Selenium Deficiency Promotes Dilatation of the Aorta by Increasing Expression and Activity of Vascular Smooth Muscle Cell Derived Matrix Metalloproteinase-2.

OBJECTIVE: Selenium (Se) is a key part of the body's oxidation defence system. However, it is unclear whether Se affects the development of aortic aneurysm (AA). An animal experiment was conducted to clarify the role of Se in AA development. METHODS: C57BL/6N male mice were fed with a Se deficient (Se-D, < 0.05 mg/kg), Se adequate (Se-A, 0.2 mg/kg), or Se supplemented (Se-S, 1 mg/kg) diet for 8 weeks. Subsequently, an AA murine model (Se-D, n = 11; Se-A, n = 12; Se-S, n = 15) was established using angiotensin II (Ang II, 1 mg/kg/min) for four weeks plus ß-aminopropionitrile (BAPN, 1 mg/mL) for the first two weeks. Saline replaced Ang II, and BAPN was removed during the modelling process for sham mice (Se-A, n = 9). To determine whether Se deficiency promoted aortic dilation via matrix metalloproteinase-2 (MMP-2), the non-specific MMP inhibitor doxycycline (Dox, 100 mg/kg/day) was given to Se-D AA mice (n = 7) for two weeks. RESULTS: The maximum aortic diameter in Se-D AA model mice was significantly increased compared with Se-A AA model mice. MMP-2 expression and activity in the aortic media of Se-D AA model mice was significantly increased compared with Se-A AA model mice. A large number of vascular smooth muscle cells (VSMCs) were found aggregating in the media of the non-dilated aorta of Se-D AA model mice, which was completely inhibited by Dox. The percentage of VSMCs in aortic media of Se-D AA model mice was significantly higher than in Se-A AA model mice. The maximum aortic diameter and occurrence rate of AA in Se-D AA model mice with Dox were significantly reduced compared with Se-D AA model mice. CONCLUSION: Se deficiency promoted dilatation of the aorta in AA model mice by increasing expression and activity of VSMC derived MMP-2, causing abnormal aggregation and proliferation of VSMCs in aortic media.

Octogenarians fare better under local anesthesia for elective endovascular aortic aneurysm repair.

OBJECTIVE: With an aging patient population, an increasing number of octogenarians are undergoing elective endovascular abdominal aortic aneurysm repair (EVAR) in the United States. Multiple studies have shown that, for the general population, use of local anesthetic (LA) for EVAR is associated with improved short-term and long-term outcomes as compared with performing these operations under general anesthesia (GA). Therefore, this study aimed to study the association of LA for elective EVARs with perioperative outcomes, among octogenarians. METHODS: The Vascular Quality Initiative database (2003-2021) was used to conduct this study. Octogenarians (Aged ≥80 years) were selected and sorted into two study groups: LA (Group I) and GA (Group II). Our primary outcomes were length of stay and mortality. Secondary outcomes included operative time, estimated blood loss, return to operating room, cardiopulmonary complications, and discharge location. RESULTS: Of the 16,398 selected patients, 1197 patients (7.3%) were included in Group I, and 15,201 patients (92.7%) were in Group II. Procedural time was significantly shorter for the LA group (114.6 vs 134.6; P < .001), as was estimated blood loss (152 vs 222 cc; P < .001). Length of stay was significantly shorter (1.8 vs 2.6 days; P < .001), and patients were more likely to be discharged home (LA 88.8% vs GA 86.9%; P = .036) in the LA group. Group I also experienced fewer pulmonary complications; only 0.17% experienced pneumonia and 0.42% required ventilator support compared with 0.64% and 1.02% in Group II, respectively. This finding corresponded to fewer days in the intensive care unit for Group I (0.41 vs 0.69 days; P < .001). No significant difference was seen in 30-day mortality cardiac, renal, or access site-related complications. Return to operating room was also equivocal between the two groups. Multivariate regression analysis confirmed GA was associated with a significantly longer length of stay and significantly higher rates of non-home discharge (adjusted odds ratio [AOR], 1.59; P < .001 and AOR, 1.40; P = .025, respectively). When stratified by the New York Heart Association classification system, classes I, II, III, and IV (1.55; P < .001; 1.26; P = .029; 2.03; P < .001; 4.07; P < .001, respectively) were associated with significantly longer hospital stays. CONCLUSIONS: The use of LA for EVARs in octogenarians is associated with shorter lengths of stay, fewer respiratory complications, and home discharge. These patients also experienced shorter procedure times and less blood loss. There was no statistically significant difference in 30-day mortality, return to operating room, or access-related complications. LA for octogenarians undergoing EVAR should be considered more frequently to shorten hospital stays and decrease complication rates.

Rosmarinic Acid Suppresses Abdominal Aortic Aneurysm Progression in Apolipoprotein E-deficient Mice.

An abdominal aortic aneurysm is a life-threatening cardiovascular disorder caused by dissection and rupture. No effective medicine is currently available for the > 90% of patients whose aneurysms are below the surgical threshold. The present study investigated the impact of rosmarinic acid, salvianolic acid C, or salvianolic acid B on experimental abdominal aortic aneurysms. Abdominal aortic aneurysms were induced in apolipoprotein E-deficient mice via infusion of angiotensin II for 4 wks. Rosmarinic acid, salvianolic acid C, salvianolic acid B, or doxycycline as a positive control was provided daily through intraperitoneal injection. Administration of rosmarinic acid was found to decrease the thickness of the aortic wall, as determined by histopathological assay. Rosmarinic acid also exhibited protection against elastin fragmentation in aortic media and down-regulated cell apoptosis and proliferation in the aortic adventitia. Infiltration of macrophages, T lymphocytes, and neutrophils in aortic aneurysms was found, especially at the aortic adventitia. Rosmarinic acid, salvianolic acid C, or salvianolic acid B inhibited the infiltration on macrophages specifically, but these compounds did not influence T lymphocytes and neutrophils. Expression of matrix metalloproteinase 9 and macrophage migration inhibitory factor significantly increased in aortic aneurysms. Rosmarinic acid and salvianolic acid C decreased the expression of matrix metalloproteinase-9 in media, and rosmarinic acid also tended to reduce migration inhibitory factor expression. Further then, partial least squares-discriminate analysis was used to classify metabolic changes among different treatments. Rosmarinic acid affected most of the metabolites in the biosynthesis of the citrate cycle, fatty acid pathway significantly. Our present study on mice demonstrated that rosmarinic acid inhibited multiple pathological processes, which were the key features important in abdominal aortic aneurysm formation. Further study on rosmarinic acid, the novel candidate for aneurysmal therapy, should be undertaken to determine its potential for clinical use.

Midterm outcomes for 605 patients receiving Endologix AFX or AFX2 Endovascular AAA Systems in an integrated healthcare system.

BACKGROUND: Endologix issued important safety updates for the AFX Endovascular AAA System in 2016 and 2018 owing to the risk of type III endoleaks. Outcomes with these devices are limited to small case series with short-term follow-up. We describe the midterm outcomes for a large cohort of patients who received an Endologix AFX or AFX2 device. STUDY DESIGN: Data from an integrated healthcare system's implant registry, which prospectively monitors all patients after endovascular aortic repair, was used for this descriptive study. Patients undergoing endovascular aortic repair with three AFX System variations (Strata [AFX-S], Duraply [AFX-D], and AFX2 with Duraply [AFX2]) were identified (2011-2017). Crude cumulative event probabilities for endoleak (types I and III), major reintervention, conversion to open, rupture, and mortality (aneurysm related and all cause) were estimated. RESULTS: Among 605 patients, 375 received AFX-S, 197 received AFX-D, and 33 received AFX2. Median follow-up for the cohort was 3.9 (interquartile range, 2.5-5.1) years. The crude 2-year incidence of overall endoleak, any subsequent reintervention or conversion, and mortality was 8.8% (95% confidence interval [CI], 6.3-12.3), 12.0% (95% CI, 9.1-15.9), and 8.8% (95% CI, 6.3-12.2) for AFX-S. Respective estimates for AFX-D were 7.9% (95% CI, 4.8-13.0), 10.6% (95% CI, 6.9-16.1), and 9.7% (95% CI, 6.3-14.7); for AFX2, they were 14.1% (95% CI, 4.7-38.2), 16.2% (95% CI, 6.4-37.7), and 21.2% (95% CI, 10.7-39.4). CONCLUSIONS: The midterm outcomes of a large U.S. patient cohort with an Endologix AFX or AFX2 System demonstrate a concerning rate of adverse postoperative events. Patients with these devices should receive close clinical surveillance to prevent device-related adverse events.

Propensity and impact of autologous platelet rich plasma use in acute type A dissection.

BACKGROUND: Coagulopathy in patients undergoing open repair of acute type A aortic dissection using cardiopulmonary bypass and hypothermic circulatory arrest is a common complication. Autologous platelet rich plasma is an intraoperative blood conservation technique, which has been shown in previous studies to promote hemostasis, leading to a reduction of blood product transfusions during elective aortic surgery. The purpose of this study is to evaluate the effectiveness of autologous platelet rich plasma as a blood conservation technique during open surgical repair of acute type A aortic dissection. METHODS: We reviewed all acute type A aortic dissection cases using hypothermic circulatory arrest, excluding patients presenting in extremis. Perioperative transfusion requirements and clinical outcomes were analyzed. The end points analyzed included early mortality, postoperative stroke, renal dysfunction, prolonged ventilation, coagulopathy, and length of postoperative intensive care unit stay. Parsimonious and saturated propensity scores were calculated for platelet rich plasma use, and all outcomes were propensity adjusted. RESULTS: Between 2003 and 2014, 85 of 391 acute type A aortic dissection repairs used autologous platelet rich plasma. Mean age of patients was 58 ± 15 years, and 70% were male. Obstructive sleep apnea (22% vs 13%, P = .04) and baseline ejection fraction (57% ± 6.7% vs 55% ± 10%; P = .014) were higher in the autologous platelet rich plasma group. Intraoperative propensity-adjusted blood products, 2 units fewer packed red blood cells (P = .001), 4 units fewer fresh-frozen plasma (P = .001), 6 units fewer platelets (P = .001), 1.3 units fewer cell-savers (P = .002), and 5 units fewer cryoprecipitate (P = .001) were significantly reduced by autologous platelet rich plasma use. Significant unadjusted reduction in postoperative reoperation for bleeding (8% vs 17%, P = .046) after autologous platelet rich plasma was reported, although propensity adjustment eliminated significance (P = .079). No difference in stroke, cardiac, or renal complications was observed. Postoperative transfusion needed during the first 3 days was significantly reduced in the autologous platelet rich plasma group: 2 units fewer packed red blood cells (P = .13), 2 units fewer fresh-frozen plasma (P = .018), and 5 units fewer platelets (P = .001), when compared with those without autologous platelet rich plasma. Ventilation time was reduced by 3 days (P = .002), and intensive care length of stay was reduced by 3 days (P = .063) after intraoperative autologous platelet rich plasma use. CONCLUSIONS: The use of autologous platelet rich plasma in patients undergoing open repair of acute type A aortic dissection was associated with a reduction in intraoperative and postoperative blood transfusions, as well as decreased early postoperative morbidity.

A Novel Technique for the Treatment of Type 2 Endoleak After Endovascular Aortic Repair: Sac Embolization with Balloon Occlusion of the Aorta (SEBOA).

PURPOSE: We presented a new method of sac embolization using n-butyl-cyanoacrylate (NBCA) with balloon occlusion of the aorta (SEBOA) that can facilitate decreasing flow rate of the involved branches with the goal of type 2 endoleak resolution after endovascular aortic repair (EVAR). TECHNIQUE: This technique is demonstrated in six patients who required type 2 endoleak treatment including previous technical failure. A transarterial approach was performed in four patients and transabdominal direct puncture in two. Technical success was defined as complete embolization of both involved branches and sac on postoperative CT. Sacography under balloon occlusion of the aorta demonstrated decreased flow rate of the all involved branches in all patients. SEBOA was performed using 25 or 33% of NBCA diluted with lipiodol. Technical success was obtained in 3 of 6 patients, and one major complication was observed with adhesion of NBCA to the microcatheter resulting in foreign body retention. CONCLUSION: SEBOA may help solve the difficulty of type 2 endoleak treatment after EVAR as decreased flow rate of the involved branches under balloon occlusion of the aorta was achieved in all patients. However, protocols regarding concentration of NBCA or using other embolic materials are needed to improve the success rate.

The influence of statins on aortic aneurysm after operation: A retrospective nationwide study.

Aortic aneurysm (AA) is a disease with substantially higher health care costs and very high mortality upon rupture. Statins have a non-lipid-lowering pleiotropic mechanism that may be beneficial for AA in disease progression and improvement of AA patient outcomes. Previous studies have been conducted with some limitations and without considering immortal time bias, lag time, and adherence. The aim of our study was to analyze the effect of statin use on AA postoperation after controlling for these factors.All postoperative patients with a diagnosis of AA in Taiwan from 2004 to 2012 were included from the National Health Insurance Research Database. We excluded patients without computed tomography within 1 year after diagnosis and those who died within 30 days after the operation. We also analyzed the medication, medication possession ratio (MPR), immortal time bias, and lag time. Statin users were defined as those using statins for more than 30 days. Primary composite outcomes included mortality, reoperation for AA and rehospitalization for AA during the study period.Among the whole study population (n = 1633), 199/1633 (12.19%) patients were statin users, while the others (n = 1434) were not. Mortality was higher in statin nonusers than in statin users, with a mortality rate of 40% versus 22.61% (P < .0001). There was no significant difference in reoperation or rehospitalization for AA.Statin use may be beneficial for AA patients in our observational study. Prospective randomized controlled studies are needed to define the effect of statin therapy in this population.

Aortic Aneurysm-associated Disseminated Intravascular Coagulation that Responded Well to a Switch from Warfarin to Rivaroxaban.

We describe a case in which uncontrolled chronic disseminated intravascular coagulation (DIC) caused by an aortic aneurysm that was exacerbated by chemotherapy for lung cancer, showed dramatic improvement when warfarin, which was being administered for atrial fibrillation, was replaced by rivaroxaban, a direct oral anticoagulant (DOAC). The present case is interesting because a DOAC was effective in treating DIC due to an aortic aneurysm, whereas warfarin, another oral anticoagulant, was ineffective. In controlling DIC, it is important to inhibit activated coagulation factors such as thrombin and activated factor X, rather than the coagulation factors, which act as substrates.

Reversal of Vascular Calcification and Aneurysms in a Rat Model Using Dual Targeted Therapy with EDTA- and PGG-Loaded Nanoparticles.

Degeneration of elastic lamina and vascular calcification are common features of vascular pathology such as aortic aneurysms. We tested whether dual therapy with targeted nanoparticles (NPs) can remove mineral deposits (by delivery of a chelating agent, ethylene diamine tetraacetic acid (EDTA)) and restore elastic lamina (by delivery of a polyphenol, pentagalloyl glucose (PGG)) to reverse moderate aneurysm development. EDTA followed by PGG NP delivery led to reduction in macrophage recruitment, matrix metalloproteinase (MMP) activity, elastin degradation and calcification in the aorta as compared to delivery of control blank NPs. Such dual therapy restored vascular elastic lamina and improved vascular function as observed by improvement in circumferential strain. Therefore, dual targeted therapy may be an attractive option to remove mineral deposits and restore healthy arterial structures in moderately developed aneurysms.

Perioperative glutamine supplementation restores disturbed renal arginine synthesis after open aortic surgery: a randomized controlled clinical trial.

Postoperative renal failure is a common complication after open repair of an abdominal aortic aneurysm. The amino acid arginine is formed in the kidneys from its precursor citrulline, and citrulline is formed from glutamine in the intestines. Arginine enhances the function of the immune and cardiovascular systems, which is important for recovery after surgery. We hypothesized that renal arginine production is diminished after ischemia-reperfusion injury caused by clamping of the aorta during open abdominal aortic surgery and that parenteral glutamine supplementation might compensate for this impaired arginine synthesis. This open-label clinical trial randomized patients who underwent clamping of the aorta during open abdominal aortic surgery to receive a perioperative supplement of intravenous alanyl-glutamine (0.5 g·kg(-1)·day(-1); group A, n = 5) or no supplement (group B, n = 5). One day after surgery, stable isotopes and tracer methods were used to analyze the metabolism and conversion of glutamine, citrulline, and arginine. Whole body plasma flux of glutamine, citrulline, and arginine was significantly higher in group A than in group B (glutamine: 391 ± 34 vs. 258 ± 19 µmol·kg(-1)·h(-1), citrulline: 5.7 ± 0.4 vs. 2.8 ± 0.4 µmol·kg(-1)·h(-1), and arginine: 50 ± 4 vs. 26 ± 2 µmol·kg(-1)·h(-1), P < 0.01), as was the synthesis of citrulline from glutamine (4.8 ± 0.7 vs. 1.6 ± 0.3 µmol·kg(-1)·h(-1)), citrulline from arginine (2.3 ± 0.3 vs. 0.96 ± 0.1 µmol·kg(-1)·h(-1)), and arginine from glutamine (7.7 ± 0.4 vs. 2.8 ± 0.2 µmol·kg(-1)·h(-1)), respectively (P < 0.001 for all). In conclusion, the production of citrulline and arginine is severely reduced after clamping during aortic surgery. This study shows that an intravenous supplement of glutamine increases the production of citrulline and arginine and compensates for the inhibitory effect of ischemia-reperfusion injury.

Aortic stent-grafts: Endoleak surveillance.

Endoleaks have been referred to as the "Achilles heel" of endovascular aortic aneurysm repair (EVAR) and are the most common complication of this procedure. An endoleak can maintain a high systemic blood pressure within the aneurysm sac, potentially leading to rupture. Follow-up is therefore mandatory to detect and classify possible endoleaks. Computed tomography (CT) remains the gold standard for follow-up, but provides no hemodynamic information on endoleaks and has the disadvantages of exposing patients to iodine contrast and X-ray radiation. Exposure to radiation could be reduced in various ways, by simplifying the triphasic protocol using dual-energy CT imaging, limiting the amount of radiation per slice using iterative reconstruction, and reducing the follow-up schedule that could be altered to include non-ionizing radiation imaging techniques. Contrast-enhanced ultrasound (CEUS) is an interesting alternative to CT, as is magnetic resonance (MR) imaging that can be used as an alternative or for complementary imaging. Long-term follow-up schedules are currently based on repeated CT. However, more recently alternative follow-up protocols have been proposed for patients with no endoleaks nor increase in aneurysmal sac size. These new protocols consist of CT imaging at 1month and 1year after treatment, subsequently followed by CEUS. Nevertheless, the mechanical structure of the stent-graft must still be verified by CT. The use of patient-specific risk-adjusted follow-up protocols, based on preoperative imaging and the first postoperative results, is gradually becoming more and more widespread.

[Aortic inflammatory lesions in Behçet's disease]. / Atteintes aortiques inflammatoires associées à la maladie de Behçet.

The arterial lesions affect about 10% of patients with Behçet's disease (BD). Aortic inflammatory involvement includes predominantly aortic aneurysmal lesions affecting most often the abdominal aorta. They account for the severity of the disease and are a leading cause of death when they hit the aorta or pulmonary arteries. Within the arterial lesions of BD, aortic involvement is, with femoral lesions, the most common site involved (18-28% of patients with vascular disease). Unlike other large vessels vasculitis (i.e. giant cell arteritis and Takayasu's arteritis) diffuse aortitis is observed in less than 5% of patients with BD. Aortic lesions of BD may be asymptomatic (systematic imaging or occasionally associated with other vascular event) or be revealed by the occurrence of abdominal, thoracic or lumbar pain, or an aortic valve insufficiency. Fever is frequently associated. Increase in acute phase reactants is common in these patients. Histological analysis may show infiltration by lymphocytes, neutrophils and plasma cells in the media and adventitia and a proliferation of the vasa vasorum in the media as well as a fibroblastic proliferation. In the later phase, a fibrous thickening of the media and adventitia is observed as well as a proliferation and thickening of the vasa vasorum. The therapeutic management should always include a medical treatment for the control of inflammation (corticosteroids, immunosuppressive drugs and/or biotherapy) and often an endovascular or surgical treatment if the aneurysm is threatening. The choice between endovascular or surgical treatment is considered case by case, depending on the experience of the team, anatomical conditions and of the clinical presentation. In this review, we provide a detailed and updated review of the literature to describe the aortic inflammatory damage associated with Behçet's disease.

Oral surgery under local anesthesia with dexmedetomidine sedation in a morbidly obese patient with aortic dissection

We report a case of a morbidly obese man with an aortic aneurysm, in whom dental surgery was performed before elective cardiac surgery. His aortic aneurysm required emergency surgery. However, because of his morbid obesity, elective cardiac surgery was planned. Considering the high risk of infective endocarditis, dental surgery was required. Our patient was at a high risk of aortic rupture caused by hypertension and breathing difficulty in the supine position. Dexmedetomidine (DEX) is an anti-anxiety, sedative, and analgesic medicine that can stabilize circulatory dynamics and minimize blood pressure fluctuations. We administered intravenous DEX for sedation of the patient in Fowler's position. In conclusion, our understanding of the risk factors of DEX enabled us to perform safe invasive oral treatment.

Bone marrow from blotchy mice is dispensable to regulate blood copper and aortic pathologies but required for inflammatory mediator production in LDLR-deficient mice during chronic angiotensin II infusion.

BACKGROUND: The blotchy mouse caused by mutations of ATP7A develops low blood copper and aortic aneurysm and rupture. Although the aortic pathologies are believed primarily due to congenital copper deficiencies in connective tissue, perinatal copper supplementation does not produce significant therapeutic effects, hinting additional mechanisms in the symptom development, such as an independent effect of the ATP7A mutations during adulthood. METHODS: We investigated if bone marrow from blotchy mice contributes to these symptoms. For these experiments, bone marrow from blotchy mice (blotchy marrow group) and healthy littermate controls (control marrow group) was used to reconstitute recipient mice (irradiated male low-density lipoprotein receptor -/- mice), which were then infused with angiotensin II (1,000 ng/kg/min) for 4 weeks. RESULTS: By using Mann-Whitney U test, our results showed that there was no significant difference in the copper concentrations in plasma and hematopoietic cells between these 2 groups. And plasma level of triglycerides was significantly reduced in blotchy marrow group compared with that in control marrow group (P < 0.05), whereas there were no significant differences in cholesterol and phospholipids between these 2 groups. Furthermore, a bead-based multiplex immunoassay showed that macrophage inflammatory protein (MIP)-1ß, monocyte chemotactic protein (MCP)-1, MCP-3, MCP-5, tissue inhibitor of metalloproteinases (TIMP)-1, and vascular endothelial growth factor (VEGF)-A production was significantly reduced in the plasma of blotchy marrow group compared with that in control marrow group (P < 0.05). More important, although angiotensin II infusion increased maximal external aortic diameters in thoracic and abdominal segments, there was no significant difference in the aortic diameters between these 2 groups. Furthermore, aortic ruptures, including transmural breaks of the elastic laminae in the abdominal segment and lethal rupture in the thoracic segment, were observed in blotchy marrow group but not in control marrow group; however, there was no significant difference in the incidence of aortic ruptures between these 2 groups (P = 0.10; Fisher's exact test). CONCLUSIONS: Overall, our study indicated that the effect of bone marrow from blotchy mice during adulthood is dispensable in the regulation of blood copper, plasma cholesterol and phospholipids levels, and aortic pathologies, but contributes to a reduction of MIP-1ß, MCP-1, MCP-3, MCP-5, TIMP-1, and VEGF-A production and triglycerides concentration in plasma. Our study also hints that bone marrow transplantation cannot serve as an independent treatment option.

Mechanisms of aortic aneurysm formation: translating preclinical studies into clinical therapies.

Aneurysms are common in the abdominal and thoracic regions of the aorta. While generally asymptomatic, progression of aneurysms is associated with the devastating consequences of aortic rupture. Current therapeutic options to prevent rupture are restricted to surgical repair, as there remains a lack of validated pharmaceutical approaches. Absence of proven medical therapies may be a consequence of the paucity of knowledge on mechanisms of aneurysmal initiation, progression and rupture. Many potential therapeutic targets have been identified in several widely used animal models of these diseases. A small number of these targets are currently under clinical evaluation, while many more are in preclinical stages of evaluation. The purpose of this review is to: (1) overview current understanding of mechanisms of aneurysmal initiation and progression and (2) summarise medical therapies that have been investigated clinically, as well as highlight future therapeutic targets.

Aortic dilatation and dissection in Turner syndrome: what we know, what we are unclear about and what we should do in clinical practice?

Aortic dilatation and aortic dissection are increasingly recognised in patients with Turner syndrome (TS). Risk factors for aortic dissection include aortic dilatation, bicuspid aortic valves, coarctation of aorta and pregnancy. The risk of death due to aortic dissection in pregnancy in TS is 2%, which is approximately 100 times higher than the general population, as maternal mortality is extremely low. Ongoing cardiovascular monitoring is recommended, although there remain several unanswered questions in relation to cardiovascular imaging especially the choice of modality for detection of vascular, valvular abnormalities and measurements of aortic dimensions. Due to the relative short stature of patients with TS, aortic dimensions need to be defined by aortic measurements adjusted for body surface area, known as aortic sized index (ASI). The relationship of ASI and other risk factors with aortic dissection is only beginning to be clarified. Clinical management and monitoring of such patients should be delivered by a group of clinicians familiar with the issues unique to TS patients in a multidisciplinary fashion. All clinicians including the non-specialists need to have a low threshold of suspecting aortic dissection in these adolescents and young adults. This up to date review, including a summary of all 122 published cases of TS patients with aortic dissection, aims to provide a summary of recent publications on characteristics of aortic dissection and aortic dilatation in TS to highlight gaps in knowledge and propose possible clinical monitoring pathway of cardiovascular health in children and adults with TS. Cardiovascular assessment and risk counselling is especially crucial during the period of transition of adolescents with TS, although life long monitoring by expert cognizant to the issues specific in TS is essential.

Salvianolic acid A, a matrix metalloproteinase-9 inhibitor of Salvia miltiorrhiza, attenuates aortic aneurysm formation in apolipoprotein E-deficient mice.

Aortic aneurysm (AA) is a life-threatening vascular disease in defect of effective pharmaceutical therapy. Matrix metalloproteinase-9 (MMP-9) is implicated in the development of chronic vascular diseases including aneurysm, but the effective MMP-9 inhibitors are far from development. To develop new candidate for AA therapy, we evaluated the efficiency of salvianolic acid A (SalA), a novel MMP-9 inhibitor, on AA progression in a mouse model and characterized the mechanism of action. SalA is a water soluble compound of the herbal drug Rhizoma Salviae miltiorrhizae (Danshen) which in China is widely used for the treatment of hypertension, coronary artery diseases and myocardial infarction. MMPs activity was evaluated by enzyme kinetic analysis in vitro and in-gel gelatin zymography in vivo. SalA showed selectivity on gelatinase (MMP-2 and MMP-9) than on collagenase (MMP-8 and MMP-13) in vitro, and specificity on MMP-9 than MMP-2 in vivo. Aortic aneurysm was induced by angiotension II (AngII) in apolipoprotein E-deficient (ApoE(-/-)) mice. Aortic structure was evaluated by hematoxylin and eosin, picrosirius red, orein stain. Macrophage infiltration was detected by immunohistochemistry in vivo and transwell in vitro. Comparing with doxycycline (Dox), a well-known MMPs inhibitor, SalA showed similar efficiency against AA progression. SalA significantly decreased aortic diameter and aneurysm severity, ameliorated integrity of vascular structure, inhibited elastin fragmentation and macrophage infiltration. Furthermore, SalA showed greater safety than Dox based on hepatotoxicity evaluation. Our results demonstrated that SalA held great potential for AA therapy.

Acute aortic dissection in a patient receiving multiple tyrosine kinase inhibitors for 5 years.

A 48-year-old male presented with para-aortic lymph node metastases after surgical resection of a clear cell renal cell carcinoma. After first-line treatment with interferon alpha-2b, he was started on pazopanib and lapatinib. Blood pressure was well controlled with temocapril and amlodipine. Treatment had to be stopped 4 years and 8 months after initiation due to overt proteinuria. Then, sunitinib was started as third-line treatment. During the second cycle of sunitinib, he died due to a Stanford type A aortic dissection. Acute aortic dissection could be an adverse event associated with the long-term use of antiangiogenic tyrosine kinase inhibitors.

Polymerase delta interacting protein 2 sustains vascular structure and function.

OBJECTIVE: On the basis of previous evidence that polymerase delta interacting protein 2 (Poldip2) increases reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (Nox4) activity in vascular smooth muscle cells, we hypothesized that in vivo knockdown of Poldip2 would inhibit reactive oxygen species production and alter vascular function. APPROACH AND RESULTS: Because homozygous Poldip2 deletion is lethal, Poldip2(+/-) mice were used. Poldip2 mRNA and protein levels were reduced by ≈50% in Poldip2(+/-) aorta, with no change in p22phox, Nox1, Nox2, and Nox4 mRNAs. NADPH oxidase activity was also inhibited in Poldip2(+/-) tissue. Isolated aortas from Poldip2(+/-) mice demonstrated impaired phenylephrine and potassium chloride-induced contractions, increased stiffness, and reduced compliance associated with disruption of elastic lamellae and excessive extracellular matrix deposition. Collagen I secretion was elevated in cultured vascular smooth muscle cells from Poldip2(+/-) mice and restored by H2O2 supplementation, suggesting that this novel function of Poldip2 is mediated by reactive oxygen species. Furthermore, Poldip2(+/-) mice were protected against aortic dilatation in a model of experimental aneurysm, an effect consistent with increased collagen secretion. CONCLUSIONS: Poldip2 knockdown reduces H2O2 production in vivo, leading to increases in extracellular matrix, greater vascular stiffness, and impaired agonist-mediated contraction. Thus, unaltered expression of Poldip2 is necessary for vascular integrity and function.