111 research outputs found
E-cigarette exposure augments murine abdominal aortic aneurysm development: role of Chil1
No full textAbstract
Aims
Abdominal aortic aneurysm (AAA) is a common cardiovascular disease with a strong correlation to smoking, although underlying mechanisms have been minimally explored. Electronic cigarettes (e-cigs) have gained recent broad popularity and can deliver nicotine at comparable levels to tobacco cigarettes, but effects on AAA development are unknown.
Methods and Results
We evaluated the impact of daily e-cig vaping with nicotine on AAA using two complementary murine models and found that exposure enhanced aneurysm development in both models and genders. E-cigs induced changes in key mediators of AAA development including cytokine chitinase-3-like protein 1 (CHI3L1/Chil1) and its targeting microRNA-24 (miR-24). We show that nicotine triggers inflammatory signaling and reactive oxygen species while modulating miR-24 and CHI3L1/Chil1 in vitro, and that Chil1 is crucial to e-cig-augmented aneurysm formation using a knockout model.
Conclusions
In conclusion our work shows increased aneurysm formation along with augmented vascular inflammation in response to e-cig exposure with nicotine. Further we identify Chil1 as a key mediator in this context. Our data raise concerns regarding the potentially harmful long-term effects of e-cig nicotine vaping.
Translational Perspective
Smoking is one of the most hazardous modifiable risk factors, with clear links to abdominal aortic aneurysm. E-cig vaping has displayed explosive growth in popularity. Intended for smoking cessation, it has been taken up by millions with no such clinical need, delivering nicotine addiction to new generations. The presumption that vaping is safer than tobacco overlooks the potential cardiovascular risks of nicotine. This study shows for the first time that inhaled e-cig nicotine vapor augments experimental AAA and aortic inflammation, suggests a mechanistic role for the cytokine Chil1/CHI3L1 and its regulator microRNA-24, and raises red flags regarding longitudinal e-cig safety
Ethanol Enhances Endothelial Rigidity by Targeting VE-Cadherin—Implications for Acute Aortic Dissection
No full text(1) Background: Acute aortic dissection (AAD) is caused by an endothelial entry tear followed by intimomedial delamination of the outer layers of the vessel wall. The established risk factors include hypertension and smoking. Another rising candidate risk factor is excessive alcohol consumption. This experimental study explores the effects of nicotine (Nic), angiotensin II (Ang II), and ethanol (EtOH) on human aortic endothelial cells (hAoEC). (2) Methods: HAoECs were exposed to Nic, Ang II, and EtOH at different dose levels. Cell migration was studied using the scratch assay and live-cell imaging. The metabolic viability and permeability capacity was investigated using the water-soluble tetrazolium (WST)-1 assay and an in vitro vascular permeability assay. Cell adherence was studied by utilizing the hanging drop assay. The transcriptional and protein level changes were analyzed by RT-qPCR, Western blotting and immunohistochemistry for major junctional complexing proteins. (3) Results: We observed reduced metabolic viability following Ang II and EtOH exposure vs. control. Further, cell adherence was enhanced by EtOH exposure prior to trituration and by all risk factors after trituration, which correlated with the increased gene and protein expression of VE-cadherin upon EtOH exposure. The cell migration capacity was reduced upon EtOH exposure vs. controls. (4) Conclusion: Marked functional changes were observed upon exposure to established and potential risk factors for AAD development in hAoECs. Our findings advocate for an enhanced mechanical rigidity in hAoECs in response to the three substances studied, which in turn might increase endothelial rigidity, suggesting a novel mechanism for developing an endothelial entry tear due to reduced deformability in response to increased shear and pulsatile stress
Application of high-dimensional mass cytometry to investigate the influence of bariatric surgery on the peripheral blood immune system of female morbid obese patients
No full textMorbid obesity, defined by a body mass index of equal or greater than 40 kg/m2, is associated with a reduced quality of life, severe comorbidities like diabetes, hypertension or cancer and a prevalent chronic low-grade inflammation as a result of an adipose tissue dysfunction and a disturbed microbiota-gut-brain axis. Due to its increasing numbers, methods for the treatment of obesity resulting in effective weight loss and remission of comorbidities are highly demanded. Bariatric surgery, including laparoscopic gastric sleeve and Roux-en-Y gastric bypass, is considered as the gold standard for the treatment of obesity leading to long-term weight loss, adaptions in the microbiota-gut-brain axis, a release of the chronic inflammation and an effective remission of comorbidities. However, as these procedures are irreversible and massively change the anatomical structure of the gastrointestinal tract, long-term consequences like malnutrition, anemia, and impairment of the skeletal bone system might occur. Although adipocytokines, gastrointestinal hormones, lipids and bacterial metabolites show high immunomodulatory potential, studies investigating the effects of bariatric surgery on the peripheral blood immune system are rare. In this study, morbid obese, female patients undergoing bariatric surgery at Ulm University Hospital were included. Additionally, healthy, lean, female probands with a body mass index of less or equal than 25 kg/m2 were recruited to serve as a control cohort. Mass cytometry was applied to detect phenotypical alterations in peripheral blood immune cells of morbid obese patients at high resolution level. Apart from that, the capability of bariatric surgery to reverse obesity associated alterations detected in peripheral blood immune cells was evaluated. Morbid obese patients showed typical signs of low-grade chronic inflammation, insulin resistance, disturbed lipid metabolism and altered levels of adipocytokines and gastrointestinal hormones characterized by high levels of C reactive protein, fibrinogen, insulin, triglycerides, total cholesterol, low-density lipoprotein, uric acid, leptin and resistin coming along with low levels of high-density lipoprotein, adiponectin, and ghrelin. Moreover, mass cytometry revealed shifts in innate and adaptive peripheral blood immune cells of morbid obese patients compared to the healthy controls. In morbid obese patients, innate immune cells like monocytes and granulocytic neutrophils showed elevated abundances and increased expression of activation and migration markers potentially promoting the migration to adipose tissue and supporting the onset of adipose tissue inflammation. Apart from that, monocytic myeloid derived suppressor cells, known to suppress T cell function, were increased in morbid obese patients. Moreover, monocytic subsets showed highly diminished expression of HLA-DR which is associated with a restricted immune response and a state of immunosuppression. Regarding adaptive immune cells, CD4+ T cells were shown to be highly influenced in the state of morbid obesity. Decreased levels of naïve T cells and increased levels of memory T cells, characterized by upregulation of IL-7 receptor subunit alpha could be observed. The disturbance of the CD4+ T cell compartment might be associated with a dysfunctional, prematurely aged thymus described in the state of morbid obesity. Interestingly, bariatric surgery was shown to effectively reverse most of the observed obesity-associated alterations within the first year post-surgery. Both procedures resulted in significant weight loss with high individual variation. Furthermore, bariatric surgery resulted in decreased levels of C-reactive protein, fibrinogen, leukocytes, insulin, glycated hemoglobin, triglycerides, uric acid and increased levels of HDL indicating the release of the low-grade chronic inflammation and metabolic improvements. Leptin and adiponectin levels also normalized after surgery. However, ghrelin levels further decreased after surgery and did not recover within the first year post-surgery. Bariatric surgery also normalized the levels of granulocytes and monocytes within the first year post-surgery but resulted in further decline of NK cells and CD4+ naïve T cells. HLA-DR expression of monocytes did also not recover within the first year post-surgery. Nevertheless, the levels of NK cells and CD4+ naïve T cells as well as monocytic HLA-DR expression normalized 15 – 19 months p.s., whereas the expression of IL-7 receptor subunit alpha was still increased on CD4+ memory T cells.
This study reveals a striking impact of morbid obesity on peripheral blood immune cells, which can be described by activated innate immune cells and a disturbed CD4+ T cell compartment which is comparable to age-related changes. Moreover, the study shows the power of bariatric surgery to effectively reverse obesity associated alterations including low-grade chronic inflammation, insulin resistance, disturbed adipocytokine levels and immune cell compartments but also puts emphasis on adaptions like unphysiologically decreased ghrelin levels that occur most likely due to the anatomical changes after surgery
NEXUS Arch: A Multicenter Study Evaluating the Initial Experience with a Novel Aortic Arch Stent Graft System
No full textTo assess the initial clinical experience with a novel endograft system (NEXUS Aortic Arch Stent Graft System) designed to treat aortic arch pathologies and address the morphology and hemodynamic challenges of the aortic arch
Effect of statin therapy on serum activity of proteinases and cytokines in patients with abdominal aortic aneurysm
No full textBernd Muehling1, Alexander Oberhuber1, Hubert Schelzig1, Gisela Bischoff1, Nikolaus Marx2, Ludger Sunder-Plassmann1, Karl H Orend11Department of Thoracic and Vascular surgery; 2Department of Internal Medicine, University of Ulm, Ulm, GermanyBackground and aims: Metalloproteinases (MMPs) are considered to be key enzymes in the pathogenesis of abdominal aortic aneurysms (AAA), with elevated levels in diseased aorta and in patient sera. Statins seem to exert an inhibitory effect on MMP activity in the aortic wall. No data exist on the effect of statins on serum activity of MMPs and inflammatory cytokines (interleukins, IL).Methods: The serum activities of MMP2 and MMP9, osteoprotegerin (OPG), and IL6 and IL10 in 63 patients undergoing elective infrarenal aneurysm repair were measured on the day before surgery. Levels were correlated to statin therapy and aneurysm diameter.Results: There was no significant difference between the two groups in the activity of circulating levels of MMP2/9, OPG, and IL6/10 in patients with infrarenal aortic aneurysm. IL6 levels in patients with AAA larger than 6 cm were significantly elevated; differences in serum activities of MMP2/9, OPG, and IL10 were not related to AAA diameter.Conclusion: Serum activities of MMP2/9, OPG, and IL6/10 are not correlated to statin therapy; IL6 levels are higher in patients with large aneurysms. Hence the effect of statin therapy in the treatment of aneurismal disease remains to be elucidated.Keywords: biomarkers, aneurismal disease, statin therap
Kidney Ischemia and Reperfusion Injury – Field of Glory or Warterloo for Erythropoietin?
No full textNEXUS Arch: A Multicenter Study Evaluating the Initial Experience With a Novel Aortic Arch Stent Graft System
No full textObjective:To assess the initial clinical experience with a novel endograft system (NEXUS Aortic Arch Stent Graft System) designed to treat aortic arch pathologies and address the morphology and hemodynamic challenges of the aortic arch. Summary Background Data:The aortic arch remains the most challenging part of the aorta for both open and endovascular repair. Transcatheter aortic arch repair has the potential to significantly reduce surgical risks. Methods:Patients underwent transcatheter aortic arch repair with a single branch, 2 stent graft system, implanted over a through-and-through guidewire from the brachiocephalic trunk, to the descending aorta with an ascending aorta stent graft. The ascending aorta stent graft is deployed into a designated docking sleeve to connect the 2 stent grafts and isolate the aortic arch pathology. Proximal landing zone in all cases was in Zone 0. Anatomical inclusion criteria included adequate landing zone in the ascending aorta, brachiocephalic trunk, and descending thoracic aorta. Preparatory debranching procedure was performed in all patients with carotid-carotid crossover bypass and left carotid to left subclavian bypass, or parallel graft from descending aorta to left subclavian artery. Safety and performance were evaluated through 1 year. Survival analysis used the Kaplan-Meier method. Results:Twenty-eight patients, 79% males, with a mean age of 72.2 +/- 6.2 years were treated with 100% procedural success. Isolated aortic arch aneurysm was the principle pathology in 17 (60.7%) of patients, while chronic aortic dissection was the principle pathology in 6 (21.4%) of patients. The remaining 5 (17.8%) had combined or other pathologies. At 1 month, the vascular pathology was excluded in 25 of 26 alive patients (96.1%). The 30 days mortality rate was 7.1%, stroke rate was 3.6% (all nondisabling), and combined mortality/stroke rate was 10.7%. One-year mortality was 10.7%, without device or aneurysm-related death. Two patients (7.1%) reported stroke or transient ischemic attack at 1 year that recovered completely. One year combined mortality/stroke rate was 17.8%. There were 3 patients (10.7%) that had device-related unplanned reinterventions through 1 year. Conclusions:The NEXUS Aortic Arch Stent Graft System, a novel single branch, 2 stent graft system used for endovascular aortic arch repair that requires landing in the ascending aorta, demonstrates a high success rate with excellent 1 year safety and performance
International Multicentre Study on the Treatment of Infrarenal Penetrating Aortic Ulcers
No full textObjective: This study aimed to evaluate treatment indications, compare therapeutic approaches, and assess outcomes in patients with infrarenal penetrating aortic ulcers (iPAUs). Methods: This was a retrospective, multicentre, observational study of patients with iPAUs treated between January 2018 and December 2022 across 12 European centres. Treatment strategies included open surgical repair (OSR) and endovascular techniques, including balloon expandable stent grafts (BESGs), covered endovascular reconstruction of the aortic bifurcation (CERAB), and endovascular aortic repair (EVAR) using bifurcated or tube grafts. Primary endpoints were technical success, anatomy dependent graft selection, and safety outcomes. Results: Among 260 patients (mean age 74.2 years, 77.7% male), 96.9% (n = 252) underwent endovascular repair. PAU size was the primary indication in 70.4% of cases. Bifurcated grafts were used in 64.7% (n = 163) and tube grafts in 35.3% (n = 89). Bifurcated grafts were more frequently selected for patients with larger proximal landing zones (21 ± 3 mm vs. 18 ± 5 mm; p < .001), wider aortic bifurcation diameters (20 ± 5 mm vs. 18 ± 4 mm; p < .001), shorter PAU to bifurcation distances (30 ± 24 mm vs. 41 ± 33 mm; p = .003), and larger PAU base diameters (median 22 mm [interquartile range 16, 30] vs. 18 mm [interquartile range 12, 25]; p < .001). Although few patients underwent OSR, the group had high technical success and no 30 day mortality. Technical success rates were 97.8% for BESGs, 100% for CERAB, and 99.3% for EVAR. Median hospital stay was 4 days. Major adverse events occurred in 3.5%, with a 30 day mortality rate of 1.5% and a re-intervention rate of 8.1%. Chronic obstructive pulmonary disease independently predicted 30 day mortality (odds ratio [OR] 4.063; p = .039) and major adverse events (OR 7.181; p = .035). Over a median follow up of 21.2 months, overall mortality was 19.3% (9.4% aortic related), with a re-intervention rate of 9.9% (9.4% aortic related). Conclusion: Endovascular repair, especially with bifurcated grafts, was the preferred safe approach. CERAB and BESGs were effective in anatomically suitable cases
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