Aortic Segments Research Articles

МОРФОЛОГИЧЕСКАЯ ОЦЕНКА ПРОЦЕССА ФОРМИРОВАНИЯ НЕОИНТИМЫ И VASA VASORUM ПОСЛЕ ПРОТЕЗИРОВАНИЯ БРЮШНОЙ АОРТЫ В ЭКСПЕРИМЕНТЕ

Background. The article considers one of the most important problems in modern vascular surgery – the choice of a vascular graft for performing reconstructive surgical operations on the great vessels. The aim of this study is to perform a morphological comparison of the neointima and vasa vasorum formation in an experiment using various types of vascular grafts. Material and methods. The study was performed on female white pigs (n=12). The animals were divided into 2 groups: group 1 – those with implantation of a synthetic vascular graft made of Dacron coated with modified gelatin, group 2 – those with implantation of a biological vascular graft made of bovine xenopericardium. The material for histological examination was explanted vascular grafts with segments of the abdominal aorta. The sections were stained with hematoxylin and eosin, and Masson trichrome. For the morphometric study we used digital images of histological preparations obtained from a Leica DFC425 digital camera as well as scanned digital images of histological preparations obtained from a Leica Aperio AT2 scanner. Results. Morphometric examination of the neointima revealed that 3 and 6 months after surgery, the thickness of the neointima when using a synthetic vascular graft was significantly greater than when using a biological vascular graft from bovine xenopericardium (p<0.001). Endothelization of the neointima was noted only in the group of animals with a bioprosthesis. At the same time, an earlier and more pronounced formation of vasa vasorum was noted in animals with an implanted biological vascular graft. Conclusion. The formation of neointima was noted when using both biological and synthetic vascular grafts. In the group of animals with an implanted biological vascular graft from bovine xenopericardium, neointima endothelization and pronounced vascularization were noted, which indicates a greater physiological potential of this graft and is a factor reducing the risk of thrombosis.

Abstract P195: Vascular MAPK/ERK Activation in sFTL-1-Induced Preeclampsia In Vivo

Vascular endothelial growth factor (VEGF) inhibition is linked to the development of hypertension and proteinuria in preeclampsia. This occurs as anti-angiogenic factors from the placenta contribute to pregnancy-related hypertension disorder. Soluble VEGF receptor fms-like tyrosine kinase-1 (sFLT-1) is an anti-angiogenic factor that counteracts VEGF. Levels of sFLT-1 are three times higher in preeclamptic placentas compared to those from normotensive pregnancies, and plasma sFLT-1 levels increase with the severity of preeclampsia. Infusing sFLT-1 in rodents induces hypertension, proteinuria, and glomerular endotheliosis, resembling the human condition of preeclampsia. Currently, there is no effective pharmacological treatment of preeclampsia, and in severe cases, early delivery is often the only effective treatment. In this study, we aim to determine how sFLT-1 exposure affects the activation of the vascular MAPK/ERK pathway and the contractility of the aorta ex-vivo using wire myography, to assess if the MAPK/ERK pathway can be a therapeutic target in preeclampsia. To this end, we treated pregnant female C57BL/6 mice from embryonic day E7.5 to E18.5 with either sFLT-1 (3.7mg/kg/day) or vehicle (phosphate-buffered saline) delivered by osmotic minipumps (intraperitoneal) and carried out non-invasive tail-cuff blood pressure measurements. After sacrifice, we isolated descending thoracic aorta for isometric tension measurements in a wire myograph. Infusion of sFLT-1 resulted in marked systolic blood pressure (SBP) elevation (D increase of 14 mmHg, P=0.0003) and augmented aortic phosphorylated-ERK activation (2-fold increase, P=0.040) by western blot and displayed impaired acetylcholine-induced endothelial relaxation in thoracic aortic segments (P<0.05), providing in vivo evidence of increased vascular p-ERK activation, accompanied by higher SBP and endothelial dysfunction in sFLT-1 - indued mouse model of preeclampsia. Future experiments are aimed to test the effect of pharmacological ERK inhibition in sFLT-1 infusion in vivo . We hypothesize that sFLT-1-induced rise in SBP and vascular p-ERK could be prevented in vivo by treatment with the pharmacological ERK inhibitor.

Sex-related differences in the clinical course of aortic root and ascending aortic aneurysms: the DisSEXion Study.

To explore male-female differences in aneurysm growth and clinical outcomes in a two-centre retrospective Dutch cohort study of adult patients with ascending aortic aneurysm (AscAA). Adult patients in whom imaging of an AscAA (root and/or ascending: ≥40 mm) was performed between 2007 and 2022 were included. Aneurysm growth was analysed using repeated measurements at the sinuses of Valsalva (SoV) and tubular ascending aorta. Male-female differences were explored in presentation, aneurysm characteristics, treatment strategy, survival, and clinical outcomes. One thousand eight hundred and fifty-eight patients were included (31.6% female). Median age at diagnosis was 65.4 years (interquartile range: 53.4-71.7) for females and 59.0 years (interquartile range: 49.3-68.0) for males (P < .001). At diagnosis, females more often had tubular ascending aortic involvement (75.5% vs. 70.2%; P = .030) while males more often had SoV involvement (42.8% vs. 21.6%; P < .001). Maximum absolute aortic diameter, at any location, at diagnosis did not differ between females (45.0 mm) and males (46.5 mm; P = .388). In females, tubular ascending growth was faster (P < .001), whereas in males, SoV growth was faster (P = .005), corrected for covariates. Unadjusted 10-year survival was 72.5% [95% confidence interval (CI) 67.8%-77.6%] for females and 78.3% (95% CI 75.3%-81.3%) for males (P = .010). Twenty-three type A dissections occurred, with an incidence rate of 8.2/1000 patient-years (95% CI 4.4-14.1) in females and 2.4/1000 patient-years (95% CI 1.2-4.5) in males [incidence rate ratio females/males: 3.4 (95% CI 1.5-8.0; P = .004)]. In patients having entered a diagnostic programme, involvement of aortic segments and age- and segment-related growth patterns differ between women and men with AscAA, particularly at an older age. Unravelling of these intertwined observations will provide a deeper understanding of AscAA progression and outcome in women and men and can be used as an evidence base for patient-tailored clinical guideline development.

Minimizing the landing zone of complex aortic repair using a physician-modified endograft to preserve a prominent Adamkiewicz artery

AbstractThere are increasing number of clinical cases with physician-modified endograft (PMEG) endograft for urgent reconstruction of large pararenal aneurysms to reduce the perioperative complication risks of fragile patients, but the risk of spinal cord ischemia due to the coverage of longer segment of thoracic aorta is relatively high.We demonstrate an expedited endovascular treatment of an 88 mm pararenal aneurysm by performing a 4-vessel fenestrated endovascular aortic repair. A prominent Adamkiewicz artery, ectatic supraceliac aortic segment, median arcuate ligament compression of the celiac artery and severe tortuosity of the common iliac arteries made the endovascular repair more challenging. A PMEG was implanted with simultaneous deployment technique to achieve a short proximal landing zone to preserve the Adamkiewicz artery.The proper risk assessment and preparation of the patient based on the clinical evaluation and procedure planning is essential for the clinical success of PMEG in urgent indication.

Percutaneous Repair of Chronic Aortic Pseudoaneurysm: A Single-Center Experience

BackgroundAortic pseudoaneurysm (AP) is a late complication of aortic repair that, without intervention, carries a high mortality rate. Surgical repair has significant in-hospital mortality and high health care costs. Endovascular stent grafting use is currently limited to branch-free aortic segments or the use of complex fenestrated devices. Our objective was to review the literature and share our institution’s experience with AP percutaneous closure by vascular plugs and occluder technology. MethodsWe retrospectively reviewed percutaneous AP closure cases published in the literature (2005-2016) and from our institution (2017-2019). The follow-up strategy in our institution group was up to the discretion of the performing physician. We measured the procedure’s safety, complications, and follow-up outcomes. ResultsWe found 40 cases in the literature and 10 at our institution. The procedural success rate was 90% in the literature and 100% in our group. Our group’s average length of stay was 1.9 days with no observed major procedural complications. The literature’s follow-up was generally limited to the hospitalization period. Our patients had a median follow-up time of 12 months (range 3-47 months). Late follow-up of AP demonstrated that sac size remained stable or reduced in 6 patients, but a size increase was observed in 4 patients requiring surgical intervention. Death from nonprocedure-related complications occurred in 40% of our patients. The cost per procedure was hypothetically less than for performing open surgical repair. ConclusionsOur experience shows a viable option for percutaneous AP repair, given its initial safety and cost-effectiveness. Our experience highlights the critical role of follow-up imaging in identifying AP expansion and the need for further intervention. The high nonaorta-related mortality seen in follow-up emphasizes the high-risk nature of the population due to comorbidities.

Unravelling the impact of active and passive contributors to arterial stiffness in male mice and their role in vascular aging

Arterial stiffness, a key indicator of vascular health, encompassing active (vascular tone) and passive (extracellular matrix) components. This study aims to address how these different components affect arterial stiffness along the aorta and the influence of aging. Aortic segments of 12 week and 24 month old (both n = 6) male C57BL/6J mice were mounted in a Rodent Oscillatory Set-up to study Arterial Compliance, in order to measure arterial stiffness and vascular reactivity. Regional variations in arterial stiffness were evident, with abdominal infrarenal aorta (AIA) exhibiting highest stiffness and smallest diameters. AIA displayed both the highest amount of collagen and collagen:elastin ratio. Regional ex vivo vascular reactivity revealed heightened AIA contractions and lowered NO availability. Aging is a significant factor contributing towards vessel remodelling and arterial stiffness. Aging increased arterial stiffness, aortic diameters, collagen content, and reduced VSMC contraction. The results of this study could identify specific regions or mechanisms to target in the development of innovative therapeutic interventions aimed at enhancing overall vascular health.

Differences in endothelial function between patients with Type 1 and Type 2 diabetes: effects of red blood cells and arginase.

The mechanisms underlying endothelial dysfunction in Type 1 and Type 2 diabetes (T1DM and T2DM) are unresolved. The red blood cells (RBCs) with increased arginase activity induce endothelial dysfunction in T2DM, but the implications of RBCs and the role of arginase inhibition in T1DM are unexplored. We aimed to investigate the differences in endothelial function in patients with T1DM and T2DM, with focus on RBCs and arginase. Thirteen patients with T1DM and twenty-six patients with T2DM, matched for HbA1c and sex were included. In vivo endothelium-dependent and -independent vasodilation (EDV and EIDV) were assessed by venous occlusion plethysmography before and after administration of an arginase inhibitor. RBCs were co-incubated with rat aortic segments for 18h followed by evaluation of endothelium-dependent (EDR) and -independent relaxation (EIDR) in isolated organ chambers. In vivo EDV, but not EIDV, was significantly impaired in patients with T2DM compared with patients with T1DM. Arginase inhibition resulted in improved EDV only in T2DM. RBCs from patients with T2DM induced impaired EDR but not EIDR in isolated aortic segments, whereas RBCs from patients with T1DM did not affect EDR nor EIDR. The present study demonstrates markedly impaired EDV in patients with T2DM in comparison with T1DM. In addition, it highlights the divergent roles of RBCs and arginase in mediating endothelial dysfunction in T1DM and T2DM. While endothelial dysfunction is mediated via RBCs and arginase in T2DM, these phenomena are not prominent in T1DM thereby indicating distinct differences in underlying mechanisms.

A Mouse Abdominal Aortic Aneurysm Model by Periadventitial Calcium Chloride and Elastase Infiltration.

Abdominal aortic aneurysm (AAA) is a life-threatening disease associated with high mortality rates. It is characterized by the permanent dilation of the abdominal aorta with at least a 50% increase in arterial diameter. Various animal models of AAA have been introduced to mimic the pathophysiological changes and study the underlying mechanisms of AAA. Among these models, the calcium chloride (CaCl2)- and elastase-induced AAA models are commonly used in mice. However, these methods have certain limitations. Traditional intraluminal porcine pancreatic elastase (PPE) perfusion is associated with high technical difficulty and a high rupture rate, while periadventitial administration of PPE yields inconsistent results. In addition, the CaCl2-induced AAA model lacks human AAA features, such as atherothrombosis and aneurysm rupture. Therefore, the combined application of CaCl2 and PPE has been proposed as an approach to enhance success rates and induce greater diameter increases in AAA animal models. This manuscript presents a comprehensive protocol for establishing a mouse AAA model through periaortic infiltration of PPE and CaCl2 in the infrarenal segment of the abdominal aorta. By following this protocol, we can achieve an AAA formation rate of approximately 90% with technical simplicity and reproducibility. Further ultrasound and histological experiments confirm that this model effectively replicates the morphological and pathological changes observed in human AAA.

A novel hybrid prosthesis for open repair of acute DeBakey type I dissection with malperfusion: Early results from the PERSEVERE trial

BackgroundOutcomes after hemiarch repair for acute DeBakey type I aortic dissection (ADTI) remain unfavorable, with high rates of major adverse events and negative aortic remodeling. The PERSEVERE study evaluates the safety and effectiveness of the AMDS Hybrid prosthesis, a novel bare metal stent, in patients presenting with preoperative malperfusion. MethodsPERSEVERE is a prospective single-arm investigational study conducted at 26 sites in the United States. Ninety-three patients underwent ADTI aortic dissection repair with AMDS implantation. The 30-day primary endpoints are a composite rate of 4 major adverse events and the rate of distal anastomotic new entry tears. The secondary endpoints include aortic remodeling. ResultsClinical malperfusion was documented in 76 patients (82%); only radiographic malperfusion, in 17 (18%). The median follow-up in the 93 patients was 5.6 months. Within 30 days, 9 patients died (9.7%), 10 patients (10.8%) experienced new disabling stroke, and 18 patients (19.4%) had new-onset renal failure requiring ≥1 dialysis treatment. There were no cases of myocardial infarction. The composite rate of major adverse events (27%) was lower than that reported in the reference cohort (58%). There were no distal anastomotic new entry tears. Technical success was achieved in 99% of patients. Early remodeling indicated total aortic diameter stability, true lumen expansion, and false lumen reduction in the treated aortic segment. ConclusionsEarly results show significant reductions in major adverse events and distal anastomotic new entry tears, successfully meeting both primary endpoints. The technical success rate was high. AMDS can be used safely in patients with ADTI dissection with malperfusion.

The "Pre-Rotating Dilator Technique" for Optimal Endograft Orientation in Complex Endovascular Aortic Repair.

To describe a novel technique for optimal orientation and accurate deployment of aortic endografts during complex endovascular aortic repair (cEVAR). After establishing the femoral access in the standard fashion, a long large-bore dilator is inserted before the cEVAR delivery system. The dilator is advanced beyond the renovisceral segment noticing the degree of axial rotation. The endograft markers are verified with fluoroscopy outside the patient in the standard way. Thereafter, the cEVAR delivery system is pre-emptively rotated by the same degree in the opposite direction than the dilator showed upon insertion. The endograft is then advanced into position with the markers ending with the markers roughly in position. Minor adjustments are done before and during deployment if needed as per standard technique. The use of long, large-bore dilator before the introduction of the aortic graft allows to proactively minimize the risk of endograft misalignment and malrotation especially in cases with challenging anatomies in both the visceral and iliac segments. This can potentially be used in all cases because it minimizes the manipulation of the delivery system and potentially increases the accuracy of endograft deployment. This report describes a novel technique involving the use of a long large-bore dilator to predict the degree of rotation of the cEVAR delivery system during insertion and thereby enabling a pre-emptive compensation. This facilitates the precise orientation of the main aortic endograft with an easier alignment of any branches and/or fenestrations to their respective target arteries. This approach holds the potential to mitigate several of the difficulties commonly encountered with current cEVAR solutions, especially the challenges posed by small and tortuous access and severe angulation in the iliac and visceral aortic segment.

Advanced Abdominal Aortic Aneurysm Modeling in Mice by Combination of Topical Elastase and Oral ß-aminopropionitrile.

The topical elastase murine model of abdominal aortic aneurysm (AAA) is enhanced when combined with ß-aminopropionitrile (BAPN)-supplemented drinking water to reliably produce true infrarenal aneurysms with behaviors that mimic human AAAs. Topically applying elastase to the adventitia of the infrarenal aorta causes structural damage to the elastic layers of the aortic wall and initiates aneurysmal dilation. Co-administering BAPN, a lysyl oxidase inhibitor, promotes sustained wall degeneration by reducing collagen and elastin crosslinking. This combination results in large AAAs that progressively expand, form intraluminal thrombus, and are capable of rupture. Refining surgical techniques, such as circumferentially isolating the entire infrarenal aortic segment, can help standardize the procedure for a consistent and thorough application of porcine pancreatic elastase despite different operators and anatomic variations between mice. Therefore, the elastase/BAPN model is a refined approach to surgically inducing AAA in mice, which may better recapitulate human aneurysms and provide additional opportunities to study aneurysm growth and rupture risk.

ADAR1 Is Essential for Smooth Muscle Homeostasis and Vascular Integrity.

Vascular smooth muscle cells (VSMCs) play a critical role in maintaining vascular integrity. VSMC dysfunction leads to numerous vascular diseases. Adenosine deaminases acting on RNA 1 (ADAR1), an RNA editing enzyme, has shown both RNA editing and non-editing functions. Global deletion of ADAR1 causes embryonic lethality, but the phenotype of homozygous ADAR1 deletion specifically in SMCs (ADAR1sm-/-) remains to be determined. By crossing ADAR1fl/fl mice with Myh11-CreERT2 mice followed by Tamoxifen induction, we found that ADAR1sm-/- leads to lethality in adult mice 14 days after the induction. Gross examination revealed extensive hemorrhage and detrimental vascular damage in different organs. Histological analyses revealed destruction of artery structural integrity with detachment of elastin laminae from VSMCs in ADAR1sm-/- aortas. Furthermore, ADAR1sm-/- resulted in severe VSMC apoptosis and mitochondrial dysfunction. RNA sequencing analyses of ADAR1sm-/- aorta segments demonstrated profound transcriptional alteration of genes impacting vascular health including a decrease in fibrillin-1 expression. More importantly, ADAR1sm-/- disrupts the elastin and fibrillin-1 interaction, a molecular event essential for artery structure. Our results indicate that ADAR1 plays a critical role in maintaining SMC survival and vascular stability and resilience.

Vasorelaxant and Hypotensive Effects of Galla chinensis in Rats.

Previous studies have revealed the medicinal and therapeutic effects of Galla chinensis. However, no studies have focused on the antihypertensive effects of G. chinensis. Therefore, we aimed to determine the vasorelaxant and hypotensive effects of G. chinensis 50% ethanolic extract (GCE). To evaluate the vascular relaxing effect of GCE, experiments were conducted using aortic segments dissected from Sprague Dawley rats. GCE showed a vasorelaxant effect via the nitric oxide/cyclic guanosine 3',5'-monophosphate pathway, inhibiting Ca2+ channels, and activating K+ channels. The hypotensive effects of GCE were evaluated in spontaneously hypertensive rats (SHRs). The SHRs were randomly divided into a control group and orally administered GCE group (100 or 300 mg/kg). The systolic and diastolic blood pressure decreased significantly by -19.47 ± 4.58% and -31.14 ± 7.66% in the GCE 100 mg/kg group, and -21.64 ± 2.40% and -31.91 ± 5.75% in the GCE 300 mg/kg group at 4 h after administration. Considering its vasorelaxant and hypotensive effects, our results indicate that GCE may be a valuable solution for the control of hypertension. However, further studies on the long-term administration and toxicity of GCE are required.

Association of aortic diameters and mortality in the general population-an MRI-based study.

Increased diameters of the aorta are associated with increased mortality risk. In the present analyses, we assessed whether aortic diameters are associated with cardiovascular and all-cause mortality in community-dwelling individuals free of known cardiovascular disease (CVD). MRI-derived vascular parameters of the thoracic and abdominal aorta from 2668 participants (median age = 53 years; 51.1% women) of the population-based SHIP-START-2 and SHIP-TREND-0 cohorts without CVD were analyzed. Age- and sex-adjusted, as well as multivariable-adjusted Cox-proportional hazard models, were used to estimate associations of diameters of six different aortic segments to mortality. Over a median follow-up time of 10.6 years (IQR: 8.7; 12.4), a total of 188 participants (126 men and 62 women) died, of which 38 deaths were due to CVD. In unadjusted models, mortality rates were higher in participants with aortic diameters above the median compared to below the median for all investigated aortic sections (all log-rank p < 0.001). In multivariable-adjusted models, the diameters of the ascending thoracic aorta (HR = 1.34 95% CI: 1.04; 1.72, p = 0.022) and of the infrarenal aorta (HR = 3.75 95% CI: 1.06; 13.3, p = 0.040), modeled continuously, were associated with greater cardiovascular mortality. The diameter of the subphrenic aorta was associated with higher cardiovascular mortality only in the age and sex-adjusted model (HR = 3.65 95% CI: 1.01; 13.3, p = 0.049). None of the investigated aortic segments were associated with all-cause mortality. Non-indexed diameters of the ascending thoracic and infrarenal aorta were associated with higher cardiovascular mortality but not with all-cause mortality in a population sample free of clinically overt CVD at baseline. Increased aortic diameter is associated with cardiovascular mortality and can help to identify high-risk patients. Increased aortic diameter is associated with mortality. Non-indexed diameters of the ascending and infrarenal aorta are associated with cardiovascular mortality but not all-cause mortality. Aortic diameter measurements support the estimate of cardiovascular mortality.

NADPH oxidase 4-derived hydrogen peroxide counterbalances testosterone-induced endothelial dysfunction and migration.

High levels of testosterone (Testo) are associated with cardiovascular risk by increasing reactive oxygen species (ROS) formation. NADPH oxidases (NOX) are the major source of ROS in the vasculature of cardiovascular diseases. NOX4 is a unique isotype, which produces hydrogen peroxide (H2O2), and its participation in cardiovascular biology is controversial. So far, it is unclear whether NOX4 protects from Testo-induced endothelial injury. Thus, we hypothesized that supraphysiological levels of Testo induce endothelial NOX4 expression to attenuate endothelial injury. Human mesenteric vascular endothelial cells (HMECs) and human umbilical vein endothelial cells (HUVEC) were treated with Testo (10-7 M) with or without a NOX4 inhibitor [GLX351322 (10-4 M)] or NOX4 siRNA. In vivo, 10-wk-old C57Bl/6J male mice were treated with Testo (10 mg/kg) for 30 days to study endothelial function. Testo increased mRNA and protein levels of NOX4 in HMECs and HUVECs. Testo increased superoxide anion (O2-) and H2O2 production, which were abolished by NOX1 and NOX4 inhibition, respectively. Testo also attenuated bradykinin-induced NO production, which was further impaired by NOX4 inhibition. In vivo, Testo decreased H2O2 production in aortic segments and triggered endothelial dysfunction [decreased relaxation to acetylcholine (ACh)], which was further impaired by GLX351322 and by a superoxide dismutase and catalase mimetic (EUK134). Finally, Testo led to a dysregulated endothelial cell migration, which was exacerbated by GLX351322. These data indicate that supraphysiological levels of Testo increase the endothelial expression and activity of NOX4 to counterbalance the deleterious effects caused by Testo in endothelial function.NEW & NOTEWORTHY By inducing ROS formation, high levels of testosterone play a major role in the pathogenesis of cardiovascular disease. NOXs are the major sources of ROS in the vasculature of cardiovascular diseases. Herein, we describe a novel compensatory mechanism by showing that NOX4 is a protective oxidant enzyme and counterbalances the deleterious effects of testosterone in endothelial cells by modulating hydrogen peroxide formation.

What is the Optimal Proximal Landing Zone of the Stent Graft in Treatment of Aortic Type B Dissection?

Retrograde type A aortic dissection (RTAD) represents a serious complication of endovascular treatment for type B aortic dissection (TBAD). To avoid RTAD, it is recommended to land the proximal end of the stent graft in a non-dissected aortic segment. In this study, we investigated whether landing in the dissection area increased the number of events at the proximal site. We conducted a retrospective review of endovascular treatments for TBAD at a single institution between 2009 and 2022. Patients were divided into two groups: group A, with a proximal landing zone entirely within the dissected area, and group B, with the proximal extent of the seal zone in the non-dissected area. We evaluated the occurrence of proximal events, including RTAD, and examined long-term outcomes to assess the validity of landing in the dissection area. The study included eighty-nine patients who underwent endovascular treatment for TBAD. New intimal tears in the proximal landing site occurred in 3 cases (3.4%), with 1 case (2%) in group A and 2 cases (5.1%) in group B, showing no significant difference. Among the three cases, one (1.1%) in group B with zone 2 landing resulted in RTAD. At 60months, the overall survival was 85%, and freedom from aorta-related mortality was 88%, with no significant difference between the groups. Even if the proximal landing is in a dissected area, a treatment strategy performed in zone 3 without proximal landing in zone 2, seeking a non-dissected area, can still provide sufficient therapeutic effects. Level of Evidence 3 Retrospective single-center cohort analysis.

Isoflurane increases the activity of the vascular matrix metalloproteinase-2 in non-pregnant rats and increases the nitric oxide metabolites in pregnancy.

Surgeries that require general anesthesia occur in 1.5-2% of gestations. Isoflurane is frequently used because of its lower possibility of affecting fetal growth. Therefore, we examined the isoflurane anesthesia-induced effects on maternal hemodynamic and vascular changes. We hypothesized that isoflurane would enhance endothelium-dependent vasodilation as a consequence of increased nitric oxide and decreased metalloproteinases (MMPs). Female rats (n=28) were randomized into 4 groups (7 rats/group): conscious (non-anesthetized) non-pregnant group, non-pregnant anesthetized group, conscious pregnant group, and pregnant anesthetized group. Anesthesia was performed on the 20th pregnancy day, and hemodynamic parameters were monitored. Nitric oxide metabolites, gelatinolytic activity of MMP-2 and MMP-9, and the vascular function were assessed. Isoflurane caused no significant hemodynamic changes in pregnant compared with non-pregnant anesthetized group. Impaired acetylcholine-induced relaxations were observed only in conscious non-pregnant group (by approximately 62%) versus 81% for other groups. Phenylephrine-induced contractions were greater in endothelium-removed aorta segments of both pregnant groups (with or without isoflurane) compared with non-pregnant groups. Higher nitric oxide metabolites were observed in anesthetized pregnant in comparison with the other groups. Reductions in the 75 kDa activity and concomitant increases in 64 kDa MMP-2 isoforms were observed in aortas of pregnant anesthetized (or not) groups compared with conscious non-pregnant group. Isoflurane anesthesia shows stable effects on hemodynamic parameters and normal MMP-2 activation in pregnancy. Furthermore, there were increases in nitric oxide bioavailability, suggesting that isoflurane provides protective actions to the endothelium in pregnancy.

Interleukin-10 deficiency induces thoracic perivascular adipose tissue whitening and vascular remodeling.

Perivascular adipose tissue (PVAT) is an adipose layer, surrounding blood vessels, with a local modulatory role. Interleukin-10 (IL-10) has been shown to modulate vascular tissue. This study aimed to characterize the endogenous role of IL-10 in vascular remodeling, and PVAT phenotyping. Thoracic aortic segments from control (C57BL/6J) and IL-10 knockout (IL-10-/-) male mice were used. Analyzes of aorta/PVAT morphometry, and elastin, collagen and reticulin deposition were performed. Tissue uncoupling protein 1 (UCP1) was accessed by Western blotting. Endogenous absence of IL-10 reduced total PVAT area (p = 0.0310), and wall/lumen ratio (p = 0.0024), whereas increased vascular area and thickness (p < 0.0001). Total collagen deposition was augmented in IL-10-/-, but under polarized light, the reduction of collagen-I (p = 0.0075) and the increase of collagen-III (p = 0.0055) was found, simultaneously with reduced elastic fibers deposition (p = 0.0282) and increased deposition of reticular fibers (p < 0.0001). Adipocyte area was augmented in the IL-10 absence (p = 0.0225), and UCP1 expression was reduced (p = 0.0420). Moreover, relative frequency of white adipose cells and connective tissue was augmented in IL-10-/- (p < 0.0001), added to a reduction in brown adipose cells (p < 0.0001). Altogether, these data characterize aorta PVAT from IL-10-/- as a white-like adipocyte phenotype. Endogenous IL-10 prevents vascular remodeling and favors a brown-like adipocyte phenotype, suggesting a modulatory role for IL-10 in PVAT plasticity.

Complement Factor C1q Mediates Vascular Endothelial Dysfunction in STZ-Induced Diabetic Mice.

Diabetes is a significant global public health issue with implications for vascular endothelial cells (ECs) dysfunction and the subsequent development and advancement of diabetic complications. This study aims to compare the cellular and molecular properties of the aorta in normal and streptozotocin (STZ)-induced diabetic mice, with a focus on elucidating potential mechanism underlying EC dysfunction. Here, we performed a single-cell RNA sequencing survey of 32,573 cells from the aorta of normal and STZ-induced diabetic mice. We found a compendium of 10 distinct cell types, mainly ECs, smooth muscle cells (SMCs), fibroblast, pericyte, immune cells and stromal cells. As the diabetes condition progressed, we observed a subpopulation of aortic ECs that exhibited significantly elevated expression of complement (C) molecule C1qa compared to their healthy counterparts. This increased expression of C1qa was found to induce reactive oxygen species (ROS) production, facilitate EC migration and increased permeability, and impair the vasodilation within the aortic segment of mice. Furthermore, AAV-Tie2-shRNA-C1qa was administered into diabetic mice by tail vein injection, showing that inhibition of C1qa in the endothelium led to a reduction in ROS production, decreased vascular permeability, and improved vasodilation. Collectively, these findings highlight the crucial involvement of C1qa in endothelial dysfunction associated with diabetes.

Aortic mineralization triggers the risk of acute type B aortic dissection

Background and aimsThe role of aortic mineralization in the pathogenesis of acute type B aortic dissection (TBAD) is unclear. Whether thoracic aortic calcification (TAC) and circulating alkaline phosphatase (ALP) activity are associated with acute TBAD risk remains elusive. MethodsObservational and Mendelian randomization (MR) studies were conducted sequentially. Using propensity score matching (1:1) by age and sex, patients with acute TBAD (n = 125) were compared with control patients (n = 125). Qualitative (score) and quantitative (volume) analyses of the TAC burden on different thoracic aortic segments were conducted using non-enhanced computed tomography. Univariate and multivariate analyses were used to identify significant independent risk factors for TBAD and TAC burden, respectively. MR was finally used to determine the causal relationship between elevated ALP activity and TBAD risk. ResultsThe qualitative and quantitative analyses revealed that TAC burden was significantly higher in the TBAD group, except for in the ascending aortic segment (both p < 0.05). Preoperative circulating ALP was significantly elevated in the TBAD group (p < 0.001). The elevated TAC burden score on the descending thoracic aortic segment (odds ratio [OR] 3.31, 95% confidence interval [CI] 1.31–8.37) and increased ALP activity (OR 1.03, 95% CI 1.01–1.06) was independently associated with TBAD risk. Interestingly, ALP was significantly positively associated with TAC burden, and MR analyses confirmed that ALP genetically predicted TBAD risk. ConclusionsElevated ALP may trigger TBAD risk via the increased volume of TAC. Aortic mineralization may not protect the aorta itself.