Atherosclerotic Aortic Aneurysm Research Articles

Serum proteomic identification and validation of two novel atherosclerotic aortic aneurysm biomarkers, profilin 1 and complement factor D

BackgroundEffective diagnostic biomarkers for aortic aneurysm (AA) that are detectable in blood tests are required because early detection and rupture risk assessment of AA can provide insights into medical therapy and preventive treatments. However, known biomarkers for AA lack specificity and reliability for clinical diagnosis.MethodsWe performed proteome analysis of serum samples from patients with atherosclerotic thoracic AA (TAA) and healthy control (HC) subjects to identify diagnostic biomarkers for AA. Serum samples were separated into low-density lipoprotein, high-density lipoprotein, and protein fractions, and the major proteins were depleted. From the proteins identified in the three fractions, we narrowed down biomarker candidates to proteins uniformly altered in all fractions between patients with TAA and HC subjects and evaluated their capability to discriminate patients with TAA and those with abdominal AA (AAA) from HC subjects using receiver operating characteristic (ROC) analysis. For the clinical validation, serum concentrations of biomarker candidates were measured in patients with TAA and AAA registered in the biobank of the same institute, and their capability for the diagnosis was evaluated.ResultsProfilin 1 (PFN1) and complement factor D (CFD) showed the most contrasting profiles in all three fractions between patients with TAA and HC subjects and were selected as biomarker candidates. The PFN1 concentration decreased, whereas the CFD concentration increased in the sera of patients with TAA and AAA when compared with those of HC subjects. The ROC analysis showed that these proteins could discriminate patients with TAA and AAA from HC subjects. In the validation study, these candidates showed significant concentration differences between patients with TAA or AAA and controls. PFN1 and CFD showed sufficient area under the curve (AUC) in the ROC analysis, and their combination further increased the AUC. The serum concentrations of PFN1 and CFD also showed significant differences between patients with aortic dissection and controls in the validation study.ConclusionPFN1 and CFD are potential diagnostic biomarkers for TAA and AAA and measurable in blood samples; their diagnostic performance can be augmented by their combination. These biomarkers may facilitate the development of diagnostic systems to identify patients with AA.

Abstract 10987: Effect of False Lumen Status on Systemic Inflammatory Response Induced by Acute Aortic Dissection

Introduction: Acute aortic dissection (AAD) frequently induces a systemic inflammatory reaction. However, the influence of dissection morphology on immune response remains to be elucidated. Hypothesis: False lumen (FL) status influences peripheral blood cytokine expression in patients with AAD. Methods: Serum concentrations of 29 cytokines were measured on admission (within 48 hours of symptom onset) in 44 patients with AAD. None were suffering shock or aortic rupture and none had an autoimmune or hematologic disease. The 44 patients were divided into 2 groups based on FL patency: those with a thrombosed FL (Group T [n=21]: median age, 76 years) and those with a partially thrombosed or fully patent FL (Group P [n=23]: median age, 61 years). Stanford classes did not differ between these groups (Group T: type A, n=7; type B, n=14 vs. Group P: type A, n=14; type B, n=9) (p=0.068). Laboratory values, including cytokine concentrations, were compared between these groups and a control group (Group C—patients with a non-ruptured atherosclerotic thoracic aortic aneurysm—n=20]: median age, 75 years) by Mann-Whitney test, with multiple comparisons subjected to Bonferroni correction. Results: Leukocyte counts (x10e3/μL) were increased in both groups (Group T: 9.5 [7.7, 11.7]; Group P: 14.0 [10.4, 18.0] vs. Group C: 5.8 [5.0. 7.1]) (both p<0.001), but CRP concentrations (mg/dL) were not (0.51 [0.15, 3.3], p=0.077 and 0.38 [0.10, 2.7], p=0.165 vs. 0.2 [0.1, 0.21]). D-dimer concentrations (μg/mL) were increased in Group P (28.8 [8.6, 108], p<0.001) but not in Group T (2.9 [1.5, 5.3], p=0.87) (vs. Group C: 2.5 [1.4, 4.9]). Seventeen cytokines [IFNγ, IL-2, IL-4, IL-17α, TNFα, etc.] did not differ significantly between the 2 AAD groups; 12 did differ significantly. The differentially expressed cytokines fell into 3 hierarchical clusters: cluster A (increased expression in both groups [G-CSF, IL-6, IL-10, IL-15]), cluster B (increased expression only in Group P [GM-CSF, IL-1Ra, IL-1b, IL-8, IL-12p70, IP-10], and cluster C (increased expression only in Group T [IL-5, VEGF]). Conclusions: A robust inflammatory response occurs regardless of FL status, but the response is somewhat attenuated in patients with a thrombosed FL vs. those with a patent FL.

One-Stage Hybrid Total Aortic Arch and Descending Thoracic Aortic Repair is a Safe and Secure Procedure With Less Postoperative Complications for Extended Aortic Arch Aneurysms

Purpose Hybrid aortic arch repair (HAR) has been implemented for extended aortic arch and descending thoracic aortic disease since 2012 in our institution. This study aimed to estimate the early and mid-term efficacy and safety of HAR. Materials and Methods From 2007 to 2019, 56 patients underwent HAR for extended aortic arch disease, and 75 patients underwent total arch replacement (TAR) for arch-limited disease. HAR comprises 3 procedures: replacement of the aorta, reconstruction of all arch vessels, and thoracic endovascular aortic repair (TEVAR) from zone 0 to the descending aorta after cardiopulmonary bypass is off in 1 stage. The type II-1 HAR procedure, in which the ascending aorta and aortic arch distal to the brachiocephalic artery are replaced, was the most frequently selected procedure (40/56 patients). The outcomes of the type II-1 HAR procedure were compared with those of TAR using the Cox regression analysis. Results The median follow-up period was 36 months. In HAR, the operative mortality, in-hospital mortality, and postoperative permanent neurological deficits were not observed. The paraplegia rate was 1.8%. TEVAR-related complications occurred in 3 patients. Among the patients with non-ruptured atherosclerotic aortic arch aneurysm (31 type II-1 HAR patients and 36 TAR patients, the postoperative respiratory support time in those who underwent type II-1 HAR was quicker than in those who underwent TAR (p<0.01). The rate of 6 year freedom from all-cause death in type II-1 HAR (83.1%) was numerically higher than that in TAR (74.7%), and the rate of 6 year freedom from surgery-related complications in type II-1 HAR (90.3%) was numerically lower than that in TAR (96.9%) due to the occurrence of TEVAR-related complications, and the rate of 6 year freedom from reintervention to the descending thoracic aorta in type II-1 HAR (100%) seemed to be better than that in TAR (83.7%). However, Cox regression analysis did not reveal any statistical difference between the 2 procedures. Conclusions HAR, especially the type II-1 procedure, can treat extended aortic arch disease with acceptable survival outcomes. The development of TEVAR technology will further improve the outcomes of HAR in the future.

A simplified isolation technique for atherosclerotic aortic arch aneurysms surgery.

The isolation technique is a useful adjunct that prevents atherosclerotic embolism in the brain when the aneurysm is filled with a massive hematoma or ‘shaggy aorta’. But the technique is not widespread because of the difficulty in performing the cannulation. We modified this technique by simplifying the cannulation procedure using a puncture method with aortic root cannulas.

Patients with atherosclerotic peripheral arterial disease have a high risk of lung cancer: Systematic review and meta-analysis of literature.

Lung cancer and atherosclerosis share common risk factors. Literature data suggest that the prevalence of lung malignancy in patients with peripheral arterial disease (PAD) is higher than in the general population. Our goal was to determine, through a systematic literature review, the prevalence of lung cancer in patients with PAD. We consulted available publications in the Cochrane library, MEDLINE, PUBMED, EMBASE, and ClinicalTrials.gov. We included all articles, written in English or French, published between 1990 and 2020 reporting the prevalence of lung cancer in patients with PAD (atherosclerotic aortic aneurysm or peripheral occlusive diseases). Patients with coronary artery disease, cardiac valvulopathy or carotid stenosis were not included. We did not include case reports. We performed a critical analysis of each article. Data were collected from two independent readers. A fixed effect model meta-analysis allowed to estimate a summary prevalence rate. We identified 303 articles, and selected 19 articles according to selection criteria. A total of 16849 patients were included (mean age 68.3 years, 75.1% of males). Aortic aneurysms were found in 29% of patients and atherosclerotic occlusive disease in 66% of patients. Lung cancer was identified in 538 patients, representing a prevalence of 3%. Lung cancer is found in 3% of patients with atherosclerotic PAD. This prevalence is higher than that found in lung cancer screening programs performed in the general population of smokers and former smokers. These patients should be screened for lung cancer. Their selection may dramatically increase the benefit of lung cancer screening.

Upregulated Kynurenine Pathway Enzymes in Aortic Atherosclerotic Aneurysm: Macrophage Kynureninase Downregulates Inflammation.

Aims: Inflammation and hypertension contribute to the progression of atherosclerotic aneurysm in the aorta. Vascular cell metabolism is regarded to modulate atherogenesis, but the metabolic alterations that occur in atherosclerotic aneurysm remain unknown. The present study aimed to identify metabolic pathways and metabolites in aneurysmal walls and examine their roles in atherogenesis. Methods: Gene expression using microarray and metabolite levels in the early atherosclerotic lesions and aneurysmal walls obtained from 42 patients undergoing aortic surgery were investigated (early lesion n =11, aneurysm n =35) and capillary electrophoresis–time-of-flight mass spectrometry (early lesion n =14, aneurysm n =38). Using immunohistochemistry, the protein expression and localization of the identified factors were examined (early lesion n =11, non-aneurysmal advanced lesion n =8, aneurysm n =11). The roles of the factors in atherogenesis were analyzed in macrophages derived from human peripheral blood mononuclear cells. Results: Enrichment analysis using 35 significantly upregulated genes (log2 ratio, ＞3) revealed the alteration of the kynurenine pathway. Metabolite levels of tryptophan, kynurenine, and quinolinic acid and the kynurenine-to-tryptophan ratio were increased in the aneurysmal walls. Gene and protein expression of kynureninase and kynurenine 3-monooxygenase were upregulated and localized in macrophages in the aneurysmal walls. The silencing of kynureninase in the cultured macrophages enhanced the expression of interleukin-6 and indoleamine 2,3-dioxygenase 1. Conclusion: Our study suggests the upregulation of the kynurenine pathway in macrophages in aortic atherosclerotic aneurysm. Kynureninase may negatively regulate inflammation via the kynurenine pathway itself in macrophages.

Discovery of novel biomarkers for atherosclerotic aortic aneurysm through proteomics-based assessment of disease progression

Since aortic aneurysms (AAs) are mostly asymptomatic, but they have a high mortality rate upon rupture, their detection and progression evaluation are clinically important issues. To discover diagnostic biomarkers for AA, we performed proteome analysis of aortic media from patients with thoracic atherosclerotic AA (TAAA), comparing protein levels between the aneurysm and normal tissue areas. After hierarchical clustering analysis of the proteome analysis data, tissue samples were classified into three groups, regardless of morphological features. This classification was shown to reflect disease progression stage identified by pathological examination. This proteomics-based staging system enabled us to identify more significantly altered proteins than the morphological classification system. In subsequent data analysis, Niemann-Pick disease type C2 protein (NPC2) and insulin-like growth factor-binding protein 7 (IGFBP7) were selected as novel biomarker candidates for AA and were compared with the previously reported biomarker, thrombospondin 1 (THBS1). Blood concentrations of NPC2 and IGFBP7 were significantly increased, while THBS1 levels were decreased in TAAA and abdominal atherosclerotic AA patients. Receiver operating characteristic analysis of AA patients and healthy controls showed that NPC2 and IGFBP7 have higher specificity and sensitivity than THBS1. Thus, NPC2 and IGFBP7 are promising biomarkers for the detection and progression evaluation of AA.

Lipidomic signatures of aortic media from patients with atherosclerotic and nonatherosclerotic aneurysms

Aortic aneurysms are associated with fatal aortic rupture. Current therapeutic approaches are limited to implantation of aortic prostheses and stent-grafts; no effective drugs are available because the pathogenic mechanisms of aortic aneurysms remain unclear. Here, we aimed to elucidate the molecular mechanisms of the initiation and progression of aortic aneurysm by lipidomics. We performed lipidomics analyses of lipids in the aortic media of normal, border, and aneurysm areas from patients with thoracic atherosclerotic aortic aneurysm (N = 30), thoracic nonatherosclerotic aortic aneurysm (N = 19), and abdominal atherosclerotic aortic aneurysm (N = 11) and from controls (N = 8) using liquid chromatography and mass spectrometry. Significant alterations were observed in the lipid profiles of patients with atherosclerotic aortic aneurysms and to a lesser extent in those with nonatherosclerotic aneurysms. Increased triacylglycerols (TGs) and decreased ether-type phosphatidylethanolamines (ePEs) were observed throughout the normal, border, and aneurysm areas of thoracic and abdominal atherosclerotic aortic aneurysms. Prostaglandin D2 increased, but ePEs and TGs decreased in normal areas of thoracic atherosclerotic aortic aneurysms and thoracic nonatherosclerotic aortic aneurysms compared with the control tissues. These findings expand our knowledge of metabolic changes in aortic aneurysms and provide insights into the pathophysiology of aortic aneurysms.

Urgent Endovascular Treatment for Non-traumatic Descending Thoracic Aortic Rupture.

To evaluate the efficacy of endovascular repair of non-traumatic rupture of the descending thoracic aorta. From January 2011 to August 2017, 22 consecutive patients (16 men, mean age 73.7years, range 63-92years) with non-traumatic rupture of the descending thoracic aorta were treated endovascularly. Thirty-day mortality as well as procedure-related morbidity including stroke, renal, pulmonary and spinal complications were retrospectively assessed. Median follow-up was 29months (range 6-65months). Nine patients had type B dissections, and 13 had atherosclerotic aortic aneurysms. The technical success was 100%; 86.3% of patients (19/22) were treated percutaneously. Thirteen patients (59%) received a single endograft, 8 (36%) received 2 endografts, and 1 received 3 endografts. The endograft diameters ranged between 28 and 46mm. Two dissection patients received additional distal bare metal true lumen stents. Eleven patients required additional drainage of thoracic hematoma. Three primary percutaneous sites (15.7%) required surgical revision. No spinal cord ischemic or renal complications were observed. Stroke was observed in 2 patients (9%), both with full coverage of left subclavian artery origin. Four patients (18%) required tracheostomy with prolonged respiratory support (range 10-15days). The median intensive care unit stay was 5days (range 1-27days). The 30-day mortality was 18.1% (4/22). Endoluminal repair of non-traumatic rupture of the descending thoracic aorta can be performed percutaneously. It showed a 30-day mortality of 18.1%, and no spinal cord injury or renal complications were observed in surviving patients at follow-up. Level 4, case series.

A case of anterior spinal cord syndrome in a patient with unruptured thoracic aortic aneurysm with a mural thrombus

BackgroundSpinal cord infarction is an uncommon condition. Anterior cord syndrome present with paraparesis or quadriparesis with sparing of vibration and proprioceptive senses. The common causes of anterior cord syndrome are aortic dissection and aortic surgical interventions. Spontaneous unruptured nondissected aortic aneurysms with intramural thrombus can rarely cause anterior cord infarctions.Case presentationWe report a case of anterior spinal cord syndrome due to aneurysm of the thoracic aorta with a mural thrombus. A 64 year old male presented with sudden onset paraparesis with a sensory level at T1 with preserved sense of proprioception and vibration. The MRI panspine revealed increased T2 intensity in the anterior portion of the spinal cord from C5 to T10 level with characteristic ‘owl eye’ appearance on axial imaging. The CT aortogram detected aneurysmal dilatation of the ascending aortic, arch and descending thoracic aorta with significant intimal irregularities, calcified atherosclerotic plaques and a small mural thrombus.ConclusionThe possible mechanisms postulated are occlusion of ostia of radicular arteries by the atherosclerotic plaques and mural thrombus or thromboembolism to the anterior spinal artery. Nondissected atherosclerotic aortic aneurysms should be considered in patients presenting with spinal cord infarctions especially in the presence of vascular risk factors and smoking.

Mathematical modeling of pulse wave propagation along human aorta

Background: Physical characteristics of pulse waves, which are generated by the heart contractions and propagated along the arteries, are used in medicine for diagnostics of the blood circulation system and blood supply to the organs and tissues. At the sites with significant wave reflections the high local pressure oscillations appear that may lead to damage of the endothelium, development of atherosclerotic plaques and aortic aneurysm. Therefore, elaboration of a detailed biophysical model of the individual aorta based on tomography and determination of the dangerous sites with high wave reflections are important for medical diagnostics. Objectives: The aim of the work is to study the regularities of the pulse wave propagation and reflection along the aorta and to propose new methods for early diagnosis of disorders in the blood circulation system. Materials and methods: The measurement data on diameters and lengths of segments of aorta and its branches conducted on 5 corpses have been used. Calculations of the wave conduction and reflection coefficients are based on the linear theory of pulse waves developed by J. Lighthill. Results: It is shown that from the biophysical point of view, the aorta is an optimal waveguide, which provides almost zero local reflections of the pulse waves. Most of the branches possess negative reflection, which accelerates the blood flow and decreases the load on the heart due to the suction effect. The calculated values of the branching coefficients and pulse waves speeds correspond to the data of the previous experimental measurements. It is shown that most of the branches have an optimal Murray coefficient close to one. It implies, aorta also provides the optimal volumetric blood flow over the period of cardiac contraction with minimal energy expenses. Conclusions: Human aorta and its branches possess optimal biophysical properties, which ensure the blood flow with minimal energy consumption. Aorta as an optimal waveguide provides pulse wave propagation with almost without reflection. The proposed method of estimation of the biophysical properties of aorta as a waveguide can be useful for medical diagnostics, allowing early identification of the regions which are dangerous in terms of the progressive development of vascular pathologies in the individual geometry of the patient's vasculature.

Abstract 19: Role of Adenosine-to-Inosine RNA Editing of Alu Elements in Human Vascular Inflammatory Diseases

Background: Adenosine to inosine (A-to-I) RNA editing is catalysed by ADARs (adenosine deaminases acting on RNA) and is an important posttranscriptional regulator of RNA metabolism. Although RNA editing is essential for life, its role in cardiovascular disease is unknown. Methods and Results: RNA-sequencing (RNA-seq) of human endothelial cells revealed that ADAR1 is the main RNA editor in HUVECs. The vast majority of editing events are detected in Alu regions due to their ability to form double-stranded structures, a prerequisite for RNA editing. A-to-I RNA editing of the primate-specific Alu elements is observed in 25% of poly(A)+ transcripts and in 44% of ribosomal RNA-depleted transcripts. Cathepsin S (CTSS), an extracellular matrix degrading enzyme, has 3 Alu elements in its 3’-untranslated region and is among the most extensively edited mRNAs. Interestingly, ADAR1 silencing downregulates CTSS mRNA expression, whereas ADAR1 overexpression results in an increase of both CTSS RNA editing rate and CTSS mRNA expression. Mechanistically, RNA immunoprecipitation (RIP), luciferase reporter and iCLIP assays showed that A-to-I RNA editing of the Alu elements in the 3’UTR of CTSS mRNA regulates the recruitment of the stabilizing RNA-binding protein HuR to CTSS 3’UTR and, thus, controls CTSS mRNA stability and expression. CTSS Alu RNA editing is increased under hypoxic or pro-inflammatory conditions in vitro , as well as in patients with coronary or carotid atherosclerotic vascular disease. Further, the extent of CTSS Alu RNA editing rate correlated with various markers of subclinical atherosclerosis including intima-media thickness and number of atherosclerotic plaques. Importantly, ADAR1 and the extent of CTSS RNA editing correlated with CTSS expression levels in patients’ samples from 6 non-overlapping cohorts of patients with inflammatory vascular diseases (total n=366), including peripheral blood mononuclear cells, carotid atherosclerotic plaques and thoracic aortic aneurysms. Conclusion: This study shows for the first time that Alu A-to-I RNA editing is a critical modulator of inflammatory gene expression in all stages of atherosclerotic vascular disease development.

Abstract 18889: Circulating microRNA Implicated in the TGF-β Signalling Pathway are Altered in Marfan Syndrome

Thoracic aortic aneurysms in Marfan Syndrome (MFS) caused by mutations in FBN1 are associated with altered TGF-β signaling. Regulation of gene expression can occur at the level of microRNA, which can modify signaling pathways. We hypothesized that there would be altered microRNA expression in MFS that may alter the expression of signaling proteins. Total RNA was isolated from whole blood collected in PAXgene® tubes (PreAnalytiX), from 13 MFS patients with aortic dilatation (6F, 7M; Ao Diameter 44.4±6.0mm; Age 39±12yrs) and 10 normal controls (5F, 5M; Ao Diameter 32.3±5mm; Age 34±10yrs). The RNA was reverse transcribed with Human Pool A &amp; B primers and qPCR was performed on the subsequent cDNA using TaqMan® OpenArray® Human miRNA Panels (2454 targets) (ThermoFisher). microRNA expression was considered to be significantly altered if there was &gt;2 fold change (p&lt;0.05) compared to controls. microRNA that were identified as significantly altered were then validated with qPCR using targeted primers on an additional 33 MFS patients (15F, 21M; Ao Diameter 44.2±5.0mm; Age 37±13yrs). In MFS patients, the OpenArray® identified 30 microRNA were significantly altered (22 up regulated, 8 down regulated). Of these, 12 were confirmed to be altered using targeted qPCR (Graph 1). Three of these have previously been identified as modifiers of the TGF-β signaling pathway (miR 17, miR 93, miR 93*). Three were from the let-7 family (let-7e, let-7f, let-7g), which are involved in terminal cell differentiation and have been implicated in several cardiovascular disease processes. Another three have been shown to be dysregulated in various cardiovascular disease states including atherosclerotic thoracic aortic aneurysm and left ventricular hypertrophy (miR 208, miR 486, miR 378). This study provides novel evidence for adaptive responses at the post-transcriptional level of gene expression that may modulate aneurysm development in Marfan syndrome.

An elevated IgG4 response in chronic infectious aortitis is associated with aortic atherosclerosis

Recently, it was shown that infectious bacterial aortitis can stimulate an elevated IgG4+ plasma cell response in the vessel wall, which could mimic IgG4 aortitis/periaortitis. However, the factors that are associated with an elevated IgG4+ plasma cell response in infectious aortitis are unclear. To ascertain these factors, 17 cases of infectious aortitis and 6 cases of non-infectious severe abdominal aortic atherosclerosis were assessed for the magnitude of IgG4+ plasma cell response. The degree of IgG4+ plasma cell infiltration was determined by immunohistochemistry. Infectious cases were subcharacterized as chronic (>3 weeks duration) or acute (<3 weeks duration) based on the duration of symptoms, and as involving either the ascending aorta or the distal aorta, ie, the descending thoracic and/or abdominal aorta. There was a 5–16-fold greater degree of IgG4+ plasma cell infiltration in the chronic distal infectious aortitis group compared with the other three infectious aortitis groups (P≤0.0007), and compared with non-infectious severe abdominal aortic atherosclerosis (P<0.0008). This resulted in a greater IgG4/IgG ratio in the chronic distal infectious aortitis group compared with the acute ascending and acute distal infectious aortitis groups (P<0.03). The degree of IgG4+ plasma cell infiltration in chronic distal infectious aortitis overlaps with that seen in the aortitis and periaortitis of IgG4-related disease. In the chronic infectious aortitis cases, the degree of IgG4+ plasma cell infiltration was more intense in patients with moderate to severe aortic atherosclerosis compared with those patients with less aortic atherosclerosis (P=0.007). These findings indicate that an elevated IgG4+ plasma cell response occurs in the descending thoracic and abdominal aorta in the setting of chronic bacterial infectious aortitis and pre-existing atherosclerosis. This inflammatory response to chronic infection in atherosclerosis-laden aortas may have implications for the development of IgG4-rich inflammatory atherosclerotic aortic aneurysms.

Early detection of vulnerable atherosclerotic plaque for risk reduction of acute aortic rupture and thromboemboli and atheroemboli using non-obstructive angioscopy.

The mortality rate due to rupture of aortic dissection and aortic aneurysm is approximately 90%. Acute aortic rupture can be fatal prior to hospitalization and has proven difficult to diagnose correctly or predict. The in-hospital mortality rate of ruptured aortic aneurysm ranges from 53 to 66%. Emergency surgical and endovascular treatments are the only options for ruptured aortic dissection and aortic aneurysm. No method of systematic early detection or inspection of vessel injury is available at the prevention stage. Regardless of the improvement in many imaging modalities, aortic diameter has remained a major criterion for recommending surgery in diagnosed patients. Previous reports have suggested a relationship between vulnerable plaque and atherosclerotic aortic aneurysm. Non-obstructive angioscopy is a new method for evaluating intimal injury over the whole aorta. It has been used to identify many advanced atherosclerotic plaques that were missed on traditional imaging modalities before aneurysm formation. Non-obstructive angioscopy has shown that atherosclerosis of the aorta begins before that of the coronary artery, which had been noted on autopsy "in vivo". Strong or repetitive aortic injuries might cause sudden aortic disruption. Aortic atheroma is also a risk factor of stroke and perivascular embolism. Detecting aortic vulnerable atherosclerotic plaque on non-obstructive angioscopy may not only clarify the pathogenesis of acute aortic rupture and "aortogenic" thromboemboli and atheroemboli but also play a role in the pre-emptive medicine.

Involvement of TLR2 and TLR4, &amp;lt;i&amp;gt;Chlamydophila pneumoniae&amp;lt;/i&amp;gt; and &amp;lt;i&amp;gt;Mycoplasma pneumoniae&amp;lt;/i&amp;gt; in adventitial inflammation of aortic atherosclerotic aneurysm

Aortic atherosclerotic aneurysm (AAA) is associated with adventitial inflammation where infection is suggested to have a role. Co-infection with Chlamydophila pneumoniae (Cp) and Mycoplasma pneumoniae (Mp) was linked with coronary plaque rupture, in association with vessel dilatation and adventitial inflammation. Pathogens are recognized by Toll-like receptors (TLRs) development of the inflammatory process. Objective: Here, we studied whether co-infection by Cp and Mp was involved in the increased inflammation present in AAA and if it could be associated with deficient expression of TLRs. We compared human samples of AAA with non-dilated human aortic atherosclerotic lesions, regarding the amount of Cp and Mp antigens, and expression of TLR2 and TLR4. Methods: Two groups of aorta fragments were analyzed: G1 (n = 13) moderate atherosclerosis and G2 (n = 14) AAA samples, through immunohisto-chemistry and in situ hybridization methods. Results: Mp and Cp antigens in intima/medial layer were greater in G2 than G1, with no difference in adventitia. TLR2 and TLR4 were higher in G2 than G1 adventitia fat. There was a correlation between Mp versus TLR2 and of TLR4 in intima/medial layer and in adventitia of G1, but there was a lack of correlation in G2. In Cp adventitia, the correlation in G1 was high with TLR2 but not with TLR4, and in G2 the correlation was positive for both TLRs. Conclusion: This study favors the concept that symbiotic co-infection by Cp and Mp participates in the pathogenesis of AAA. It also emphasizes that adventitial fat is the initial site for colonization of these bacteria that probably reach the tissue through vasa vasorum. An exacerbated immune reaction is not efficient to control the infection that reaches and proliferates in high levels at the medial and intimal layer, contributing to the development of vessel dilatation.

Correlation of Bacterial Coinfection Versus Matrix Metalloproteinase 9 and Tissue Inhibitor of Metalloproteinase 1 Expression in Aortic Aneurysm and Atherosclerosis

We searched for any relationship between Chlamydophila pneumoniae, Mycoplasma pneumoniae, matrix metalloproteinase 9 (MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) in aneurysmatic atherosclerotic lesions, and whether this relationship differed from that in atherosclerotic nonaneurysmatic lesions. Twenty-eight tissue samples paired by age and sex were grouped as follows: group 1 included 14 nonaneurysmal atherosclerotic fragments obtained from abdominal aortas collected from necropsies; group 2 included 14 aneurysmatic atherosclerotic aortic fragments obtained from patients during corrective surgery. Immunohistochemistry reactions were evaluated for C pneumoniae, M pneumoniae, MMP-9, and TIMP-1 antigens. Both groups were compared using the Mann-Whitney test, and the correlations among variables were obtained using the Spearman correlation test. P ≤ 0.05 was considered statistically significant. C pneumoniae and M pneumoniae antigens were detected in 100% of cases. A higher amount of C pneumoniae (P = 0.005), M pneumoniae (P = 0.002), and MMP-9 (P = 0.021) was found in adventitia of group 2 with aneurysm. A positive correlation was found in the aneurysm group, as follows: intima C pneumoniae versus adventitia thickness (r = 0.70; P = 0.01), media C pneumoniae versus adventitia C pneumoniae (r = 0.75; P = 0.002), intima C pneumoniae versus media C pneumoniae (r = 0.8; P = 0.00), and adventitia C pneumoniae versus intima M pneumoniae (r = 0.54; P = 0.05); negative correlations were as follows: adventitia thickness and adventitia M pneumoniae (r = -0.65; P = 0.01), media MMP-9 and media thickness (r = -0.55; P = 0.04), TIMP-1 media versus adventitia C pneumoniae (r = -0.86; P = 0.00), and TIMP-1 media versus M pneumoniae intima (r = -0.67; P = 0.03). Nonaneurysmal atherosclerotic group 1 results are as follows: adventitia C pneumoniae versus TIMP-1 media (r = 0.75; P = 0.01) and media C pneumoniae and adventitia C pneumoniae (r = 0.59; P = 0.03). The present work favors a role for coinfection of both M pneumoniae and C pneumoniae in the development of aortic atherosclerotic aneurysm, with increased adventitial inflammation, inhibition of TIMP-1 activity, and increased collagen degradation.

Predictors of early and late outcome after total arch replacement for atherosclerotic aortic arch aneurysm

This study aimed to identify predictors of early and late outcome after total arch replacement (TAR) for atherosclerotic aortic arch aneurysm. TAR with separate arch vessel grafting and selective cerebral perfusion was performed in 130 patients. The median age at operation was 72.9 ± 6.1 years (57-86 years). Emergency operation was performed in 9 patients (6.9 %) and the frozen elephant trunk technique was used in 51 patients (39.2 %). The in-hospital mortality rate was 3.8 %. Chronic renal failure (CRF) was identified as an independent predictor of in-hospital mortality (p = 0.0001). Permanent neurological dysfunction occurred in nine patients (6.9 %). Clot or atheroma in the aneurysm (p = 0.01) and the duration of selective cerebral perfusion (p = 0.011) were identified as independent predictors of permanent neurological dysfunction. Long-term survival rates were 82.0 % at 3 years, 70.0 % at 5 years, and 52.4 % at 8 years postoperatively. CRF (p = 0.0190), age (p = 0.0147), and permanent neurological dysfunction (p = 0.0048) were identified as independent predictors of long-term mortality. Prevention of permanent neurological dysfunction is crucial for long-term survival after TAR. Older patients with renal dysfunction may have reduced long-term survival after TAR.

Shaggy and calcified aorta: surgical implications

Atheroembolism is an emerging problem in cardiovascular surgery, especially in elderly patients. Severe atherosclerosis of the thoracic aorta usually reflects systemic atherosclerosis. Aggressive preoperative and intraoperative evaluation of the aorta using enhanced CT, transesophageal echocardiography and epiaortic ultrasound is important in elderly patients as well as those with systemic atherosclerosis. To prevent atheroembolism, it is important to select an adequate arterial perfusion site and to avoid touching the diseased aorta until circulatory arrest. In atherosclerotic aortic arch aneurysm, central cannulation under ultrasound guidance and directing the dispersive cannula toward the aortic root is a simple and effective perfusion strategy. Axillary perfusion is useful as an alternative to central cannulation in atherosclerotic aortic disease, but special care is necessary to avoid complications when the patient has a small axillary artery or flail atheroma around the arch vessels. In femoral artery perfusion, retrograde perfusion may induce paradoxical cerebral embolism, but the incidence of stroke is comparable with axillary perfusion when there is adequate preoperative screening using transesophageal echography. Circulatory arrest with/without cerebral perfusion is another important strategy when the aorta has severe atherosclerosis. Recent literature has shown that mild hypothermia may be safe for anterior cerebral perfusion during circulatory arrest, but optimal flow rates and time limitations are unknown. A simple calcified aorta called "porcelain aorta" may be managed by circulatory arrest, local debridement and the clamp method. Several surgical options are proposed for this clinical entity but their use will diminish in the future because of transcatheter valve replacement.

Fatal aortobronchial fistula

Aortobronchial fistula is a rare condition characterized by the development of a communication between the aorta and a branch of the bronchial tree that results from processes that arise within the aorta, in the tissues of the mediastinum, or in the adjacent thoracic organs. Three cases are reported to demonstrate characteristic features. Case 1: An 82-year-old woman was found collapsed with blood clot in her mouth. At autopsy an atherosclerotic thoracic aortic aneurysm was found which had eroded into the underlying left main bronchus with filling of the larynx, trachea and main bronchi with fluid blood. There was no evidence of dissection. Case 2: A 30-year-old woman collapsed and died. At autopsy, coarctation of the thoracic aorta was found with a saccular aneurysm distal to this which was joined to the left main bronchus by a mass of necrotic tissue. The bronchus contained a cast of blood; blood was also present within the trachea and within the distal airways of the left lung. Case 3: A six-year-old girl collapsed with massive airway haemorrhage following bronchoscopy. At autopsy coarctation of the thoracic aorta was identified with a saccular aneurysm distal to this. A transverse tear of the thinned aneurysm wall communicated with a mass of necrotic friable tissue that extended through the wall of the left main bronchus. Distal airways were filled with fluid blood. All three deaths were due to haemorrhage from aortobronchial fistulas. The pathogenesis of aortobronchial fistulas involves a variety of mechanical, infective and neoplastic processes. Many cases will not be diagnosed until autopsy examination is performed.