-CTA (collimation: 144 × 0.4 mm, full spectral capabilities) for TAVR planning from August 2022 to March 2023. Radiation dose was extracted from the CT reports, and the effective dose was calculated. Two radiologists analyzed UHR-CTA and HPS-CTA datasets, assessing the image quality of the aortic annulus, with regard to the lumen visibility and margin delineation using a 4-point visual-grading scale (ranges: 4 = ”excellent” to 1 = ”poor”). Aortic annulus area (AAA) measurements were taken for valve prosthesis sizing, with retrospective UHR-CTA serving as reference standard. A total of 64 patients were included (mean age, 81 years ± 7 SD; 28 women) in this retrospective study. HPS-CTA showed a lower radiation dose, 4.1 mSv vs. 12.6 mSv (p < 0.001). UHR-CTA demonstrated higher image quality to HPS-CTA (median score, 4 [IQR, 3–4] vs. 3 [IQR, 2–3]; p < 0.001). Quantitative assessments of AAA from both CTA datasets were strongly positively correlated (mean 477.4 ± 91.1 mm2 on UHR-CTA and mean 476.5 ± 90.4 mm2 on HPS-CTA, Pearson r2 = 0.857, p < 0.001) with a mean error of 22.3 ± 24.6 mm2 and resulted in identical valve prosthesis sizing in the majority of patients (91%). Patients with lower image quality on HPS-CTA (score value 1 or 2, n = 28) were more likely to receive different sizing recommendations (82%). Both UHR-CTA and HPS-CTA acquisitions using photon-counting CT technology provided reliable aortic annular assessments for TAVR planning. While UHR-CTA offers superior image quality, HPS-CTA is associated with lower radiation exposure. However, severely impaired image quality on HPS-CTA may impact on prosthesis sizing, suggesting that immediate post-scan image evaluations may require complementary UHR-CTA scanning.

Mussel oil is superior to fish oil in preventing atherosclerosis of ApoE-/- mice.

The present study aimed to explore the preventive effect of mussel oil (MO) on atherosclerosis and the potential mechanism in apolipoprotein E-null (ApoE-/-) mice. ApoE-/- mice were fed with a high-fat and high-cholesterol chow and given corn oil (CO), fish oil (FO), MO, or aspirin (ASP, dissolved in CO) by gavage for 12 weeks. The total n-3 polyunsaturated fatty acids (PUFAs) in MO (51.01%) and FO (46.82%) were comparable (mainly C22:6n-3 and C20:5n-3). Wild-type mice were fed with a normal chow and given equivalent CO as health control (CON). Compared with the CON group, obvious atherosclerotic plaque appeared at aorta and aortic sinus in the CO group. Compared with the CO group, MO but not FO had a significantly smaller atherosclerotic plaque area in the aorta. The aortic atherosclerotic plaque area was comparable in the MO, CON, and ASP groups. The MO group had a significantly smaller atherosclerotic plaque area, lower lipid deposition, lower contents of smooth muscle cell (SMC), and slightly lower contents of macrophage at the aortic sinus than the FO group. Serum concentrations of IL-1β, NF-κB, and VCAM-1 were comparable in the MO and FO groups and were significantly lower than the CO group. Compared with the CO group, the MO group but not FO group had significantly lower aortic protein levels of p65NF-κB, p38MAPK, and VCAM-1. The aortic protein levels of p-p65NF-κB and p-p38MAPK were significantly lower in the MO group than the FO group. In conclusion, MO is more potent than FO in preventing atherosclerosis, and the possible mechanism may be by downregulating p38MAPK/NF-κB signaling pathway, decreasing VCAM-1 and macrophage, and inhibiting proliferation and migration of SMC.

Low-Shear Stress Promotes Atherosclerosis via Inducing Endothelial Cell Pyroptosis Mediated by IKKε/STAT1/NLRP3 Pathway

Atherosclerosis is initiated by vascular endothelial dysfunction, and low-shear stress (LSS) of blood flow is a key factor leading to endothelial dysfunction. Growing evidence suggests that endothelial cell pyroptosis plays an important role in the development of atherosclerosis. Studies have shown that low-shear stress can induce endothelial cell pyroptosis, but the exact mechanism remains unclear. Our experiments demonstrated that low-shear stress induced endothelial cell pyroptosis and the phosphorylation of IκB kinase ε (IKKε). IKKε knockdown not only significantly attenuated atherosclerosis lesions of aortic arch areas in ApoE−/− mice fed with high cholesterol diets, but also markedly reduced endothelial cell pyroptosis and NLRP3 expression triggered by low-shear stress. Further mechanism studies showed that IKKε promoted the expression of NLRP3 via activating signal transducer and activator of transcription 1 (STAT1) and the subsequent binding of STAT1 to NLRP3 promoter region. These results suggest that low-shear stress plays a pro-atherosclerotic role by promoting endothelial cell pyroptosis through the IKKε/STAT1/NLRP3 pathway, which provides new insights into the formation of atherosclerosis.

Genetic association of lipid-lowering drugs with aortic aneurysms: a Mendelian randomization study.

The lack of effective pharmacotherapies for aortic aneurysms (AA) is a persistent clinical challenge. Lipid metabolism plays an essential role in AA. However, the impact of lipid-lowering drugs on AA remains controversial. The study aimed to investigate the genetic association between lipid-lowering drugs and AA. Our research used publicly available data on genome-wide association studies (GWASs) and expression quantitative trait loci (eQTL) studies. Genetic instruments, specifically eQTLs related to drug-target genes and SNPs (single nucleotide polymorphisms) located near or within the drug-target loci associated with low-density lipoprotein cholesterol (LDL-C), have been served as proxies for lipid-lowering medications. Drug-Target Mendelian Randomization (MR) study is used to determine the causal association between lipid-lowering drugs and different types of AA. The MR analysis revealed that higher expression of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) was associated with increased risk of AA (OR = 1.58, 95% CI = 1.20-2.09, P = 1.20 × 10-03) and larger lumen size (aortic maximum area: OR = 1.28, 95% CI = 1.13-1.46, P = 1.48 × 10-04; aortic minimum area: OR = 1.26, 95% CI = 1.21-1.42, P = 1.78 × 10-04). PCSK9 (proprotein convertase subtilisin/kexin type 9) and CETP (cholesteryl ester transfer protein) show a suggestive relationship with AA (PCSK9: OR = 1.34, 95% CI = 1.10-1.63, P = 3.07 × 10-03; CETP: OR = 1.38, 95% CI = 1.06-1.80, P = 1.47 × 10-02). No evidence to support genetically mediated NPC1L1 (Niemann-Pick C1-Like 1) and LDLR (low-density lipoprotein cholesterol receptor) are associated with AA. This study provides causal evidence for the genetic association between lipid-lowering drugs and AA. Higher gene expression of HMGCR, PCSK9, and CETP increases AA risk. Furthermore, HMGCR inhibitors may link with smaller aortic lumen size.

Zexieyin formula alleviates atherosclerosis with cognitive impairment: A novel role in the treatment of comorbidities and its underlying mechanisms

Ethnopharmacological relevancyZexieyin formula (ZXYF) has been identified to have therapeutic actions of atherosclerosis (AS). It's unknown that whether ZXYF has therapeutic potential of atherosclerosis (AS) with cognitive impairment (CI) and its underlying mechanisms. Aim of the studyTo elucidate therapeutic effect of ZXYF for AS with CI as well as its underlying mechanisms in AS with CI mice model. Methods and materialsTo establish AS with CI model, we fed ApoE−/− mice with high-fat diet (HFD) for 8 weeks. Oil red O staining (ORO) and Hematoxylin-eosin staining (HE) were used to detect aortic plaque area. Morris water maze (MWM) and Y-maze were used to measure cognitive function and cognitive improvement after administration of ZXYF and atorvastatin (ATO). Network pharmacology was used to screen for potential mechanisms for improving cognitive function. Western blot was used to detect expressions of MAPK, Aβ and synaptic proteins in hippocampus. ResultsHFD caused and accelerated the AS in ApoE−/− mice, while it was easier able to produce CI than normal mice. Administration of ZXYF or ATO for 8 weeks significantly reduced aortic plaque area in ORO and HE tests, and improved cognitive abilities in MWM and Y-maze tests. Network pharmacology results showed that MAPK or synaptic proteins were highly associated with CI. HFD contributed to abnormal expressions of MAPK (pERK, pP38, pJNK), NF-kB, synaptic proteins (PSD95, synapsin1) and β-amyloid (Aβ) in hippocampus, which were all reversed by ZXYF. However, ERK and PSD95 expressions were not reversed by ATO in hippocampus. ConclusionsZXYF mitigated AS, further alleviating CI by modulating MAPK signaling, relating to synaptic proteins enhancing and Aβ protein decreasing in the hippocampus. This study firstly lit up the new clinical application of ZXYF, which might promote the use of ZXYF in AS and CI patients.

Echocardiographic parameters associated with less reverse left ventricular remodeling after transcatheter aortic valve implant in subjects with prosthesis patient mismatch.

Transaortic valve implant (TAVI) is the treatment of choice for severe aortic stenosis (AS). Some patients develop prosthesis patient mismatch (PPM) after TAVI. It is challenging to determine which patients are at risk for clinical deterioration. We retrospectively measured echocardiographic parameters of left ventricular (LV) morphology and function, prosthetic aortic valve effective orifice area (iEOA) and hemodynamics in 313 patients before and 1year after TAVI. Our objective was to compare the change in echocardiographic parameters associated with left ventricular reverse modeling in subjects with and without PPM. Our secondary objective was to evaluate echo parameters associated with PPM and the relationship to patient functional status and survival post-TAVI. We found that 82 (26.2%) of subjects had moderate and 37 (11.8%) had severe PPM post-TAVI. There was less relative improvement in LVEF with PPM (1.9±21.3% vs. 8.2+30.1%, p=.045). LV GLS also exhibited less relative improvement in those with PPM (13.4+34.1% vs. 30.9+73.3%, p=.012). NYHA functional class improved in 84.3% of subjects by one grade or more. Echocardiographic markers of PPM were worse in those without improvement in NYHA class (mean AT/ET was .29 vs. .27, p=.05; DVI was .46 vs. .51, p=.021; and iEOA was .8cm/m2 vs. .9cm/m2 , p=.025). There was no association with PPM and survival. There was no improvement in LVEF and less improvement in LV GLS in those with PPM post-TAVI. Echocardiographic markers of PPM were present in those with lack of improvement in NYHA functional class.

Mitochondrial dysfunction and metabolic reprogramming induce macrophage pro-inflammatory phenotype switch and atherosclerosis progression in aging.

Aging increases the risk of atherosclerotic vascular disease and its complications. Macrophages are pivotal in the pathogenesis of vascular aging, driving inflammation and atherosclerosis progression. NOX4 (NADPH oxidase 4) expression increases with age, correlating with mitochondrial dysfunction, inflammation, and atherosclerosis. We hypothesized that the NOX4-dependent mitochondrial oxidative stress promotes aging-associated atherosclerosis progression by causing metabolic dysfunction and inflammatory phenotype switch in macrophages. We studied atherosclerotic lesion morphology and macrophage phenotype in young (5-month-old) and aged (16-month-old) Nox4 -/-/Apoe -/- and Apoe -/- mice fed Western diet. Young Nox4-/-/Apoe-/- and Apoe-/- mice had comparable aortic and brachiocephalic artery atherosclerotic lesion cross-sectional areas. Aged mice showed significantly increased lesion area compared with young mice. Aged Nox4-/-/Apoe-/- had significantly lower lesion areas than Apoe-/- mice. Compared with Apoe-/- mice, atherosclerotic lesions in aged Nox4-/-/Apoe-/- showed reduced cellular and mitochondrial ROS and oxidative DNA damage, lower necrotic core area, higher collagen content, and decreased inflammatory cytokine expression. Immunofluorescence and flow cytometry analysis revealed that aged Apoe-/- mice had a higher percentage of classically activated pro-inflammatory macrophages (CD38+CD80+) in the lesions. Aged Nox4-/-/Apoe-/- mice had a significantly higher proportion of alternatively activated pro-resolving macrophages (EGR2+/CD163+CD206+) in the lesions, with an increased CD38+/EGR2+ cell ratio compared with Apoe-/- mice. Mitochondrial respiration assessment revealed impaired oxidative phosphorylation and increased glycolytic ATP production in macrophages from aged Apoe-/- mice. In contrast, macrophages from Nox4-/-/Apoe-/- mice were less glycolytic and more aerobic, with preserved basal and maximal respiration and mitochondrial ATP production. Macrophages from Nox4-/-/Apoe-/- mice also had lower mitochondrial ROS levels and reduced IL1β secretion; flow cytometry analysis showed fewer CD38+ cells after IFNγ+LPS treatment and more EGR2+ cells after IL4 treatment than in Apoe-/- macrophages. In aged Apoe-/- mice, inhibition of NOX4 activity using GKT137831 significantly reduced macrophage mitochondrial ROS and improved mitochondrial function, resulting in decreased CD68+CD80+ and increased CD163+CD206+ lesion macrophage proportion and attenuated atherosclerosis. Our findings suggest that increased NOX4 in aging drives macrophage mitochondrial dysfunction, glycolytic metabolic switch, and pro-inflammatory phenotype, advancing atherosclerosis. Inhibiting NOX4 or mitochondrial dysfunction could alleviate vascular inflammation and atherosclerosis, preserving plaque integrity.