Nesfatin-1 enhances vascular smooth muscle calcification through facilitating BMP-2 osteogenic signaling.

Vascular calcification (VC) arises from the accumulation of calcium salts in the intimal or tunica media layer of the aorta, contributing to higher risk of cardiovascular events and mortality. Despite this, the mechanisms driving VC remain incompletely understood. We previously described that nesfatin-1 functioned as a switch for vascular smooth muscle cells (VSMCs) plasticity in hypertension and neointimal hyperplasia. In this study, we sought to investigate the role and mechanism of nesfatin-1 in VC. The expression of nesfatin-1 was measured in calcified VSMCs and aortas, as well as in patients. Loss- and gain-of-function experiments were evaluated the roles of nesfatin-1 in VC pathogenesis. The transcription activation of nesfatin-1 was detected using a mass spectrometry. We found higher levels of nesfatin-1 in both calcified VSMCs and aortas, as well as in patients with coronary calcification. Loss-of-function and gain-of-function experiments revealed that nesfatin-1 was a key regulator of VC by facilitating the osteogenic transformation of VSMCs. Mechanistically, nesfatin-1 promoted the de-ubiquitination and stability of BMP-2 via inhibiting the E3 ligase SYTL4, and the interaction of nesfatin-1 with BMP-2 potentiated BMP-2 signaling and induced phosphorylation of Smad, followed by HDAC4 phosphorylation and nuclear exclusion. The dissociation of HDAC4 from RUNX2 elicited RUNX2 acetylation and subsequent nuclear translocation, leading to the transcription upregulation of OPN, a critical player in VC. From a small library of natural compounds, we identified that Curculigoside and Chebulagic acid reduced VC development via binding to and inhibiting nesfatin-1. Eventually, we designed a mass spectrometry-based DNA-protein interaction screening to identify that STAT3 mediated the transcription activation of nesfatin-1 in the context of VC. Overall, our study demonstrates that nesfatin-1 enhances BMP-2 signaling by inhibiting the E3 ligase SYTL4, thereby stabilizing BMP-2 and facilitating the downstream phosphorylation of SMAD1/5/9 and HDAC4. This signaling cascade leads to RUNX2 activation and the transcriptional upregulation of MSX2, driving VC. These insights position nesfatin-1 as a potential therapeutic target for preventing or treating VC, advancing our understanding of the molecular mechanisms underlying this critical cardiovascular condition.

The Effect of Number of Pregnancies on Aortic Stiffness Index, Aortic Velocity Propagation, and Epicardial Fat Thickness.

OBJECTIVE: Pregnancy causes physiological, hormonal, and hemodynamic changes that affect the aortic wall dimensions and elastic properties. Multiple pregnancies increase the risk of aortic enlargement and reduce aortic elasticity. The aortic stiffness index (ASI) and aortic velocity propagation (AVP) are markers of elasticity. Additionally, epicardial fat thickness (EFT) is associated with cardiovascular risk factors. The impact of multiparity on ASI, AVP, and EFT has not been previously reported in the literature. Therefore, we aimed to investigate the association of these parameters with the number of live pregnancies in this study. METHODS: A total of 410 patients were enrolled in this prospective study. Patients were divided into three groups based on the number of live births: Group 1 (n = 0, 128 patients), Group 2 (4 ≥ n > 0, 157 patients), and Group 3 (n ≥ 5, 125 patients). A linear regression analysis was conducted to investigate trend associations of ASI, AVP, and EFT between the study groups. Multiple linear regression analysis was used to evaluate the independent predictors of continuous parameters. RESULTS: There were increasing trends in multiparity with variables such as aortic systolic (ASD) and diastolic diameters, pulmonary artery diameters, ASI, and EFT, and a decreasing trend in AVP. The number of pregnancies was strongly and positively correlated with ASI, moderately and positively correlated with EFT and ASD, and moderately and negatively correlated with AVP. CONCLUSION: Multiparity was independently associated with ASI, EFT, ASD, and AVP, reflecting decreased elasticity and elevated cardiovascular risk in multiparous women.

Prolonged Copper Supplementation Modified Minerals in the Kidney, Liver and Blood, and Potentiated Oxidative Stress and Vasodilation of Isolated Aortic Rings in Young Wistar Rats.

BACKGROUND: Previous studies have highlighted that copper supplementation at 200% of the recommended daily dietary allowance modified vascular contraction and relaxation through increased reactive oxygen species (ROS) and prostaglandin formation, which modified the antioxidant status of middle-aged Wistar rats. METHODS: In this study, young (1 month old) male Wistar rats (n/group = 10) received a diet supplemented with 6.45 mg copper/kg (100% of daily recommendation-Group A) for 8 weeks. The experimental group received 12.9 mg copper/kg of diet (200% of the daily recommendation-Group B). RESULTS: Experimental supplementation with 200% copper modified the copper concentration in the blood (1.21-fold, p = 0.04), liver (1.15-fold, p = 0.032), and kidneys (1.23-fold, p = 0.045), potentiated the ROS formation in the aortic rings, and enhanced the sensitivity of the aortic rings to the vasodilator acetylcholine. We observed an increased participation of nitric oxide (NO) derived from inducible NO synthase (iNOS) in vascular contraction and a decreased net effect of vasodilator prostanoids derived from cyclooxygenase-2 in vascular relaxation. In rat kidneys, the concentrations of potassium (1.08-fold, p = 0.001) and iron (1.13-fold, p = 0.046) were higher, while, calcium (0.88-fold, p = 0.001) and chromium (0.77-fold, p = 0.005) concentrations were lower. In the rat liver, magnesium (1.06-fold, p = 0.012) was higher. No differences were observed in the concentrations of sodium, zinc, manganese, selenium, cobalt, molybdenum, and vanadium. The antioxidant activity of water- and lipid-soluble compounds; total antioxidant status in the blood; and superoxide dismutase, catalase, and malondialdehyde levels in the heart did not change. CONCLUSIONS: In young rats, prolonged supplementation with 200% copper had a lesser effect than anticipated on oxidative stress and vascular reactivity. Detailed data on the status of trace elements and their interactions in patients of different age groups are strongly required for effective nutritional and therapeutic intervention.

Para-aortic and pelvic lymphadenectomy in locally advanced cervical cancer with pelvic lymph node metastasis.

OBJECTIVE: This study sought to explore the efficiency of para-aortic and pelvic lymphadenectomy in the treatment of locally advanced cervical cancer (LACC) with pelvic lymph node (PLN) metastasis. METHODS: A total of 171 LACC patients with imaging-confirmed pelvic lymph node metastasis were included in this study. These patients were divided into two groups: the surgical staging group, comprising 58 patients who had received para-aortic and pelvic lymphadenectomy (surgical staging) along with concurrent chemoradiation therapy (CCRT), and the imaging staging group, comprising 113 patients who had received only CCRT. The two groups' progression-free survival (PFS), overall survival (OS) and treatment-related complications were compared. RESULTS: The surgical staging group started radiotherapy 10.2 days (range 9-12 days) later than the imaging staging group. The overall incidence of lymphatic cysts was 9.30%. In the surgical staging group, para-aortic lymph node metastasis was identified in 34.48% (20/58) of patients, while pathology-negative PLN was observed in 12.07% (7/58). Over a median follow-up period of 52 months, no significant differences in PFS and OS rates were found between the two groups (p > 0.05). Subgroup analysis of patients with lymph node diameters of ≥ 1.5 cm revealed a five-year PFS rate of 75.0% and an OS rate of 80.0% in the surgical staging group, compared to 41.5% and 50.1% in the imaging staging group, respectively, showing statistically significant differences (p = 0.022, HR:0.34 [0.13, 0.90] and p = 0.038, HR: 0.34 [0.12,0.94], respectively for PFS and OS). Additionally, in patients with two or more metastatic lymph nodes, the five-year PFS and OS rates were 69.2% and 73.1% in the surgical staging group, versus 41.0% and 48.4% in the imaging staging group, with these differences also being statistically significant (p = 0.025, HR: 0.41[0.19,0.93] and p = 0.046, HR: 0.42[0.18,0.98], respectively). CONCLUSION: Performing surgical staging before CCRT is safe and delivers accurate lymph node details crucial for tailoring radiotherapy. This approach merits further investigation, particularly in women with pelvic lymph nodes measuring 1.5 cm or more in diameter or patients with two or more imaging-positive PLNs.

Inhibition of poly(ADP-Ribosyl)ation reduced vascular smooth muscle cells loss and improves aortic disease in a mouse model of human accelerated aging syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder associated with features of accelerated aging. HGPS is an autosomal dominant disease caused by a de novo mutation of LMNA gene, encoding A-type lamins, resulting in the truncated form of pre-lamin A called progerin. While asymptomatic at birth, patients develop symptoms within the first year of life when they begin to display accelerated aging and suffer from growth retardation, and severe cardiovascular complications including loss of vascular smooth muscle cells (VSMCs). Recent works reported the loss of VSMCs as a major factor triggering atherosclerosis in HGPS. Here, we investigated the mechanisms by which progerin expression leads to massive VSMCs loss. Using aorta tissue and primary cultures of murine VSMCs from a mouse model of HGPS, we showed increased VSMCs death associated with increased poly(ADP-Ribosyl)ation. Poly(ADP-Ribosyl)ation is recognized as a post-translational protein modification that coordinates the repair at DNA damage sites. Poly-ADP-ribose polymerase (PARP) catalyzes protein poly(ADP-Ribosyl)ation by utilizing nicotinamide adenine dinucleotide (NAD+). Our results provided the first demonstration linking progerin accumulation, augmented poly(ADP-Ribosyl)ation and decreased nicotinamide adenine dinucleotide (NAD+) level in VSMCs. Using high-throughput screening on VSMCs differentiated from iPSCs from HGPS patients, we identified a new compound, trifluridine able to increase NAD+ levels through decrease of PARP-1 activity. Lastly, we demonstrate that trifluridine treatment in vivo was able to alleviate aortic VSMCs loss and clinical sign of progeria, suggesting a novel therapeutic approach of cardiovascular disease in progeria.

Effect of aortic valve phenotype and sex on aorta dilation in patients with aortic stenosis.

BACKGROUND: Bicuspid aortic valve (BAV) is often associated with a concomitant aortopathy. However, few studies have evaluated the effect of the aortic valve (AV) phenotype on the rate of dilation of the aorta. This study aimed to compare the progression rate of aorta dimensions according to AV phenotype (BAV vs tricuspid AV (TAV)), fusion type and sex in patients with aortic stenosis (AS). METHODS: 310 patients with AS (224 TAV and 86 BAV) recruited in the Metabolic Determinants of the Progression of Aortic Stenosis study (PROGRESSA, NCT01679431) were included in this analysis. Doppler echocardiography was performed annually to assess AS severity and measure ascending aorta (AA) dimensions. Baseline and last follow-up visit measurements were used to assess the annualised change. RESULTS: Median AA annualised change was larger in BAV versus TAV (0.33±0.65 mm/year vs 0.21±0.56 mm/year, p=0.04). In the whole cohort, BAV phenotype and higher low-density lipoprotein (LDL) levels were significantly associated with fast progression of AA dilation in univariate analysis (OR 1.80, 95% CI 1.08 to 2.98, p=0.02; 1.37, 95% CI 1.04 to 1.80, p=0.03, respectively). AA dilation rate did not vary according to the BAV subtype (p=0.142). Predictors of AA progression rate were different between valve phenotypes, with higher apolipoprotein B/apolipoprotein A-I ratio, higher baseline peak aortic jet velocity (Vpeak) and smaller baseline AA diameter in the TAV cohort (all p<0.05) versus absence of hypertension, higher LDL levels and smaller baseline AA diameter in the BAV cohort (all p<0.02). In men, higher baseline Vpeak and smaller baseline AA (p<0.001) were independently associated with increased annualised AA dilation, while in women, higher LDL levels (p=0.026) were independently associated with faster AA dilation. CONCLUSION: This study suggests that BAV is associated with faster dilation of the AA. Predictors of AA dilation are different between valve phenotype and sex, with higher LDL levels being associated with faster AA dilation in BAV.

Role of macrophages in aortic dissection pathogenesis: insights from preclinical studies to translational prospective.

Aortic dissection is a critical vascular disease that is characterized by a high mortality rate and inflammation significantly influences its onset and progression. Recent studies highlight the integral role of macrophages, key players in the immune system, in the pathological landscape of aortic dissection. These cells are involved in crucial processes, such as the remodeling of the extracellular matrix, immunocyte infiltration, and phenotypic switching of smooth muscle cells, which are essential for the structural integrity and functional dynamics of the aortic wall. Despite these insights, the specific contributions of macrophages to the development and progression of aortic dissection remains unclear. This review explores the pathogenesis of aortic dissection with a focus on macrophages and describes their origins, phenotypic variations, and potential roles based on the most recent research findings. Furthermore, we discuss key molecules related to macrophages during aortic dissection, their interactions with other cellular components within the aorta, and the implications of these interactions for future therapeutic strategies. This comprehensive analysis aimed to improve our understanding of macrophages in aortic dissection and promote the development of targeted interventions.

3D-printing hydrogel programmed released exosomes to restore aortic medial degeneration through inhibiting VSMC ferroptosis in aortic dissection.

Aortic dissection (AD) is a devastating disease with a high mortality rate. Exosomes derived from mesenchymal stem cells (exo-MSCs) offer a promising strategy to restore aortic medial degeneration and combat ferroptosis in AD. However, their rapid degradation in the circulatory system and low treatment efficiency limit their clinical application. Methylacrylated gelatin (Gelma) was reported as a matrix material to achieve controlled release of exosomes. Herein, exo-MSCs-embedded in Gelma hydrogels (Gelma-exos) using ultraviolet light and three-dimensional (3D) printing technology. These Gelma-exos provide a sustained release of exo-MSCs as Gelma gradually degrades, helping to restore aortic medial degeneration and prevent ferroptosis. The sustained release of exosomes can inhibit the phenotypic switch of vascular smooth muscle cells (VSMCs) to a proliferative state, and curb their proliferation and migration. Additionally, the 3D-printed Gelma-exos demonstrated the ability to inhibit ferroptosis in vitro, in vivo and ex vivo experiments. In conclusion, our Gelma-exos, combined with 3D-printed technology, offer an alternative treatment approach for repairing aortic medial degeneration and ferroptosis in AD, potentially reducing the incidence of aortic dissection rupture.

Resistive index of central retinal artery, aortic arterial stiffness and OCTA correlated parameters in the early stage of fabry disease.

This study aimed to evaluate the impact of Fabry disease (FD) on retinal microvasculature using optical coherence tomography angiography (OCTA), arterial stiffness, and the resistive index (RI) of the central retinal artery (CRA) in early disease stages. Twenty-nine genetically confirmed FD patients and twenty-six healthy controls were enrolled. Vessel density (VD) values of the superficial, deep, and choriocapillaris plexuses (SCP, DCP, and CC) were measured via OCTA. CRA RI was studied using color Doppler and grayscale sonography, and aortic pulse wave velocity (PWV) was assessed with the Complior method. CRA RI was significantly lower in the control group compared to the Fabry group (p < 0.001). Central VD was found to be significantly higher in the control group compared to the Fabry group in all the retinal layers (SCP (p < 0.001), DCP (p < 0.005), CC (p < 0.001)). PWV was significantly higher in the Fabry group than in the control group (p = 0.03). Fabry disease patients demonstrate elevated arterial stiffness, increased CRA RI, and diminished retinal microvascular density compared to healthy controls, indicating early ocular damage. Continuous monitoring and targeted screening for organ impairment are crucial in FD management. Identifying biomarkers for assessing ocular vascular involvement and treatment response is imperative. Further research is needed.

Multi-stage cascade GAN for synthesis of contrast enhancement CT aorta images from non-contrast CT.

Recently in diagnosis of Aortic dissection (AD), the synthesis of contrast enhanced CT (CE-CT) images from non-contrast CT (NC-CT) images is an important topic. Existing methods have achieved some results but are unable to synthesize a continuous and clear intimal flap on NC-CT images. In this paper, we propose a multi-stage cascade generative adversarial network (MCGAN) to explicitly capture the features of the intimal flap for a better synthesis of aortic dissection images. For the intimal flap with variable shapes and more detailed features, we extract features in two ways: dense residual attention blocks (DRAB) are integrated to extract shallow features and UNet is employed to extract deep features; then deep features and shallow features are cascaded and fused. For incomplete flaps or lack of details, we use spatial attention and channel attention to extract key features and locations. At the same time, multi-scale fusion is used to ensure the continuity of the intimal flap. We perform the experiment on a set of 124 patients (62 with AD and 62 without AD). The evaluation results show that the synthesized images have the same characteristics as the real images and achieves better results than the popular methods.

Magnetic Resonance Imaging of Temporomandibular Joint and Aortic Root Score in Fibrillinopathies.

Background and Objectives: Fibrillinopathies have different phenotypic expression: Marfan-like skeleton features, MLSF; mitral valve prolapse syndrome, MVPS; MASS phenotype, M = mitral valve prolapse, MVP, A = aortic root dilation, S = skeletal features, and the second S = (cutaneous) striae; Marfan Syndrome, MS. The study had the following main objectives: the correlation between disc displacement, DD (a major sign for temporomandibular joint dysfunction, TMDs) on magnetic resonance imaging, MRI, and aortic Z score (a major sign for aortic root dilation) on echocardiography; the predictive value of DD towards aortic Z score. DD had 2 types of severity: DD with reduction (the mild type, DDwR), and DD without reduction (the severe type, DDwoR). Materials and Methods: The type of fibrillinopathy was precised by clinical exam (systemic score), ophthalmic exam (for ectopia lentis), and echocardiography (aortic Z score, MVP). Medical treatment consisted of betablockers, BB (for patients with tachycardia), or angiotensin II receptor blockers, ARB. Surgical treatment was addressed to aortic root aneurysm, and severe mitral regurgitation, MR. DD benefited from dental conservatory treatment or surgical restoration. Results: DD-Z score had a powerful correlation in MASS (Rho = 0.787, p < 0.01), and in MS patients (Rho = 0.819, p < 0.01). For the entire sample, both DDwR-Z score and DDwoR-Z score had a moderate correlation (Rho = 0.469, and respectively 0.669). Furthermore, DD was an important predictor for Z score. DDwoR had a double power of prediction for the Z score compared with DDwR (B coefficient = 1.661 for DDwR and 3.281 for DDwoR). Conclusions: TMDs had a powerful correlation with aortic root dilation in MASS and MS patients from the sample. Likewise, TMDs was a major predictor for aortic root dilation, in the entire sample. In clinical practice, we can utilize an extracardiac finding, TMDs, obtained by a non-invasive technique, MRI, for cardiac severity stratification of fibrillinopathies.

Automated Quantification of Simple and Complex Aortic Flow Using 2D Phase Contrast MRI.

(1) Background and Objectives: Flow assessment using cardiovascular magnetic resonance (CMR) provides important implications in determining physiologic parameters and clinically important markers. However, post-processing of CMR images remains labor- and time-intensive. This study aims to assess the validity and repeatability of fully automated segmentation of phase contrast velocity-encoded aortic root plane. (2) Materials and Methods: Aortic root images from 125 patients are segmented by artificial intelligence (AI), developed using convolutional neural networks and trained with a multicentre cohort of 160 subjects. Derived simple flow indices (forward and backward flow, systolic flow and velocity) and complex indices (aortic maximum area, systolic flow reversal ratio, flow displacement, and its angle change) were compared with those derived from manual contours. (3) Results: AI-derived simple flow indices yielded excellent repeatability compared to human segmentation (p < 0.001), with an insignificant level of bias. Complex flow indices feature good to excellent repeatability (p < 0.001), with insignificant levels of bias except flow displacement angle change and systolic retrograde flow yielding significant levels of bias (p < 0.001 and p < 0.05, respectively). (4) Conclusions: Automated flow quantification using aortic root images is comparable to human segmentation and has good to excellent repeatability. However, flow helicity and systolic retrograde flow are associated with a significant level of bias. Overall, all parameters show clinical repeatability.

Type a aortic dissection after aortic wrapping performed 26 years ago: a case report.

BACKGROUND: Aortic wrapping (AW) has been performed as a less invasive alternative to aortoplasty. However, AW can also cause long-term aortic complications. In this report, we present a rare case of a dissecting aortic aneurysm between the proximal side of the wrap and the sinotubular junction after AW. CASE PRESENTATION: A female patient had undergone urgent aortic valve replacement with a 19-mm mechanical valve to treat infective endocarditis and AW to treat an enlarged ascending aorta 26 years prior. At the age of 71 years, the patient was diagnosed with a dissecting aortic aneurysm between the proximal side of the wrap and the sinotubular junction. We performed graft replacement of the ascending aorta, including complete resection of the wrap. The patient was discharged on postoperative day 10, and there have been no cardiovascular events during her ongoing follow up. CONCLUSIONS: AW in younger patients can lead to late aortic complications. Careful consideration should be paid when performing AW in young patients, and patients who have previously undergone AW require strict life-long follow-up.

Low shear-induced fibrillar fibronectin: comparative analyses of morphologies and cellular effects on bovine aortic endothelial cell adhesion and proliferation.

Wall shear stress (WSS) is a critical factor in vascular biology, and both high and low WSS are implicated in atherosclerosis. Fibronectin (FN) is a key extracellular matrix protein that plays an important role in cell activities. Under high shear stress, plasma FN undergoes fibrillogenesis; however, its behavior under low shear stress remains unclear. This study aimed to investigate the formation ofin vitrocell-free fibrillar FN (FFN) under low shear rate conditions and its effect on bovine aortic endothelial cell behavior. FN (500µg ml-1) was perfused through slide chambers at three flow rates (0.16 ml h-1, 0.25 ml h-1, and 0.48 ml h-1), corresponding to low shear rates of 0.35 s-1, 0.55 s-1, and 1.05 s-1, respectively, for 4 h at room temperature. The formed FN matrices were observed using fluorescence microscopy and scanning electron microscopy. Under low shear rates, distinct FN matrix structures were observed. FFN0.48 formed immense fibrils with smooth surfaces, FFN0.25 formed a matrix with a rough surface, and FFN16 exhibited nodular structures. FFN0.25 supported cell activities to a greater extent than native FN and other FFN surfaces. Our study suggests that abnormally low shear conditions impact FN structure and function and enhance the understanding of FN fibrillogenesis in vascular biology, particularly in atherosclerosis.

Circulating Matrix Metalloproteinases for Prediction of Aortic Dilatation in Children with Bicuspid Aortic Valve: A Single-Center, Observational Study.

Circulating biomarkers have been proposed for early identification of aortic dilatation progression associated with bicuspid aortic valve (BAV), but matrix metalloproteinases (MMPs) are distinguished as signatures of increased extracellular matrix degradation, a landmark of aneurysm formation. The current study aims to identify the role of MMP-1, MMP-2, MMP-9, and the MMP inhibitor, TIMP-1, in identifying aortic dilation in children with BAV. We conducted a study on 73 children divided into two study groups, depending on the presence of aortic dilatation (group 1-43 BAV controls and group 2-30 children with BAV and aortic dilatation). Each patient underwent a cardiac ultrasound and, in each case, serum MMP-1, MMP-2, MMP-9, and TIMP-1 were quantified using xMAP technology. Comparison of the MMPs between the two study groups revealed significantly higher values only in the case of TIMP-1, among BAV controls. Moreover, the same TIMP-1 inversely correlated with aortic annulus absolute size and z score, as well as with ascending aorta z score. No particular correlation between the aortic phenotype and the presence of aortic dilatation was found. Future longitudinal research starting at pediatric ages could show the significance of MMPs screening in BAV individuals as predictors of aortic aneurysm formation.

Dapagliflozin mitigates cellular stress and inflammation through PI3K/AKT pathway modulation in cardiomyocytes, aortic endothelial cells, and stem cell-derived ß cells.

Dapagliflozin (DAPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is well-recognized for its therapeutic benefits in type 2 diabetes (T2D) and cardiovascular diseases. In this comprehensive in vitro study, we investigated DAPA's effects on cardiomyocytes, aortic endothelial cells (AECs), and stem cell-derived beta cells (SC-ß), focusing on its impact on hypertrophy, inflammation, and cellular stress. Our results demonstrate that DAPA effectively attenuates isoproterenol (ISO)-induced hypertrophy in cardiomyocytes, reducing cell size and improving cellular structure. Mechanistically, DAPA mitigates reactive oxygen species (ROS) production and inflammation by activating the AKT pathway, which influences downstream markers of fibrosis, hypertrophy, and inflammation. Additionally, DAPA's modulation of SGLT2, the Na+/H + exchanger 1 (NHE1), and glucose transporter (GLUT 1) type 1 highlights its critical role in maintaining cellular ion balance and glucose metabolism, providing insights into its cardioprotective mechanisms. In aortic endothelial cells (AECs), DAPA exhibited notable anti-inflammatory properties by restoring AKT and phosphoinositide 3-kinase (PI3K) expression, enhancing mitogen-activated protein kinase (MAPK) activation, and downregulating inflammatory cytokines at both the gene and protein levels. Furthermore, DAPA alleviated tumor necrosis factor (TNFα)-induced inflammation and stress responses while enhancing endothelial nitric oxide synthase (eNOS) expression, suggesting its potential to preserve vascular function and improve endothelial health. Investigating SC-ß cells, we found that DAPA enhances insulin functionality without altering cell identity, indicating potential benefits for diabetes management. DAPA also upregulated MAFA, PI3K, and NRF2 expression, positively influencing ß-cell function and stress response. Additionally, it attenuated NLRP3 activation in inflammation and reduced NHE1 and glucose-regulated protein GRP78 expression, offering novel insights into its anti-inflammatory and stress-modulating effects. Overall, our findings elucidate the multifaceted therapeutic potential of DAPA across various cellular models, emphasizing its role in mitigating hypertrophy, inflammation, and cellular stress through the activation of the AKT pathway and other signaling cascades. These mechanisms may not only contribute to enhanced cardiac and endothelial function but also underscore DAPA's potential to address metabolic dysregulation in T2D.

1. DAPA effectively attenuates ISO-induced cardiomyocyte hypertrophy by reducing cell size and improving cellular structure. 2. DAPA exhibits anti-inflammatory properties in AECs by restoring AKT and PI3K expression, upregulating MAPK activation, and downregulating inflammatory gene expression. 3. DAPA enhances insulin functionality in SC-ß cells without altering cell identity, suggesting potential benefits in diabetes management. 4. DAPA's modulation of SGLT2, NHE1, and GLUT1 expression in cardiomyocytes underscores its role in cellular ion balance and glucose metabolism, contributing to its cardioprotective mechanisms. 5. DAPA alleviates TNFα-induced inflammation and stress responses in AECs, while enhancing eNOS expression, indicating its potential to preserve vascular function. 6. DAPA attenuates NLRP3 activation and reduces NHE1 and GRP78 expression in SC-ß cells, offering novel insights into its anti-inflammatory and stress-modulating effects.

Normative computed tomography angiography values of the aortic root, aorta, and aortic arch in children.

Normative values for intracardiac and extracardiac vascular structures help in understanding normal growth and changes over time in children; this normative data is not currently available for ECG-gated computed tomography angiography (CTA). We sought to establish ECG-gated CTA-derived normative values for the aortic root, aorta, and aortic arch in children. Aortic root, ascending aorta, aortic arch, and descending aorta were measured in systole and diastole in 100 subjects who had ECG-gated CTA at our center between January 2015 and December 2020 and met our inclusion criteria. The allometric exponent (AE) for each parameter was derived, and the parameter/body surface areaAE (BSAAE) was established using the previously described methods. Using this data, normalized mean, cross-sectional area, and standard deviation were calculated. Z-score curves were plotted in relation to the BSA for all measurements. CONCLUSION: Our study reports systolic and diastolic ECG-gated CTA Z-scores along with normative curves in relation to BSA for the aortic root, aorta, and aortic arch in children. WHAT IS KNOWN: • Normative data for intracardiac and extracardiac vascular structures in the pediatric population are available for echocardiography, cardiac MRI and non-ECG gated CTA. • Z-scores with standard deviations are commonly used in children, but SDs are not constant across body sizes due to heteroscedasticity. WHAT IS NEW: • Allometric exponent was derived for each parameter and the parameter/body surface area (BSA) was established. • This is the first ECG-gated CTA study to provide normative en face systolic, diastolic diameters and cross-sectional areas along with Z-scores and normative curves for the aortic root, aorta and aortic arch in children.

The combination of Florida sleeve and Ozaki procedures for aortic root repair.

It is generally accepted that the definitive treatment for irreparable aortic root disease is aortic root replacement with a valved conduit - the Bentall procedure. However, we try to follow a reparative strategy for all aortic root pathology whenever possible. Our "root-sparing" philosophy is achieved by restoration of physiological aortic root dimensions by the Florida sleeve technique and aortic cusp substitution by neocuspidization. The combination of both strategies allows for full reconstruction of the root, instead of its replacement. Our modification is called FLOZ, from "FLorida + OZaki".

The prognostic impact of maximal aortic diameter on acute type B aortic dissection progression in a Chinese population.

Currently, evidence concerning the link between maximal aortic diameter and in-hospital mortality in cases of acute type B aortic dissection (ATBAD) is insufficient. Thus, this study aimed to explore the relationship between the maximal aortic diameter at the time of admission and the early prognosis of patients diagnosed with ATBAD. A total of 678 patients with ATBAD were included between January 2016 and December 2018, during which their clinical data was gathered. The independent variable analyzed was the maximal diameter of the aorta, while the dependent variable was mortality during hospitalization. Factors considered in this analysis included the patients' age, gender, body mass index (BMI), medical history of hypertension, stroke, diabetes, atherosclerosis, smoking habits, chronic kidney insufficiency, time until presentation, systolic and diastolic blood pressures, ejection fraction, presence of aortic regurgitation, symptoms, involvement of abdominal vessels, laboratory findings, and treatment approaches. Of these patients collected, the mean age was 56.03 ± 12.22 years, and approximately 82.45% of them were male. After analysis, it was found that the maximal aortic diameter of patients with ATBAD was positively correlated with in-hospital mortality (OR = 1.06, 95% CI 1.03 to 1.10). Surprisingly, a J curve relationship was detected between maximal aortic diameter (point 31 mm) and in-hospital death for patients with ATBAD. The effect sizes and confidence intervals of the right (maximal aortic diameter > 31 mm) and left (maximal aortic diameter ≤ 31 mm) aspects of the inflection point were 1.06 (1.02-1.11) and 1.03 (0.83-1.28), respectively. In addition, the stratified analysis showed a stable relationship between maximal aortic diameter and in-hospital mortality, while there was no significant difference in the interaction between different subgroups. In patients with ATBAD, a J-curve relationship was identified between the maximal aortic diameter and in-hospital mortality. Specifically, when the maximal aortic diameter exceeds 31 mm, a positive correlation with in-hospital death was observed.

Effects of pedicle subtraction osteotomy on aortic morphology and hemodynamics in ankylosing spondylitis with kyphosis: a finite element analysis study.

Osteotomy can correct kyphosis, restore the spinal sequence, and restore the healthy appearance of a patient. However, the aorta is stretched during pedicle subtraction osteotomy (PSO), and some surgeons are concerned about aortic injury. We used finite element analysis to construct an aortic model to simulate hemodynamic changes during osteotomy. 16 patients with ankylosing spondylitis kyphosis who had undergone a two-level osteotomy at the L1 and L3 levels was included in this study. Aortic computed tomography angiography (CTA) was performed, and a 3D image model was constructed. The length, transverse diameter, and curvature of the aorta were used to evaluate morphological changes. Finite element analysis was used to analyze the changes in aortic fluid dynamics. Blood pressure, wall shear stress, and blood flow velocity were compared pre- and postoperatively. The overall length of the aorta before surgery was 424.3 ± 42.9 mm, and the overall length of the aorta after surgery was 436.2 ± 54.8 mm. The aortic curvature decreased from 0.27 ± 0.13 to 0.17 ± 0.09. The mean transverse diameter of the aorta did not change (19.3 ± 6.6 vs. 19.2 ± 7.4 mm, P > 0.05). The blood flow velocity (2.8 ± 1.1 vs. 1.5 ± 0.8 m/s, P < 0.05), blood pressure (6.6 ± 1.7 vs. 4.3 ± 1.2 Kpa, P < 0.05), and wall shear stress (47.6 ± 17.3 vs. 22.3 ± 8.6, P < 0.05) at the T10-L4 level decreased postoperatively. Changes in LL were significantly correlated with changes in ld, dc, blood flow velocity, blood pressure and wall shear stress (ld : r = 0.713, P < 0.001; dc: r = 0.626,P = 0.010; blood flow velocity: r= - 0.541, P = 0.041; blood pressure: r = - 0.601, P = 0.016; wall shear stress: r= - 0.594, P = 0.027). The aorta was stretched, and its curvature decreased. The mean transverse diameter of the aorta did not change. Blood flow velocity, blood pressure, and wall shear stress decreased after surgery. Our study provides hemodynamic support for the possible cardiovascular benefits of osteotomes.