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The Journal of Biological Chemistry Jun 2024Obesity is a major risk factor for liver and cardiovascular diseases. However, obesity-driven mechanisms that contribute to the pathogenesis of multiple organ diseases...
Obesity is a major risk factor for liver and cardiovascular diseases. However, obesity-driven mechanisms that contribute to the pathogenesis of multiple organ diseases are still obscure and treatment is inadequate. We hypothesized that increased glucose-6-phosphate dehydrogenase (G6PD), the key rate-limiting enzyme in the pentose shunt, is critical in evoking metabolic reprogramming in multiple organs and is a significant contributor to the pathogenesis of liver and cardiovascular diseases. G6PD is induced by carbohydrate-rich diet and insulin. Long-term (8 months) high-fat diet (HFD) feeding increased body weight and elicited metabolic reprogramming in visceral fat, liver, and aorta, of the wild-type rats. In addition, HFD increased inflammatory chemokines in visceral fat. Interestingly, CRISPR-edited loss-of-function Mediterranean G6PD variant (G6PD) rats, which mimic human polymorphism, moderated HFD-induced weight gain and metabolic reprogramming in visceral fat, liver, and aorta. The G6PD variant prevented HFD-induced CCL7 and adipocyte hypertrophy. Furthermore, the G6PD variant increased Magel2 - a gene encoding circadian clock-related protein that suppresses obesity associated with Prader-Willi syndrome - and reduced HFD-induced non-alcoholic fatty liver. Additionally, the G6PD variant reduced aging-induced aortic stiffening. Our findings suggest G6PD is a regulator of HFD-induced obesity, adipocyte hypertrophy, and fatty liver.
PubMed: 38876306
DOI: 10.1016/j.jbc.2024.107460 -
Medicine Jun 2024Waist-to-height ratio (WtHR) is a validated biomarker of central obesity that appears to be preferable to other body composition measurements in the evaluation of... (Observational Study)
Observational Study
Waist-to-height ratio (WtHR) is a validated biomarker of central obesity that appears to be preferable to other body composition measurements in the evaluation of cardiovascular disease. The goal of this research was to explore the connection between WtHR and abdominal aortic calcification (AAC) among adults. On the basis of data from the 2013 to 2014 National Health and Nutrition Examination Survey, multivariate logistic regression, sensitivity analysis, as well as smoothed curve fitting were used to evaluate the connection between WtHR and AAC. Subgroup analyses along with interaction tests were done to see if this link was consistent across populations. Among 3079 participants aged >40 years, there was a negative association between WtHR and ACC. Each 1-unit emergence of WtHR was related to a 2% reduction in the probability of severe AAC in the entirely adjusted model (odds ratio = 0.02, 95% confidence interval: [0.00-0.12]). Participants in the highest WtHR quartile were 39% less likely to acquire severe AAC compared with those in the lowest quartile. (odds ratio = 0.61, 95% confidence interval: [0.37-1.00]). This negative association was more pronounced in the diabetes subgroup. We discovered a reversed U-shaped association between WtHR as well as AAC score utilizing a 2-stage linear regression model, with an intersection point of 0.56. WtHR was negatively associated with AAC among US adults.
Topics: Humans; Cross-Sectional Studies; Male; Aorta, Abdominal; Middle Aged; Female; Vascular Calcification; Waist-Height Ratio; Nutrition Surveys; Adult; Aortic Diseases; Aged; Risk Factors; Obesity, Abdominal
PubMed: 38875360
DOI: 10.1097/MD.0000000000038608 -
Frontiers in Cardiovascular Medicine 2024The left subclavian artery (LSA) can be intentionally covered by a stent graft to acquire adequate landing zones for a proximal entry tear near the LSA during thoracic...
BACKGROUND
The left subclavian artery (LSA) can be intentionally covered by a stent graft to acquire adequate landing zones for a proximal entry tear near the LSA during thoracic endovascular aortic repair (TEVAR). The Castor single-branched stent graft is designed to treat type B aortic dissection (TBAD) to retain the LSA during TEVAR. This study investigates clinical outcomes, aortic remodeling, and abdominal aortic perfusion patterns after TEVAR with the novel Castor device.
METHODS
From November 2020 to June 2023, 29 patients with TBAD involving the LSA were treated with the Castor single-branched stent graft. In-hospital clinical outcome and aortic computed tomography angiography (CTA) data were analyzed. CTA was performed preoperatively and at follow-up to observe stent morphology; branch patency; endoleak; change in true lumen (TL), false lumen (FL), and transaortic diameters; and abdominal aortic branch perfusion pattern.
RESULTS
The technical success rate was 96.6%. One failure was that the branch section did not completely enter the LSA and the main body migrated distally. No in-hospital mortality, paraplegia, or stroke occurred. During follow-up, one type Ib endoleak, four distal new entry tears, and one recurrent type A dissection arose from a new entry tear at the ascending aorta, no stent migration was observed, and the branch patency rate was 100%. At the thoracic aorta, TL diameters significantly increased, FL diameters markedly decreased, and FL was partially or completely thrombosed in most patients at follow-up. At the abdominal aorta, we observed 33.3% of TL growth and 66.7% of TL stabilization or shrinkage. The initial TL ratio at iliac bifurcation negatively predicted abdominal TL growth after TEVAR with a cutoff of 21.0%. Of the 102 abdominal aortic branches, 94.1% of the branches showed no change in perfusion pattern, 3.9% of the branches had an increased TL perfusion, and 2.0% of the branches had an increased FL contribution.
CONCLUSION
The Castor unibody single-branched stent graft offers an efficient endovascular treatment for TBAD involving the LSA. TEVAR with the Castor device effectively induced thoracic FL thrombosis and thoracic TL enlargement and resulted in abdominal TL growth when the initial TL ratio at iliac bifurcation is less than 21.0%. Abdominal aortic branch perfusion patterns remain relatively stable after TEVAR with the Castor stent graft.
PubMed: 38873267
DOI: 10.3389/fcvm.2024.1370908 -
Cureus May 2024Foreign body granulomas following endovascular treatment are rare complications and are mostly reported in the brain or cutaneous vascular tissues. To the best of our...
Foreign body granulomas following endovascular treatment are rare complications and are mostly reported in the brain or cutaneous vascular tissues. To the best of our knowledge, no study to date has reported on foreign body granulomas in the abdomen after injection of N-butyl-2-cyanoacrylate (NBCA)-lipiodol mixture into the abdominal arteries. This study reports a case of foreign body granuloma that appeared 12 months after the embolization of a right internal iliac artery aneurysm using an NBCA-lipiodol mixture, which posed challenges in differentiation from malignant tumors. We present a 77-year-old man who underwent embolization of a right internal iliac artery aneurysm and open surgical repair of an abdominal aortic aneurysm. A contrast-enhanced CT performed 12 months postoperatively revealed a right-sided retroperitoneal mass surrounding the iliopsoas muscle. The mass contained multiple, small, hyperdense areas, suggesting the migration of the NBCA-lipiodol mixture casts from the embolized right internal iliac artery aneurysm. The differential diagnosis included foreign body granuloma, lymphoma, and sarcoma. A biopsy of the lesion revealed a granuloma with various stages of inflammation, no hemosiderin deposition, multinucleated giant cells, and foam cells containing fat, and was diagnosed with a foreign body granuloma. Special staining for microorganisms revealed no findings suggestive of infection. Because the patient was asymptomatic, no treatment was administered. Contrast-enhanced CT at 24 months postoperatively showed shrinkage of the mass, with no change in size noted at 48 months postoperatively. This report highlights a foreign body granuloma that mimicked malignant tumors. Extravascular migration of the NBCA-lipiodol mixture casts likely contributed to granuloma formation. Radiologists should consider foreign body granulomas after embolization using NBCA into the abdominal arteries.
PubMed: 38868262
DOI: 10.7759/cureus.60187 -
Cardiovascular Diabetology Jun 2024There is currently limited understanding of the relationship between copeptin, the midregional portion of proadrenomedullin (MRproADM) and the midregional fragment of...
OBJECTIVES
There is currently limited understanding of the relationship between copeptin, the midregional portion of proadrenomedullin (MRproADM) and the midregional fragment of the N-terminal of proatrial natriuretic peptide (MRproANP), and arterial disorders. Toe brachial index (TBI) and aortic pulse wave velocity (aPWV) are established parameters for detecting arterial disorders. This study evaluated whether copeptin, MRproADM, and MRproANP were associated with TBI and aPWV in patients with type 2 diabetes with no history of cardiovascular disease (CVD).
METHODS
In the CARDIPP study, a cross-sectional analysis of 519 patients with type 2 diabetes aged 55-65 years with no history of CVD at baseline, had complete data on copeptin, MRproADM, MRproANP, TBI, and aPWV was performed. Linear regression analysis was used to investigate the associations between conventional CVD risk factors, copeptin, MRproADM, MRproANP, TBI, and aPWV.
RESULTS
Copeptin was associated with TBI (β-0.0020, CI-0.0035- (-0.0005), p = 0.010) and aPWV (β 0.023, CI 0.002-0.044, p = 0.035). These associations were independent of age, sex, diabetes duration, mean 24-hour ambulatory systolic blood pressure, glycated hemoglobin A1c, total cholesterol, estimated glomerular filtration rate, body mass index, and active smoking.
CONCLUSIONS
Plasma copeptin may be a helpful surrogate for identifying individuals at higher risk for arterial disorders.
TRIAL REGISTRATION
ClinicalTrials.gov identifier NCT010497377.
Topics: Humans; Glycopeptides; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Male; Middle Aged; Female; Biomarkers; Aged; Adrenomedullin; Atrial Natriuretic Factor; Vascular Stiffness; Peptide Fragments; Pulse Wave Analysis; Diabetic Angiopathies; Protein Precursors; Risk Assessment; Predictive Value of Tests
PubMed: 38867292
DOI: 10.1186/s12933-024-02291-2 -
Xenotransplantation 2024Orthotopic cardiac xenotransplantation has seen notable improvement, leading to the first compassionate use in 2022. However, it remains challenging to define the...
Hemodynamics in pig-to-baboon heterotopic thoracic cardiac xenotransplantation: Recovery from perioperative cardiac xenograft dysfunction and impairment by cardiac overgrowth.
INTRODUCTION
Orthotopic cardiac xenotransplantation has seen notable improvement, leading to the first compassionate use in 2022. However, it remains challenging to define the clinical application of cardiac xenotransplantation, including the back-up strategy in case of xenograft failure. In this regard, the heterotopic thoracic technique could be an alternative to the orthotopic procedure. We present hemodynamic data of heterotopic thoracic pig-to-baboon transplantation experiments, focusing on perioperative xenograft dysfunction and xenograft overgrowth.
METHODS
We used 17 genetically modified piglets as donors for heterotopic thoracic xenogeneic cardiac transplantation into captive-bred baboons. In all animals, pressure probes were implanted in the graft's left ventricle and the recipient's ascending aorta and hemodynamic data (graft pressure, aortic pressure and recipient's heart rate) were recorded continuously.
RESULTS
Aortic pressures and heart rates of the recipients' hearts were postoperatively stable in all experiments. After reperfusion, three grafts presented with low left ventricular pressure indicating perioperative cardiac dysfunction (PCXD). These animals recovered from PCXD within 48 h under support of the recipient's heart and there was no difference in survival compared to the other 14 ones. After 48 h, graft pressure increased up to 200 mmHg in all 17 animals with two different time-patterns. This led to a progressive gradient between graft and aortic pressure. With increasing gradient, the grafts stopped contributing to cardiac output. Grafts showed a marked weight increase from implantation to explantation.
CONCLUSION
The heterotopic thoracic cardiac xenotransplantation technique is a possible method to overcome PCXD in early clinical trials and an experimental tool to get a better understanding of PCXD. The peculiar hemodynamic situation of increasing graft pressure but missing graft's output indicates outflow tract obstruction due to cardiac overgrowth. The heterotopic thoracic technique should be successful when using current strategies of immunosuppression, organ preservation and donor pigs with smaller body and organ size.
Topics: Animals; Transplantation, Heterologous; Heart Transplantation; Swine; Hemodynamics; Heterografts; Papio; Graft Survival; Transplantation, Heterotopic; Animals, Genetically Modified; Graft Rejection; Humans
PubMed: 38864375
DOI: 10.1111/xen.12841 -
European Heart Journal Open May 2024The ageing process notably induces structural changes in the arterial system, primarily manifesting as increased aortic stiffness, a precursor to cardiovascular events....
AIMS
The ageing process notably induces structural changes in the arterial system, primarily manifesting as increased aortic stiffness, a precursor to cardiovascular events. While wave separation analysis is a robust tool for decomposing the components of blood pressure waveform, its relationship with cardiovascular events, such as aortic stiffening, is incompletely understood. Furthermore, its applicability has been limited due to the need for concurrent measurements of pressure and flow. Our aim in this study addresses this gap by introducing a spectral regression learning method for pressure-only wave separation analysis.
METHODS AND RESULTS
Leveraging data from the Framingham Heart Study (2640 individuals, 55% women), we evaluate the accuracy of pressure-only estimates, their interchangeability with a reference method based on ultrasound-derived flow waves, and their association with carotid-femoral pulse wave velocity (PWV). Method-derived estimates are strongly correlated with the reference ones for forward wave amplitude ( ), backward wave amplitude ( ), and reflection index ( ) and moderately correlated with a time delay between forward and backward waves ( ). The proposed pressure-only method shows interchangeability with the reference method through covariate analysis. Adjusting for age, sex, body size, mean blood pressure, and heart rate, the results suggest that both pressure-only and pressure-flow evaluations of wave separation parameters yield similar model performances for predicting carotid-femoral PWV, with forward wave amplitude being the only significant factor ( < 0.001; 95% confidence interval, 0.056-0.097).
CONCLUSION
We propose an interchangeable pressure-only wave separation analysis method and demonstrate its clinical applicability in capturing aortic stiffening. The proposed method provides a valuable non-invasive tool for assessing cardiovascular health.
PubMed: 38863521
DOI: 10.1093/ehjopen/oeae040 -
Critical Care (London, England) Jun 2024Women are at higher risk of mortality from many acute cardiovascular conditions, but studies have demonstrated differing findings regarding the mortality of cardiogenic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Women are at higher risk of mortality from many acute cardiovascular conditions, but studies have demonstrated differing findings regarding the mortality of cardiogenic shock in women and men. To examine differences in 30-day mortality and mechanical circulatory support use by sex in patients with cardiogenic shock.
MAIN BODY
Cochrane Central, PubMed, MEDLINE and EMBASE were searched in April 2024. Studies were included if they were randomised controlled trials or observational studies, included adult patients with cardiogenic shock, and reported at least one of the following outcomes by sex: raw mortality, adjusted mortality (odds ratio) or use of mechanical circulatory support. Out of 4448 studies identified, 81 met inclusion criteria, pooling a total of 656,754 women and 1,018,036 men. In the unadjusted analysis for female sex and combined in-hospital and 30-day mortality, women had higher odds of mortality (Odds Ratio (OR) 1.35, 95% confidence interval (CI) 1.26-1.44, p < 0.001). Pooled unadjusted mortality was 35.9% in men and 40.8% in women (p < 0.001). When only studies reporting adjusted ORs were included, combined in-hospital/30-day mortality remained higher in women (OR 1.10, 95% CI 1.06-1.15, p < 0.001). These effects remained consistent across subgroups of acute myocardial infarction- and heart failure- related cardiogenic shock. Overall, women were less likely to receive mechanical support than men (OR = 0.67, 95% CI 0.57-0.79, p < 0.001); specifically, they were less likely to be treated with intra-aortic balloon pump (OR = 0.79, 95% CI 0.71-0.89, p < 0.001) or extracorporeal membrane oxygenation (OR = 0.84, 95% 0.71-0.99, p = 0.045). No significant difference was seen with use of percutaneous ventricular assist devices (OR = 0.82, 95% CI 0.51-1.33, p = 0.42).
CONCLUSION
Even when adjusted for confounders, mortality for cardiogenic shock in women is approximately 10% higher than men. This effect is seen in both acute myocardial infarction and heart failure cardiogenic shock. Women with cardiogenic shock are less likely to be treated with mechanical circulatory support than men. Clinicians should make immediate efforts to ensure the prompt diagnosis and aggressive treatment of cardiogenic shock in women.
Topics: Humans; Shock, Cardiogenic; Female; Male; Sex Factors; Treatment Outcome
PubMed: 38845019
DOI: 10.1186/s13054-024-04973-5 -
Scientific Data Jun 2024Aortic dissections (ADs) are serious conditions of the main artery of the human body, where a tear in the inner layer of the aortic wall leads to the formation of a new...
Aortic dissections (ADs) are serious conditions of the main artery of the human body, where a tear in the inner layer of the aortic wall leads to the formation of a new blood flow channel, named false lumen. ADs affecting the aorta distally to the left subclavian artery are classified as a Stanford type B aortic dissection (type B AD). This is linked to substantial morbidity and mortality, however, the course of the disease for the individual case is often unpredictable. Computed tomography angiography (CTA) is the gold standard for the diagnosis of type B AD. To advance the tools available for the analysis of CTA scans, we provide a CTA collection of 40 type B AD cases from clinical routine with corresponding expert segmentations of the true and false lumina. Segmented CTA scans might aid clinicians in decision making, especially if it is possible to fully automate the process. Therefore, the data collection is meant to be used to develop, train and test algorithms.
Topics: Humans; Aortic Dissection; Computed Tomography Angiography; Algorithms; Artificial Intelligence
PubMed: 38844767
DOI: 10.1038/s41597-024-03284-2