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Background: Optimal antihypertensive medication for chronic type B aortic dissection (AD) remains undecided. This study compared the efficacy and safety of sacubitril/valsartan with valsartan to determine suitable antihypertensive drug combinations., Methods: In this single-center, open-label, randomized, controlled trial, patients with chronic Stanford type B AD and mild hypertension were randomized to receive sacubitril/valsartan 100/200 mg or valsartan 80/160 mg. The primary endpoint was the reduction in mean sitting systolic blood pressure (msSBP) at week 8 in patients with sacubitril/valsartan vs. valsartan. Key secondary endpoints included changes in (i) mean sitting diastolic blood pressure (msDBP); (ii) pulse pressure (PP); and (iii) mean ambulatory blood pressure (BP) for 24-hour, daytime, and nighttime. Safety assessments included adverse events (AEs) and serious AEs. This trial was registered with the Chinese Clinical Trial Registry, identifier: ChiCTR2300073399., Results: A total of 315 patients completed the study. Sacubitril/valsartan provided a significantly greater reduction in msSBP than valsartan at week 8 (between-treatment difference: -5.1 mm Hg [95% confidence interval -5.8 to -4.5], P < 0.001). Reductions in msSBP, msDBP, and PP as well as the mean ambulatory BP for 24-hour, daytime, and nighttime, were significantly greater in sacubitril/valsartan compared with valsartan (all P < 0.001). No excessive episodes of AEs occurred in the sacubitril/valsartan group., Conclusions: Sacubitril/valsartan and valsartan reduced BP compared with baseline values. However, sacubitril/valsartan improved BP control to a greater extent than valsartan. It may offer a new treatment option for patients with mild hypertension and chronic type B AD., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Apoptosis inhibitor of macrophage (AIM) is known to induce apoptosis resistance in macrophages and to exacerbate chronic inflammation, leading to arteriosclerosis. The role of AIM in aortic aneurysm (AA) remains unknown. This study examined the effects of an anti-AIM antibody in preventing AA formation and progression. In apolipoprotein E-deficient mice, AA was induced by subcutaneous angiotensin II infusion. Mice were randomly divided into two groups: (i) AIM group; weekly anti-murine AIM monoclonal antibody injection (n = 10), and (ii) IgG group; anti-murine IgG antibody injection as control (n = 14). The AIM group, compared with the IgG group, exhibited reduced AA enlargement (aortic diameter at 4 weeks: 2.1 vs. 2.7 mm, respectively, p = 0.012); decreased loss of elastic lamellae construction; reduced expression levels of IL-6, TNF-α, and MCP-1; decreased numbers of AIM-positive cells and inflammatory M1 macrophages (AIM: 1.4 vs. 8.0%, respectively, p = 0.004; M1 macrophages: 24.5 vs. 55.7%, respectively, p = 0.017); and higher expression of caspase-3 in the aortic wall (22.8 vs. 10.5%, respectively, p = 0.019). Our results suggest that administration of an anti-AIM antibody mitigated AA progression by alleviating inflammation and promoting M1 macrophage apoptosis., (© 2024. The Author(s).)

Aortic aneurysm is a vascular disease characterized by irreversible vasodilatation that can lead to dissection and rupture of the aortic aneurysm, a life-threatening condition. Thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) are two main types. The typical treatments for aortic aneurysms are open surgery and endovascular aortic repair, which are only indicated for more severe patients. Most patients with aneurysms have an insidious onset and slow progression, and there are no effective drugs to treat this stage. The inability of current animal models to perfectly simulate all the pathophysiological states of human aneurysms may be the key to this issue. Therefore, elucidating the molecular mechanisms of this disease, finding new therapeutic targets, and developing effective drugs to inhibit the development of aneurysms are the main issues of current research. Natural products have been applied for thousands of years to treat cardiovascular disease (CVD) in China and other Asian countries. In recent years, natural products have combined multi-omics, computational biology, and integrated pharmacology to accurately analyze drug components and targets. Therefore, the multi-component and multi-target complexity of natural products have made them a potentially ideal treatment for multifactorial diseases such as aortic aneurysms. Natural products have regained popularity worldwide. This review provides an overview of the known natural products for the treatment of TAA and AAA and searches for potential cardiovascular-targeted natural products that may treat TAA and AAA based on various cellular molecular mechanisms associated with aneurysm development., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Cardiovascular outcome in Marfan syndrome (MFS) patients most prominently depends on aortic aneurysm progression with subsequent aortic dissection. Angiotensin II receptor blockers (ARBs) prevent aneurysm formation in MFS mouse models. In patients, ARBs only slow down aortic dilation. Downstream signalling from the angiotensin II type 1 receptor (AT1R) is mediated by G proteins and β-arrestin recruitment. AT1R also interacts with the monocyte chemoattractant protein-1 (MCP-1) receptor, resulting in inflammation. In this study, we explore the targeting of β-arrestin signalling in MFS mice by administering TRV027. Furthermore, because high doses of the ARB losartan, which has been proven beneficial in MFS, cannot be achieved in humans, we investigate a potential additive effect by combining lower concentrations of losartan (25 mg/kg/day and 5 mg/kg/day) with barbadin, a β-arrestin blocker, and DMX20, a C-C chemokine receptor type 2 (CCR2) blocker. A high dose of losartan (50 mg/kg/day) slowed down aneurysm progression compared to untreated MFS mice (1.73 ± 0.12 vs. 1.96 ± 0.08 mm, p = 0.0033). TRV027, the combination of barbadin with losartan (25 mg/kg/day), and DMX-200 (90 mg/kg/day) with a low dose of losartan (5 mg/kg/day) did not show a significant beneficial effect. Our results confirm that while losartan effectively halts aneurysm formation in Fbn1 C1041G/+ MFS mice, neither TRV027 alone nor any of the other compounds combined with lower doses of losartan demonstrate a notable impact on aneurysm advancement. It appears that complete blockade of AT1R function, achieved by administrating a high dosage of losartan, may be necessary for inhibiting aneurysm progression in MFS.

Aortic aneurysm/dissection (AAD) is a serious cardiovascular condition characterized by rapid onset and high mortality rates. Currently, no effective drug treatment options are known for AAD. AAD pathogenesis is associated with the phenotypic transformation and abnormal proliferation of vascular smooth muscle cells (VSMCs). However, endogenous factors that contribute to AAD progression remain unclear. We aimed to investigate the role of histone deacetylase 9 (HDAC9) in AAD pathogenesis. HDAC9 expression was considerably increased in human thoracic aortic dissection specimens. Using RNA-sequencing (RNA-seq) and chromatin immunoprecipitation, we demonstrated that HDAC9 transcriptionally inhibited the expression of superoxide dismutase 2 and insulin-like growth factor-binding protein-3, which are critically involved in various signaling pathways. Furthermore, HDAC9 triggered the transformation of VSMCs from a systolic to synthetic phenotype, increasing their proliferation and migration abilities and suppressing their apoptosis. Consistent with these results, in vivo experiments revealed that TMP195, a pharmacological inhibitor of HDAC9, suppressed the formation of the β-aminopropionitrile-induced AAD phenotype in mice. Our findings indicate that HDAC9 may be a novel endogenous risk factor that promotes the onset of AAD by mediating the phenotypic transformation of VSMCs. Therefore, HDAC9 may serve as a potential therapeutic target for drug-based AAD treatment. Furthermore, TMP195 holds potential as a therapeutic agent for AAD treatment., Competing Interests: Declaration of Competing Interest Declarations of interest: none, (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Study Objective: The objectives of this study were to (i) quantify the incidence of three concerning fluoroquinolone adverse events of interest (FQAEI, i.e., adverse tendon event (TE), clostridioides difficile infection (CDI), and aortic aneurysm/dissection (AAD)), (ii) identify the patient-level factors that predict these events, and (iii) develop clinical risk scores to estimate the predicted probabilities of each FQAEI based on patient-level covariates available on clinical presentation., Design: Retrospective cohort study., Setting: Upstate New York Veterans' Healthcare Administration from 2011 to 2016., Patients: Hospitalized patients with community-acquired pneumonia receiving care in the Upstate New York Veterans' Healthcare Administration from 2011 to 2016., Intervention: N/A., Measurements: The outcomes of interest for this study were the occurrence of TE, CDI, and AAD. We also evaluated a composite of these three outcomes, FQAEI., Main Results: The study population consisted of 1071 patients. The overall incidence of FQAEI, TE, AAD, and CDI was 6.5%, 1.8%, 4.5%, and 0.3%, respectively. For each outcome evaluated, the probability of the event of interest was predicted by the presence of certain comorbidities, previous healthcare exposure, choice of specific FQ antibiotic, or therapy duration. Concomitant steroids, pneumonia in preceding 180 days, and creatinine clearance <30 mL/min predicted FQAEI., Conclusions: Individual frequencies of three important FQAEIs were quantified, and risk scores were developed to estimate the probabilities of experiencing these events to help clinicians individualize treatment decisions for patients and reduce the potential risks of select FQAEIs., (© 2023 The Authors. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy published by Wiley Periodicals LLC on behalf of Pharmacotherapy Publications, Inc.)

Aortic aneurysm (AA) is a vascular disorder characterized pathologically by inflammatory cell invasion and extracellular matrix (ECM) degradation. It is known that regulation of the balance between pro-inflammatory M1 macrophages (M1Ms) and anti-inflammatory M2 macrophages (M2Ms) plays a pivotal role in AA stabilization. We investigated the effects of M2M administration in an apolipoprotein E-deficient (apoE -/- ) mouse model in which AA was induced by angiotensin II (ATII) infusion. Mice received intraperitoneal administration of 1 million M2Ms 4 weeks after ATII infusion. Compared with a control group that was administered saline, the M2M group exhibited reduced AA expansion; decreased expression levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1); and a lower M1M/M2M ratio. Moreover, the M2M group exhibited upregulation of anti-inflammatory factors, including IL-4 and IL-10. PKH26-labeled M2Ms accounted for 6.5% of cells in the aneurysmal site and co-expressed CD206. Taken together, intraperitoneal administration of M2Ms inhibited AA expansion by reducing the inflammatory reaction via regulating the M1M/M2M ratio. This study shows that M2M administration might be useful for the treatment of AA., (© 2023. The Author(s).)

Takayasu arteritis (TAK) is classified as large vessel vasculitis, and continuous inflammation of the vessel results in aneurysm or stenosis, which leads to various serious complications. Recently, a TAKT [TAK treated with tocilizumab (TCZ)] study showed that subcutaneous TCZ, a humanised anti-interleukin-6 receptor monoclonal antibody, is an effective treatment in patients with TAK above 12 years of age; however, the effectiveness of TCZ for juvenile TAK under 12 years old remains unclear. Here, we described the case of a 2-year-old girl with TAK, which was successfully treated with intravenous TCZ. She was diagnosed with TAK type V (Numano's angiographic classification system) with aortic aneurysms, bilateral renal arteries stenosis, and atypical descending aortic coarctation based on contrast-enhanced computed tomography findings. Treatment was started with 2 mg/kg/day prednisolone (PSL) and methotrexate instead of methylprednisolone pulse due to renovascular hypertension. She was immediately afebrile and her C-reactive protein level decreased, although it was elevated 4 weeks after starting PSL. Intravenous TCZ of 8 mg/kg/2 weeks was added because the progression of aneurysms or stenosis might lead to a poor prognosis. PSL was steadily reduced under intravenous TCZ. Magnetic resonance imaging showed that aortic aneurysms, renal arteries stenosis, and aortic coarctation ameliorated 4 months after starting TCZ, with the amelioration maintained at 1 year after starting TCZ. Aneurysms and stenosis improved; therefore, TCZ may be effective for the treatment of inflammation of vessels, aneurysms, and stenosis. It is desirable to examine the effect of TCZ on TAK patients under 12 years of age., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aortic aneurysms are prevalent and severe vascular diseases with high mortality from unpredicted ruptures, while the only treatment option is surgical correction of large aneurysms with considerable risk. We have shown that folic acid (FA) is highly effective in alleviating development of aneurysms although not sufficient to completely attenuate aneurysm formation. Here, we examined therapeutic effects on aneurysms of combining FA with Nifedipine as novel and potentially more effective oral medication. Oral administration with FA (15 mg/kg/day) significantly reduced incidence of AAA from 85.71% to 18.75% in Ang II-infused apolipoprotein E (apoE) null mice, while combination of FA with Nifedipine (1.5, 5.0 or 20 mg/kg/day) substantially and completely further reduced incidence of AAA to 12.5%, 11.76% and 0.00% respectively in a dose-dependent manner. The combinatory therapy substantially and completely further alleviated enlargement of abdominal aortas defined by ultrasound, vascular remodeling characterized by elastin degradation and adventitial hypertrophy, as well as aortic superoxide production and eNOS uncoupling activity also in a dose-dependent manner, with combination of FA with 20 mg/kg/day Nifedipine attenuating all of these features by 100% to control levels. Aortic NO and H 4 B bioavailabilities were also dose-dependently further improved by combining FA with Nifedipine. These data establish entirely innovative and robust therapeutic regime of FA combined with Nifedipine for the treatment of aortic aneurysms. The comminatory therapy can serve as a first-in-class and most effective oral medication for aortic aneurysms, which can be rapidly translated into clinical practice to revolutionize management of the devastating vascular diseases of aortic aneurysms known as silent killers., (Copyright © 2022. Published by Elsevier B.V.)

Background: Increasing evidence indicates that redox stress participates in MFS aortopathy, though its mechanistic contribution is little known. We reported elevated reactive oxygen species (ROS) formation and NADPH oxidase NOX4 upregulation in MFS patients and mouse aortae. Here we address the contribution of xanthine oxidoreductase (XOR), which catabolizes purines into uric acid and ROS in MFS aortopathy., Methods and Results: In aortic samples from MFS patients, XOR protein expression, revealed by immunohistochemistry, increased in both the tunicae intima and media of the dilated zone. In MFS mice (Fbn1 C1041G/+ ), aortic XOR mRNA transcripts and enzymatic activity of the oxidase form (XO) were augmented in the aorta of 3-month-old mice but not in older animals. The administration of the XOR inhibitor allopurinol (ALO) halted the progression of aortic root aneurysm in MFS mice. ALO administrated before the onset of the aneurysm prevented its subsequent development. ALO also inhibited MFS-associated endothelial dysfunction as well as elastic fiber fragmentation, nuclear translocation of pNRF2 and increased 3'-nitrotyrosine levels, and collagen maturation remodeling, all occurring in the tunica media. ALO reduced the MFS-associated large aortic production of H 2 O 2 , and NOX4 and MMP2 transcriptional overexpression., Conclusions: Allopurinol interferes in aortic aneurysm progression acting as a potent antioxidant. This study strengthens the concept that redox stress is an important determinant of aortic aneurysm formation and progression in MFS and warrants the evaluation of ALO therapy in MFS patients., Competing Interests: Declaration of competing interest None., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Fluoroquinolone (FQ) antibiotics were approved in 1986 for treatment of urinary tract infections, sinusitis, and bronchitis. Numerous putative FQ-associated adverse events have been recently reported., Areas Covered: We review international regulatory agency experience with these FQ-associated toxicities. A 2015 FDA Advisory Committee meeting led regulatory agencies in Canada, Australia, the European Union, New Zealand, and Japan between 2017 and 2021 to evaluate FQ-associated long-term disability and aortic aneurysm/dissections. Regulatory agency guidance in the United States in 2016 warn that FQs should not be used as first-line therapies for urinary tract infections, sinusitis, and bronchitis if other antibiotics are available because of potential long-term and disabling toxicity. Regulatory agencies in European Union countries warn that FQs should not be used to treat mild infections. Product labels in Australia, New Zealand, Japan, and Canada do not have warnings related to FQ-associated disability. Revised product labels and public health advisories in the United States, the European Union, and Japan warn against FQ administration to persons at aortic aneurysm/dissection risks, while product labels and regulatory agency notifications from Canada, Australia, and New Zealand do not include these warnings., Expert Opinion: Harmonization of warnings related to FQ-associated disability in particular should be considered.

Background: Marfan syndrome (MFS) is a genetic disorder leading to medial aortic degeneration and life-limiting dissections. To date, there is no causal prevention or therapy. Rapamycin is a potent and selective inhibitor of the mechanistic target of rapamycin (mTOR) protein kinase, regulating cell growth and metabolism. The mgR/mgR mice represent an accepted MFS model for studying aortic pathologies to understand the underlying molecular pathomechanisms. This study investigated whether rapamycin inhibits the development of thoracic aortic aneurysms and dissections in mgR/mgR mice., Methods: Isolated primary aortic smooth muscle cells (mAoSMCs) from mgR/mgR mice were used for in vitro studies. Two mg kg/BW rapamycin was injected intraperitoneally daily for two weeks, beginning at 7-8 weeks of age. Mice were sacrificed 30 days post-treatment. Histopathological and immunofluorescence analyses were performed using adequate tissue specimens and techniques. Animal survival was evaluated accompanied by periodic echocardiographic examinations of the aorta., Results: The protein level of the phosphorylated ribosomal protein S6 (p-RPS6), a downstream target of mTOR, was significantly increased in the aortic tissue of mgR/mgR mice. In mAoSMCs isolated from these animals, expression of mTOR, p-RPS6, tumour necrosis factor α, matrix metalloproteinase-2 and -9 was significantly suppressed by rapamycin, demonstrating its anti-inflammatory capacity. Short-term rapamycin treatment of Marfan mice was associated with delayed aneurysm formation, medial aortic elastolysis and improved survival., Conclusions: Short-term rapamycin-mediated mTOR inhibition significantly reduces aortic aneurysm formation and thus increases survival in mgR/mgR mice. Our results may offer the first causal treatment option to prevent aortic complications in MFS patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Autophagy is a well-conserved biological process that maintains homeostasis. Accumulating evidence has revealed that autophagy plays an important role in various cardiovascular diseases, such as aneurysm, aortic dissection, atherosclerosis, and myocardial ischemia-reperfusion injury. Here, we summarize the current experimental evidence on the function of autophagy and autophagy proteins in aortic aneurysm and dissection (AAD). AAD is a very serious aortic disease, and there are currently no effective drug treatment options. Studies have shown that autophagy is activated during AAD. However, the role of autophagy in AAD is still controversial. For example, knocking out autophagy related 5 (ATG5) or ATG7 to inhibit autophagy and excessive autophagy activation can promote the occurrence of AAD. Recently, multiple studies have demonstrated that rapamycin and metformin, which are autophagy activators, can delay the progression of AAD. Thus, targeting autophagy has the potential to become a new therapeutic strategy for AAD. In addition, we discuss the recent research progress on AAD from the perspective of single-cell RNA sequencing. Moreover, we offer our perspective on current challenges and barriers in this research field., Competing Interests: Conflict of interest statement The authors declare that they have no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

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., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

In 2018, the U.S. Food and Drug Administration (FDA) issued a Drug Safety Communication regarding fluoroquinolone-associated aortic aneurysm. This quasi-experimental study assessed antibiotic prescribing for 198 patients hospitalized with diabetic foot infection. Following the warning, median inpatient fluoroquinolone days of therapy (DOT) decreased from 3 to 0 days ( P <  0.001), corresponding to increased beta-lactam DOT and outpatient parenteral antimicrobial therapy enrollment. FDA communications may influence antibiotic selection and transitions of care, representing opportunities for antimicrobial stewardship.

Abstract: Aortic aneurysm (AA) remains one of the primary causes of death worldwide. Of the major treatments, prophylactic operative repair is used for AA to avoid potential aortic dissection or rupture. To halt the development of AA and alleviate its progression into aortic dissection, pharmacological treatment has been investigated for years. Currently, β-adrenergic blocking agents, losartan, irbesartan, angiotensin-converting-enzyme inhibitors, statins, antiplatelet agents, doxycycline, and metformin have been investigated as potential candidates for preventing AA progression. However, the paradox between preclinical successes and clinical failures still exists, with no medical therapy currently available for ideally negating the disease progression. This review describes the current drugs used for pharmacological management of AA and their individual potential mechanisms. Preclinical models for drug screening and evaluation are also discussed to gain a better understanding of the underlying pathophysiology and ultimately find new therapeutic targets for AA., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Aortic Z-score (Z-score) is utilized in clinical trials to monitor the effect of medications on aortic dilation rate in Marfan (MFS) patients. Z-scores are reported in relation to body surface area and therefore are a function of height and weight. However, an information void exists regarding natural, non-pharmacological changes in Z-scores as children age. We had concerns that Z-score decrease attributed to "therapeutic" effects of investigational drugs for Marfan disease connective tissue diseases might simply reflect normal changes ("filling out" of body contour) as children age. This investigation studies natural changes with age in Z-score in normal and untreated MFS children, teasing out normal effects that might erroneously be attributed to drug benefit. (1) We first compared body mass index (BMI) and Z-scores (Boston Children's Hospital calculator) in 361 children with "normal" single echo exams in four age ranges (0 to 1, 5 to 7, 10 to 12, 15 to 18 years). Regression analysis revealed that aging itself decreases ascending Z-score, but not root Z-score, and that increase in BMI with aging underlies the decreased Z-scores. (2) Next, we examined Z-score findings in both "normal" and Marfan children (all pharmacologically untreated) as determined on sequential echo exams over time. Of 27 children without aortic disease with sequential echos, 19 (70%) showed a natural decrease in root Z-score and 24 (89%) showed a natural decrease in ascending Z- score, over time. Of 25 untreated MFS children with sequential echos, 12 (40%) showed a natural decrease in root Z-score and 10 (33%) showed a natural decrease in ascending Z-score. Thus, Z-score is over time affected by natural factors even in the absence of any aneurysmal pathology or medical intervention. Specifically, Z-score decreases spontaneously as a natural phenomenon as children age and with fill out their BMI. Untreated Marfan patients often showed a spontaneous decrease in Z-score. In clinical drug trials in aneurysm disease, decreasing Z-score has been interpreted as a sign of beneficial drug effect. These data put such conclusions into doubt., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Infective native aortic aneurysms (INAA) are aneurysms arising from infection of the aortic wall. Treatment is demanding with 5-year survival rates between 53 and 55%. The aim of our study was to evaluate the usefulness of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in the long-term monitoring of patients with proven INAA. Fifty-three PET/CT were performed in 15 patients with INAA in this single-center retrospective cohort study and retrospective analysis of prospectively collected Vascular Graft Cohort Study (VASGRA) data. Median metabolic activity (as measured by maximum standardized uptake value, SUVmax) of the aneurysms at the initial PET/CT was high (6.8 (IQR 5.7-21.8)), and lower at the last PET/CT prior to the end of antimicrobial therapy (3.9 (IQR 2.7-6.8); n = 11) as well as in the first PET/CT after the end of the treatment (3.9 (IQR 3.0-4.4);n = 6). Compared to the course of C-reactive protein alone, PET/CT provided different (> 20% difference in trend) or altering (opposed trend) information on the course of disease in at least 14 comparisons (56%) in 11 patients (73%). The one-year and five-year freedom from all-cause lethality was 92% (95% confidence interval 57%-99%). As compared to the course of C-reactive protein, PET/CT provides different and occasionally altering information in therapy control of INAA.

Introduction: The conservative management of a Stanford type B aortic dissection (TBD) is optimal blood pressure management, cardiac rehabilitation, and progressive return to activities of daily living (ADL) while preventing advancing dissection and aortic dilation. Recent case reports indicate higher levels of activity may be safe; however, the exercise parameters for chronic TBD conditions span a broad range and the research is limited., Case Presentation: The clinical presentation and outpatient cardiac and physical rehabilitation program for a 61-year-old male with a chronic TBD from his subclavian artery to common iliac arteries is presented. The exercise protocol was developed and based on the available literature for the management of chronic aortic diseases. Eighteen months after the patient's acute TBD event, he began an exercise protocol designed to address the sport specific functional deficits related to his recreational activities. The program incorporated a variety of exercises from resistance training to cardiovascular exercise and high interval training. The therapeutic goals included restoration of cardiac fitness and improvement of core stability and appendicular strength, ultimately aiming toward a potential to return to recreational sport involving short duration, high intensity activity., Conclusion: In conjunction with the appropriate anti-hypertensive medication treatment, understanding the concepts of aortic hemodynamics as they relate to exercise can serve as a guideline for clinicians in developing an individualized exercise program for their TBD patients. Moreover, these physical training programs may include particular exercise guidelines beyond general recommendations of light to moderate cardiovascular activities.

Diabetes mellitus (DM) is also a cause of cardiovascular (CV) disease (CVD). Addressing the atherosclerotic CVD (ASCVD) burden in DM should reduce premature death and improve quality of life. Diabetes mellitus-associated ASCVD can lead to complications in all vascular beds (carotids as well as coronary, lower extremity, and renal arteries). This narrative review considers the diagnosis and pharmacological treatment of noncardiac atherosclerotic vascular disease (mainly in patients with DM). Based on current knowledge and the fact that modern DM treatment guidelines are based on CV outcome trials, it should be noted that patients with noncardiac CVD may not have the same benefits from certain drugs compared with patients who predominantly have cardiac complications. This leads to the conclusion that in the future, consideration should be given to conducting well-designed trials that will answer which pharmacological treatment modalities will be of greatest benefit to patients with noncardiac ASCVD.

Atherosclerosis-related acute aortic syndromes, such as aortic aneurysms or aortic dissection are life-threatening diseases. Since they develop suddenly and progress rapidly, the establishment of preventive strategies is urgently needed. Quercetin, a flavonoid abundant in various vegetables and fruits, is suggested to reduce the risk of cardiovascular disease. Therefore, in this study, the preventive effect of quercetin was evaluated using a mouse model of aortic aneurysm and dissection. The model was established by administering angiotensin II (Ang II) and β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, to mice to induce hypertension and degeneration of the elastic lamina, which would eventually result in the onset of an aortic aneurysm. Ang II, BAPN, and a nitric oxide synthase inhibitor was administered to induce aortic dissection via endothelial dysfunction. Quercetin (60 mg/kg/day) was administered 2 weeks before inducing aortic diseases by the end of the experiments (8 weeks in the aneurysm model, 6 weeks in the dissection model). It was found to reduce the incidence of aneurysm (from 72 to 45%), dissection (from 17 to 10%), and rupture (from 33 to 15%) in mice. Elastin degradation was ameliorated in the quercetin-treated mice compared to that in the mice without quercetin treatment (degradation score 2.9 ± 0.3 vs 2.2 ± 0.2). Furthermore, quercetin suppressed the expression of vascular cell adhesion molecule-1, macrophage infiltration, and pro-matrix metalloproteinase-9 activity. Our results suggest that quercetin might prevent the onset of atherosclerosis-related acute aortic syndromes through its anti-inflammatory and endothelial cell-protective effects.

Introduction: Recent studies have raised concerns that fluoroquinolone use is associated with an increased risk of aortopathy, including aortic aneurysm with and without dissection., Objective: We performed a meta-analysis with a comprehensive literature review to further investigate this association., Methods: This analysis was conducted per PRISMA guidelines. PubMed, Cochrane Library, ClinicalTrials.gov, Embase, Web of Science, and Google Scholar were searched for studies that included adult patients (age >18 years) exposed to fluoroquinolones or control antibiotics (amoxicillin/any other antibiotic) for urinary tract infection or pneumonia with a primary outcome of aortic aneurysm or dissection. Heterogeneity was calculated using Q statistic I 2  ., Results: A total of 6 studies-comprised of 59% males-were included in our analysis, which showed an increased combined risk of development of aortic aneurysm and aortic dissection with quinolone exposure when compared with controls (relative risk [RR] = 2.11; 95% CI, 1.62 - 2.75; I 2  = 83.700). Individual relative risk for aortic aneurysm (RR = 2.83; 95% CI, 2.02 - 3.95, I 2   = 89.150) and aortic dissection (RR = 1.99; 95% CI, 1.23 - 3.06; I2 2  = 71.33) also were significantly increased., Conclusion: Compared to other antibiotics, the use of fluoroquinolones was associated with a significantly higher risk of aortic aneurysm and dissection combined., (Copyright© Board of Regents of the University of Wisconsin System and The Medical College of Wisconsin, Inc.)

Aortic structure and function are controlled by the coordinated actions of different aortic cells and the extracellular matrix. Several pathways have been identified that control the aortic wall in a cell-type-specific manner and play diverse roles in various phases of aortic injury, repair, and remodeling. This complexity of signaling in the aortic wall poses challenges to the development of therapeutic strategies for treating aortic aneurysms and dissections. Here, in part II of this Recent Highlights series on aortic aneurysms and dissections, we will summarize recent studies published in Arteriosclerosis, Thrombosis, and Vascular Biology that have contributed to our knowledge of the signaling pathway-related mechanisms of aortic aneurysms and dissections.

Aortic aneurysm is a permanent focal dilation of the aorta. It is usually an asymptomatic disease but can lead to sudden death due to aortic rupture. Aortic aneurysm-related mortalities are estimated at ∼200,000 deaths per year worldwide. Because no pharmacological treatment has been found to be effective so far, surgical repair remains the only treatment for aortic aneurysm. Aortic aneurysm results from changes in the aortic wall structure due to loss of smooth muscle cells and degradation of the extracellular matrix and can form in different regions of the aorta. Research over the past decade has identified novel contributors to aneurysm formation and progression. The present review provides an overview of cellular and noncellular factors as well as enzymes that process extracellular matrix and regulate cellular functions (e.g., matrix metalloproteinases, granzymes, and cathepsins) in the context of aneurysm pathogenesis. An update of clinical trials focusing on therapeutic strategies to slow abdominal aortic aneurysm growth and efforts underway to develop effective pharmacological treatments is also provided.

Atherosclerosis is a lipid-driven chronic inflammatory disease that is modulated by many immune cell subsets, including B cells. Therefore, targeting the inflammatory component of cardiovascular disease represents a promising therapeutic strategy. In the past years, immunotherapy has revolutionized the treatment of autoimmunity and cancer. Many of these clinically used strategies target B cells. Given the multifaceted role of B cells in atherogenesis, it is conceivable that B-cell-directed therapies can modulate disease development. Here, we review clinically available B-cell-targeted therapies and the possible benefits or detrimental effects on cardiovascular disease.

Background: The pathogenesis of abdominal aortic aneurysm (AAA) is characterized by atherosclerosis with chronic inflammation in the aortic wall. Montelukast is a selective cys-LT 1 receptor antagonist that can suppress atherosclerotic diseases. We evaluated the in vitro properties of montelukast and its in vivo activities in an angiotensin II-infused apolipoprotein E-deficient (apoE -/- ) AAA mouse model., Methods: The mouse monocyte/macrophage cell line J774A.1 was used in vitro. M1 macrophages were treated with montelukast, and gene expressions of inflammatory cytokines were measured. Macrophages were cultured with montelukast, then gene expressions of arginase-1 and IL (interleukin)-10 were assessed by quantitative polymerase chain reaction, arginase-1 was measured by fluorescence-activated cell sorting, and IL-10 concentration was analyzed by enzyme-linked immunosorbent assay. In vivo, one group (Mont, n=7) received oral montelukast (10 mg/kg/day) for 28 days, and the other group (Saline, n=7) was given normal Saline as a control for the same period. Aortic diameters, activities of matrix metalloproteinases (MMPs), cytokine concentrations, and the number of M2 macrophages were analyzed., Results: Relative to control, montelukast significantly suppressed gene expressions of MMP-2, MMP-9, and IL-1 β , induced gene expressions of arginase-1 and IL-10, enhanced the expression of the arginase-1 cell surface protein, and increased the protein concentration of IL-10. In vivo, montelukast significantly decreased aortic expansion (Saline vs Mont; 2.44 ± 0.15 mm vs 1.59 ± 0.20 mm, P<.01), reduced MMP-2 activity (Saline vs Mont; 1240 μ M vs 755 μ M, P<.05), and induced infiltration of M2 macrophages (Saline vs Mont; 7.51 % vs 14.7 %, P<.05)., Conclusion: Montelukast induces M2 macrophage polarization and prevents AAA formation in apoE -/- mice.

Aortic aneurysm is the most life-threatening complication in Marfan syndrome (MFS) patients. Doxycycline, a nonselective matrix metalloproteinases inhibitor, was reported to improve the contractile function and elastic fiber structure and organization in a Marfan mouse aorta using ex vivo small chamber myography. In this study, we assessed the hypothesis that a long-term treatment with doxycycline would reduce aortic root growth, improve aortic wall elasticity as measured by pulse wave velocity, and improve the ultrastructure of elastic fiber in the mouse model of MFS. In our study, longitudinal measurements of aortic root diameters using high-resolution ultrasound imaging display significantly decreased aortic root diameters and lower pulse wave velocity in doxycycline-treated Marfan mice starting at 6 months as compared to their non-treated MFS counterparts. In addition, at the ultrastructural level, our data show that long-term doxycycline treatment corrects the irregularities of elastic fibers within the aortic wall of Marfan mice to the levels similar to those observed in control subjects. Our findings underscore the key role of matrix metalloproteinases during the progression of aortic aneurysm, and provide new insights into the potential therapeutic value of doxycycline in blocking MFS-associated aortic aneurysm.

Purpose of Review: Marfan syndrome (MFS) is the most common cause of aortic aneurysm in children and is associated with premature mortality. Whereas surgical therapy remains the primary treatment to prevent aortic complications, medical therapy may slow or prevent aortic growth. Pediatricians and pediatric cardiologists should become familiar with the diagnosis and management of MFS. This review focuses on the medical management for the most important life-threatening manifestation of MFS, thoracic aortic disease., Recent Findings: Several large-scale clinical trials and one meta-analysis have been reported comparing angiotensin receptors blockers with the standard therapy, beta blockers., Summary: From the assembled evidence described in this review, beta blockers and angiotensin receptors blockers show clinical equivalence and either class of agent may be an appropriate choice for the medical management of aortic growth in children with MFS.

Background/aims: We have reported that nitrosonifedipine (NO-NIF), a photodegradation product of nifedipine, has strong antioxidant and endothelial protective effects, and can suppress several cardiovascular diseases in animal models. The objective of the present study was to investigate the effects of NO-NIF on aortic aneurysm formation., Methods: The mice were infused with β-aminopropionitrile for 2 weeks and angiotensin II for 6 weeks to induce aortic aneurysm formation. The oxidative stress was measured by dihydroethidium staining and nitrotyrosine staining. The expressions of inflammation-related genes were assessed by quantitative real-time PCR and immunohistochemical staining. To clarify the mechanisms of how NO-NIF suppresses vascular cell adhesion molecule (VCAM)-1, endothelial cells were used in in vitro system., Results: NO-NIF suppressed pharmacologically induced the aortic aneurysm formation and aortic expansion without blood pressure changes. NO-NIF suppressed elastin degradation and matrix metalloproteinase-2 mRNA expression. NO-NIF suppressed the reactive oxygen species-cyclophilin A positive feedback loop. Upregulated mRNA expressions of inflammation-related genes and endothelial VCAM-1 were suppressed by NO-NIF co-treatment in aortae., Conclusion: NO-NIF has the potential to be a new, nifedipine-derived therapeutic drug for suppressing aortic aneurysm formation by directly improving aortic structure with its strong ability to reduce oxidative stress and inflammation., (© 2018 S. Karger AG, Basel.)

Background: Surgeon modification of commercially available aortic stent grafts represents a salvage option to treat complex aortic pathologies in high-risk patients., Technique: A 68-year-old male was referred to our hospital with a contained rupture of the visceral aorta. The patient was previously treated with an infrarenal tube graft 16 years earlier as well as with a Crawford procedure with island patch of the celiac trunk (TC) and the superior mesenteric artery (SMA) and bypasses to both renal arteries 6 years before admission. The computed tomography demonstrated a "blowout aneurysm" of the TC and SMA patch. The bypass to the left renal artery originated from the level of the TC. We therefore modified a commercially available t-branch (Cook ® Medical, Bloomington, IN) with surgeon-made fenestrations for both renal arteries. The procedure was successful, and the patient could be discharged to home on the seventh postoperative day., Conclusions: The use of surgeon-modified "off-the-shelf" t-branches broadens the possibilities of treating even anatomically very challenging aortic pathologies otherwise not suitable for the t-branch., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The aim of this study is to describe our institutional experience using iliac branch grafts (IBGs) in aortoiliac aneurysm repair., Methods: From October 2009 to April 2016, 41 consecutive patients (all men), mean age 71.7 years (range 55-87), underwent IBG implantation. Abdominal aortic aneurysm with common iliac artery involvement (n = 21) or bilateral common iliac artery aneurysms (n = 20) were indications. Computed tomography was used to evaluate patency and postoperative endoleaks within 1 month of implantation and after 1 year., Results: A total of 42 IBGs were deployed in 41 patients successfully. One hundred percent of grafts implanted were patent at 1 month and at annual follow-up. There was 1 mortality at 30 days, due to acute renal failure. Sixteen type II and 1 type Ib endoleaks were found, for which 3 reinterventions were performed and the remainder treated conservatively. Five patients had complications which required reintervention., Conclusions: IBG placement has excellent short-term outcomes and potential to limit buttock claudication in the treatment of abdominal aortic aneurysms involving the iliac arteries., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Rationale: Abdominal aortic aneurysms (AAAs) are mostly asymptomatic. If aortic aneurysms become symptomatic, complications include peripheral embolization, acute aortic occlusion, and aortic rupture. However, there are also unusual complications caused by aortic aneurysms., Patient Concerns: An 87-old male with dabigatran therapy presented with newly developed melena and acute renal failure. Radiological imaging revealed an AAA with thrombotic and calcified deposits which affected the renal arteries., Diagnoses: Gastrointestinal bleeding and hypercoagulation caused by renal failure which was triggered in turn due to an AAA., Interventions: Adapted antihypertensive therapy and initiation of simvastatin 40mg once daily as well as antiplatelet therapy with aspirin 50 mg once daily due to patient's refusal of any aneurysm intervention., Outcome: Neither bleeding event nor aneurysm rupture occurred with the adapted antihypertensive therapy, simvastatin and aspirin., Lessons: Nonruptured AAAs can cause rare, unusual, and even life-threatening complications depending on their size and anatomical position.

Objectives: Outcome in patients with acute coronary syndrome (ACS) is improved with dual antiplatelet therapy (DAPT). Patients with acute aortic dissection type A (AAD) often present with similar symptoms and may therefore be prescribed DAPT before diagnosis. The aim of this study was to evaluate the use of antiplatelet therapy (APT) prior to AAD surgery and patient outcome, including indications according to the European Society of Cardiology's (ESC) recent guidelines., Design: A retrospective, observational study., Setting: A tertiary University Hospital, Rigshospitalet, Heart Centre, Copenhagen, Denmark., Participants: The study included 171 patients operated for AAD during 2010 to 2014., Interventions: The independent relationship of preoperative APT was explored on 30-day mortality, intraoperative bleeding and perioperative transfusion requirements. Furthermore, the indications for APT were obtained., Measurements and Main Results: Patients receiving APT (n = 73) did not have an increased 30-day mortality (29% v 20%, p = 0.18). However, APT increased intraoperative bleeding by 45% (p<0.001) and increased perioperative transfusion of red blood cells by 71%, fresh frozen plasma by 52%, and platelets by 56% (p = 0.002). Among patients receiving APT preoperatively, 26 patients received acetylsalicylic acid (ASA) alone and 46 patients received DAPT. Bleeding was significantly more pronounced in patients receiving DAPT (5.6±4.1 L), compared to ASA alone (3.6±3.1 L) and no APT (3.3±4.8 L) (p<0.001). However, there was no significant difference in mortality between groups. DAPT, including ticagrelor, increased intraoperative bleeding by 62% compared to DAPT with clopidogrel (p = 0.004). Among patients receiving DAPT, only 30% of the patients fulfilled ESC criteria for ACS treatment., Conclusions: The use of APT was associated with increased intraoperative bleeding and transfusion requirement; however, it was not associated with a statistically significant increased mortality. Only a minority of patients fulfilled ESC criteria for ACS treatment with DAPT., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Surgical therapy for acute aortic dissection type A (AADA) in octogenarians carries high morbidity and mortality. The role of isolated medical treatment in this setting is controversial. The aim of this study is to determine whether risk of surgery for AADA outweighs risk of death from medical treatment only., Methods: From 2002 to 2015, 90 consecutive octogenarians (mean age, 83.5 ± 3 years) were treated for AADA at three institutions: 67 patients underwent surgery, 23 patients received medical treatment. Analysis of early and late outcome was performed., Results: Patients in the medical treatment group were significantly older than in the surgical group (84.9 ± 3.7 vs 83 ± 2.5 years, P  = 0.008) and in a more critical state. In patients undergoing surgical repair, perioperative mortality was 14.9% ( n  = 10). Rate of prolonged ventilation (63.2% vs 5.9%; P  < 0.001) and renal failure (35.1% vs 5.9%, P  = 0.029) was significantly higher in the surgical group. Thirty-day survival was impaired in the medical treatment group (34.8% vs 61.2% in the surgical group; P  = 0.032). Coronary artery disease (OR 3.95, 95% CI 1.16-13.49; P  = 0.029) and complicated dissections (OR 5.28, 95% CI 1.48-18.88; P  = 0.010)-composite variable of preoperative resuscitation, neurological injury and malperfusion-emerged as independent risk factors for 30-day mortality in the surgical group. There was no difference in long-term survival., Conclusions: Emergency surgery for AADA in octogenarians is associated with relatively high intraoperative mortality and may reasonably be avoided in patient with complicated presentation. Despite better immediate survival after surgery, long-term survival does not differ between medical and surgical patients, reflecting the extremely advanced point in life cycle octogenarians., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The aim of this study was to evaluate the value of fully integrated [18F]-FDG PET/MRI in the assessment of retroperitoneal fibrosis with regard to disease activity, extent and vascular involvement compared to clinical and laboratory parameters., Methods: Seventeen [18F]-FDG PET/MRI examinations were performed in fourteen patients. Qualitative (visual 4-point scale) and quantitative PET parameters (maximum standardised uptake value, SUVmax; target-background ratio, TBR) as well as RF thickness and volume were correlated to clinical and inflammatory parameters and compared between therapy-naïve patients and patients under immunosuppression. Evidence for associated large-vessel vasculitis was examined. Magnetic resonance angiography (MRA) was performed to detect aneurysms or stenoses., Results: Clinical parameters, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) only incompletely displayed inflammatory activity and did not correlate with PET/MRI parameters. In 29% (4/17) resp. 50% (8/16) of PET/MRI examinations active disease was detected although CRP resp. ESR were in the normal range. SUVmax, TBR and volume of the retroperitoneal mass differed significantly between therapy-naïve patients and patients under therapy (SUVmax p=0.004, TBR p=0.015, volume p=0.015), whereas thickness of the retroperitoneal mass did not (p=0.406). Large-vessel vasculitis was detected in 21% (3/14) and aortic aneurysms in 14% (2/14) of patients. Vasculitis occurred apart from the site of RF in two patients., Conclusions: Whole body hybrid [18F]-FDG-PET/MRI is superior to clinical and inflammatory parameters in disease activity assessment of RF. There may be substantial disease activity despite inflammatory parameters in the normal range. Associated large-vessel vasculitis and aneurysms may occur apart from the site of RF.

Intraluminal thrombus is a consistent feature of human abdominal aortic aneurysm (AAA). Coagulation factor Xa (FXa) catalyses FII to thrombin (FIIa). We examined the effect of FXa/FIIa inhibition on experimental aortic aneurysm in apolipoprotein E-deficient (ApoE -/- ) mice infused with angiotensin II (AngII). The concentration of FXa within the supra-renal aorta (SRA) correlated positively with SRA diameter. Parenteral administration of enoxaparin (FXa/IIa inhibitor) and fondaparinux (FXa inhibitor) over 14 days reduced to severity of aortic aneurysm and atherosclerosis in AngII-infused ApoE -/- mice. Enteral administration of the FIIa inhibitor dabigatran had no significant effect. Aortic protease-activated receptor (PAR)-2 expression increased in response to AngII infusion. Fondaparinux reduced SRA levels of FXa, FIIa, PAR-2, matrix metalloproteinase (MMP)2, Smad2/3 phosphorylation, and MOMA-2 positive cells in the mouse model. FXa stimulated Smad2/3 phosphorylation and MMP2 expression in aortic vascular smooth muscle cells (VSMC) in vitro. Expression of MMP2 in FXa-stimulated VSMC was downregulated in the presence of a PAR-2 but not a PAR-1 inhibitor. These findings suggest that FXa/FIIa inhibition limits aortic aneurysm and atherosclerosis severity due to down-regulation of vascular PAR-2-mediated Smad2/3 signalling and MMP2 expression. Inhibition of FXa/FIIa may be a potential therapy for limiting aortic aneurysm.

Patients with Marfan syndrome (MS) face a high risk of aortic dissection during pregnancy. A dilated aortic root (>40 to 45 mm) is considered a relative contraindication for pregnancy. We investigated the risk for aortic dissection and pregnancy outcome in patients with MS. Women with MS who attended our cardiology high-risk pregnancy clinic from 2006 to 2015 were followed clinically and with serial echocardiograms by a multidisciplinary team. Beta blockers were offered and titrated by blood pressure and heart rate. Patients with aortic root dilation ≥40 mm were considered high-risk patients with MS. A consistent increase in aortic root diameter of >1 mm during pregnancy was classified as dilation during pregnancy; 31 pregnancies in 19 patients with MS were followed. Four pregnancies were terminated early because of prenatal diagnosis of fetal MS and 4 additional babies born with MS. Eight pregnancies were in patients with a dilated aortic root (40 to 46 mm); 21 patients (68%) were treated with β blockers. There were 2 cases of postpartum aortic dissection (6.5%): 1 type A dissection in a woman with a dilated aortic root who declined β blockers (1 of 8, 12.5%) and 1 type B dissection. Increasing aortic root diameter (>1 mm) in pregnancy was significantly associated with later aortic dissection (2 of 6 vs 0 of 21, p = 0.04). No maternal deaths occurred. All high-risk women with MS gave birth by cesarean section, whereas in the non-high-risk group mode of delivery was by obstetric indication. Preterm delivery rate was 41% (11 of 27). One antenatal fetal death and no major neonatal morbidity or mortality were observed. In conclusion, pregnant patients with MS, especially those with a dilating aortic root, are at high risk of aortic dissection, even with tight control of blood pressure and heart rate., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aneurysms are local dilations of an artery that predispose the vessel to sudden rupture. They are often asymptomatic and undiagnosed, resulting in a high mortality rate. The predisposition to develop thoracic aortic aneurysms is often genetically inherited and associated with syndromes affecting connective tissue homeostasis. This review discusses how elucidation of the genetic causes of syndromic forms of thoracic aortic aneurysm has helped identify pathways that contribute to disease progression, including those activated by TGF-β, angiotensin II and Notch ligands. We also discuss how pharmacological manipulation of these signaling pathways has provided further insight into the mechanism of disease and identified compounds with therapeutic potential in these and related disorders.

Aims: Aortic aneurysm is a disastrous vascular disease with high morbidity and mortality. Matrix metalloproteinases (MMPs), especially MMP-9, is implicated in the development of aortic aneurysm, but the effective MMP inhibitors are far from development. To develop new candidate compound for aortic aneurysm therapy, we evaluated the effects of salvianolic acid C (SalC) against the formation of aortic aneurysm., Materials and Methods: Aortic aneurysm was induced by implantation of angiotension II (AngII) minipump in apolipoprotein E-deficient (ApoE -/- ) mice. MMPs activity was evaluated by enzyme kinetic analysis in vitro and in-gel gelatin zymography in vivo. The formation of aortic aneurysm was confirmed based on aortic maximum diameter. Hematoxylin and eosin stain was used to evaluate aortic structure, picrosirius red stain was for collagen deposition, and orcein stain was for elastin fragmentation. Macrophage infiltration was detected by CD68 immunohistochemistry., Key Findings: Firstly, SalC showed significant inhibition on the activity of MMP-2 and MMP-9. Aortic aneurysm was defined as >50% increase in maximum diameter of aorta, and the down-regulated tendency of 20mg/kg SalC against formation of aortic aneurysm was detected. Also, 22.2% rupture was detected in ApoE -/- mice, while no rupture of aortic aneurysm was found with 20mg/kg SalC treatment. Then, SalC was detected to maintain the integrity of aortic structure and protect elastin against fragmentation. Finally, SalC considerably inhibited infiltration of macrophage in the injury site of aorta., Significance: SalC significantly ameliorated the progression of aortic aneurysm in ApoE -/- mice, and held great potential for aortic aneurysm therapy., (Copyright © 2016. Published by Elsevier Inc.)

Type A acute aortic dissection is a life-threatening vascular emergency because of its high morbidity and mortality. Platelet is a pivotal ingredient involved in the development of acute aortic dissection. In this study, we aimed to investigate whether mean platelet volume (MPV)/platelet count ratio predicts in-hospital complications and long-term mortality in type A acute aortic dissection. In this single-center and prospective cohort study, 106 consecutive patients with Stanford type A acute aortic dissection admitted to the hospital within 12 h after onset were recruited. The best cut-off value of MPV/platelet count ratio predicting all-cause mortality was determined by the receiver operator characteristic analysis. Patients were divided into high (H-MPV/platelet count) and low (L-MPV/platelet count) groups based on the cut-off value of 7.49 (10 fl/10/l). Patients were followed up for 3.5 years. Of the 106 acute aortic dissection patients, 71 (67.0%) died during the study period, with a median follow-up duration of 570 days. Compared to the L-MPV/platelet count group, patients with H-MPV/platelet count had a higher risk of in-hospital complications including hypotension, hypoxemia, myocardial ischemia/infarction, conscious disturbance, pericardial tamponade, paraplegia, and poor survival (all P < 0.05). In multivariable Cox regression models adjusted for potential confounders, MPV/platelet count ratio was positively associated with the hazard of all-cause mortality, irrespective of interventions either with medication only or urgent surgery, and the hazard ratios were 2.81 (95% confidence interval 1.28-4.48) for the H-MPV/platelet count group when taking L-MPV/platelet count group as the reference (P = 0.005). The MPV/platelet count ratio was a strong independent predictor for in-hospital complications and long-term mortality in patients with type A acute aortic dissection.