Development Of Aneurysms Research Articles

Abstract TMP16: Mechanoreceptor Dysregulation Found In Human Intracerebral Aneurysms

Introduction: About 500,000 people worldwide die annually from ruptured intracranial aneurysms (IA). The pathophysiology of aneurysm formation is largely unknown. Piezo1 mechanoreceptors are expressed in endothelial and smooth muscle cells of developing blood vessels. In addition to hemodynamic forces, Piezo1 has been shown to play an inflammatory role, as stiffness-sensing macrophages lacking Piezo1 exhibit reduced inflammation and enhanced wound healing responses. Malfunction of Piezo1 mechanoreceptors has been implicated in abdominal aortic aneurysm (AAA) development. With the increasing evidence of relationship between AAA and IAs, it is important to study Piezo1 dysregulation as a potential cause of IA development and/or rupture. Methods: During craniotomy for aneurysm clipping of ruptured and unruptured IAs, we excised and collected the aneurysm dome in four patients. Immunohistochemistry (IHC) was performed for Piezo1 and with CD31 to co-localize Piezo1 in the endothelial cells, and a-SMA to co-localize in smooth muscle cells on all aneurysm domes. Additional specimen was saved for genomic analyses. Results: Piezo1 mechanoreceptor overexpression was found in the smooth muscle layer of IAs, but not in superficial temporal artery (STA) controls, in all four human cerebral aneurysm domes. Additionally, there was significant dysregulation of Piezo1 mechanoreceptors in the IA compared with the regular appearance seen in the control human STA (Figure 1). Overexpression was not seen in human arteriovenous malformation specimens. Conclusions: Our data is the first demonstration of overexpression of Piezo1 mechanoreceptors in a disorganized manner in the walls of human IAs, which may represent a therapeutic target. We hypothesize that vascular shear stress leads to Piezo1-mediated disorganization in arterial smooth muscle cells and pro-inflammatory activation, which may lead to IA development and rupture.

Prognostic nutritional index value in the prognosis of Kawasaki disease with coronary artery lesions.

The prognostic nutritional index (PNI) is a purported predictor of intravenous immunoglobulin (IVIG) resistance and coronary artery aneurysm (CAA) development in patients with Kawasaki disease (KD). However, limited data exist on CAA regression. This study aimed to confirm whether the PNI is a predictor for CAA persistency in patients with KD. This retrospective study grouped 341 patients with KD based on the coronary artery status and time of aneurysm persistence. The clinical and laboratory parameters were compared, and multivariate logistic regression analysis was performed to identify the independent risk factors for persistent CAA. The receiver operating characteristic (ROC) curve was further used to assess the predictive values of the PNI in persistent CAA. Among the study patients, 80 (23.5%) presented with CAA, including CAA persisting for 2 years in 17 patients (5.0%). Patients with CAA were more frequently treated with corticosteroids (p < 0.016). No statistically significant differences were found in the nutritional status and PNI among patients with or without coronary artery lesions, regardless of injury severity. Patients in the persistent CAA group presented with higher rates of overnutrition and showed lower PNI values and a higher incidence of thrombosis than those in the normal group (p < 0.05). The PNI and the maximum Z-score at 1 month of onset were significantly associated with CAA persisting for 2 years and may be used as predictors of persistent CAA. The area under the ROC curve was 0.708 (95% confidence interval, 0.569-0.847), and a 40.2 PNI cutoff yielded a sensitivity and specificity of 41 and 92%, respectively, for predicting CAA persisting for 2 years. Kaplan-Meier survival analysis revealed that the estimated median time of aneurysm persistence was significantly higher in patients with PNI values of ≤40 than in those with PNI values of >40 (hazard ratio, 2.958; 95% confidence interval, 1.601-5.464; p = 0.007). After sampling-time stratification, the PNI differed significantly between patients with and without persistent CAA when sampled on the second (p = 0.040), third (p = 0.028), and fourth days (p = 0.041) following disease onset. A lower PNI value is an independent risk factor for CAA persisting for 2 years in patients with KD, besides the maximum Z-score at 1 month after onset. Furthermore, the PNI obtained within 4 days from fever onset may possess greater predictive power for patients with persistent CAA.

Abstract 122: The P2x4 Inhibitor, Paroxetine Dramatically Prevents Not Only Growth Of Unruptured Cerebral Aneurysms But Also Recanalization After Aneurysm Coil Embolization; A Retrospective Clinical Study, Drug For Aneurysm Study

Introduction: We have suggested that inhibition of P2X4 purinoceptor, which is involved in the endothelial flow sensing mechanism, prevents cerebral aneurysm development and growth in an animal model. Therefore, we retrospectively investigated whether a P2X4 inhibitor, paroxetine used as an antidepressant, has an inhibitory effect on the growth of unruptured cerebral aneurysms and the rate of recanalization after coil embolization. Methods: Among the cases registered in the J-ASPECT Study, the Japanese stroke inpatient reimbursement database, from 2010 to 2019, we searched for cases who were taking paroxetine and with registered unruptured cerebral aneurysm or had undergone cerebral aneurysm coil embolization. We then invited medical centers with these cases to participate in the study and enrolled cases that met the selection criteria by referring to the imaging data and patient background of the cases. The inhibitory effect in the paroxetine-treated group was compared with that of the control group in a multivariate analysis after adjustment for age, gender, and known risk factors. Results: There were 708 cases at 226 facilities nationwide that were potentially matched in the criteria. Seventy-four facilities participated, of which 74 cases at 45 facilities met the selection criteria. A total of 700 control cases were enrolled from 14 core participating centers. The rate of growth incidence of aneurysms was 0.0318 for paroxetine-treated cases (n=36) and 0.0960 for control cases (397). The significant factors (regression coefficients) were paroxetine (-2.26), specific sites of occurrence (-1.28), shape irregularity (1.63), age (0.11), female (1.54), hypertension (-0.55), statin (0.87), and family history of stroke (0.71). The significant factors (odds ratios) in recanalization after 1 year of coil embolization were paroxetine (0.21), complete embolization (0.26), ruptured aneurysm (3.95), and size (1.14). Conclusions: This retrospective study suggests that P2X4 inhibitors including paroxetine may be clinically applicable as agents to inhibit the growth of unruptured cerebral aneurysms and recanalization after 1 year of aneurysm coil embolization. The use of reimbursement information may be useful when collecting very rare cases.

IMAGING OF THE ANTERIOR COMMUNICATING ARTERY: NORMAL AND ABNORMAL FINDINGS RELATED TO ANEURYSM

The anterior communicating artery (AComA) is a critical component of the Circle of Willis, serving as a vital conduit that connects the bilateral anterior cerebral arteries. This study aims to provide a comprehensive overview of the imaging characteristics of the AComA, encompassing both normal variations and abnormal findings associated with aneurysm development. Utilizing advanced imaging techniques, a thorough analysis of the AComA complex was conducted in a cohort of subjects. Normal anatomical variants were meticulously documented, highlighting variations in length, diameter, and branching patterns. Abnormal findings indicative of potential aneurysm markers was carefully assessed, encompassing variations in morphology, hemodynamic flow patterns, and wall integrity. Special attention was given to elucidate the factors contributing to aneurysm initiation within the AComA complex. The clinical significance of distinguishing between normal anatomical variations and potential pathological findings was underscored, emphasizing the critical importance of early detection and intervention to mitigate the risks associated with aneurysm rupture. The findings of this study contribute valuable insights to the field of neurovascular diagnostics and therapeutic strategies. By enhancing our understanding of the AComA and its role in aneurysm development, this research aims to empower clinicians with the knowledge needed for informed decision-making and proactive management. Ultimately, the comprehensive examination of AComA imaging, encompassing both normal and abnormal variants, holds the potential to drive advancements in cerebrovascular care and improve patient outcomes.

Cardiovascular Involvement in Tuberculosis: From Pathophysiology to Diagnosis and Complications-A Narrative Review.

Although primarily a lung disease, extra-pulmonary tuberculosis (TB) can affect any organ or system. Of these, cardiovascular complications associated with disease or drug toxicity significantly worsen the prognosis. Approximately 60% of patients with TB have a cardiovascular disease, the most common associated pathological entities being pericarditis, myocarditis, and coronary artery disease. We searched the electronic databases PubMed, MEDLINE, and EMBASE for studies that evaluated the impact of TB on the cardiovascular system, from pathophysiological mechanisms to clinical and paraclinical diagnosis of cardiovascular involvement as well as the management of cardiotoxicity associated with antituberculosis medication. The occurrence of pericarditis in all its forms and the possibility of developing constrictive pericarditis, the association of concomitant myocarditis with severe systolic dysfunction and complication with acute heart failure phenomena, and the long-term development of aortic aneurysms with risk of complications, as well as drug-induced toxicity, pose complex additional problems in the management of patients with TB. In the era of multidisciplinarity and polymedication, evidence-based medicine provides various tools that facilitate an integrative management that allows early diagnosis and treatment of cardiac pathologies associated with TB.

Use of Secondary Iliac Branch Devices after Previous Endovascular Abdominal and Thoraco-Abdominal Aortic Aneurysm Repair

To assess the safety and effectiveness of iliac branch devices (IBDs), as secondary procedure, for the treatment of type Ib endoleak or evolution of iliac artery disease after prior endovascular aortic repair (EVAR) for thoraco-abdominal (TAAAs) or abdominal aortic aneurysms (AAAs). A multicentre observational study of three European centres. The study included 75 patients (age 71 ± 9 years, 96% men) with previous EVAR (n= 64, 85%) or fenestrated or branched (FB) EVAR (n= 11, 15%). Overall, 88 IBDs were implanted to treat aneurysmal iliac artery evolution in 40 (53%) and type Ib endoleak in 35 (47%) cases, respectively. Thirteen (17%) patients received bilateral IBDs. Internal iliac artery (IIA) catheterisation was done through a transaxillary access (n= 82, 93%) or up and over (n= 6, 7%) technique. The primary endpoint was technical success. Secondary endpoints were 30 day major adverse event, early and long term freedom from re-intervention and target vessel instability. All procedures were technically successful (100%). During hospitalisation, there were four (5%) major adverse events and three (4%) early re-interventions, but no death, stroke, or damage to previous endografts. The median follow up was 47 (interquartile range 42) months, and the five year survival rate was 78 ± 6% with no aortic related death. Cox's regression analysis showed pre-operative renal function impairment (hazard ratio [HR] 3.4; 95% confidence interval [CI] 1.1 - 10.1; p= .033), and primary TAAA repair (HR 6.1; 95% CI 1.6-22.3; p= .006) as independent factors for long term mortality. Freedom from re-interventions was 85 ± 4% at five years with 11 (12%) cases (five endoleaks, four IBD thromboses, two stenoses). IIA instability was reported in three (3%) limbs and freedom from IIA instability was 95 ± 3% after 60 months. Secondary IBD after EVAR is a safe and effective procedure with high technical success and low complication rates. The technique of choice to revascularise the IIA seems not to affect early and follow up results. Long term durability of IBD repair is acceptable with low rates of IIA re-intervention.

ADAR1 Non-Editing Function in Macrophage Activation and Abdominal Aortic Aneurysm.

Macrophage activation plays a critical role in abdominal aortic aneurysm (AAA) development. However, molecular mechanisms controlling macrophage activation and vascular inflammation in AAA remain largely unknown. The objective of the study was to identify novel mechanisms underlying adenosine deaminase acting on RNA (ADAR1) function in macrophage activation and AAA formation. Aortic transplantation was conducted to determine the importance of nonvascular ADAR1 in AAA development/dissection. Ang II (Angiotensin II) infusion of ApoE-/- mouse model combined with macrophage-specific knockout of ADAR1 was used to study ADAR1 macrophage-specific role in AAA formation/dissection. The relevance of macrophage ADAR1 to human AAA was examined using human aneurysm specimens. Moreover, a novel humanized AAA model was established to test the role of human macrophages in aneurysm formation in human arteries. Allograft transplantation of wild-type abdominal aortas to ADAR1+/- recipient mice significantly attenuated AAA formation, suggesting that nonvascular ADAR1 is essential for AAA development. ADAR1 deficiency in hematopoietic cells decreased the prevalence and severity of AAA while inhibited macrophage infiltration and aorta wall inflammation. ADAR1 deletion blocked the classic macrophage activation, diminished NF-κB (nuclear factor kappa B) signaling, and enhanced the expression of a number of anti-inflammatory microRNAs. Mechanistically, ADAR1 interacted with Drosha to promote its degradation, which attenuated Drosha-DGCR8 (DiGeorge syndrome critical region 8) interaction, and consequently inhibited pri- to pre-microRNA processing of microRNAs targeting IKKβ, resulting in an increased IKKβ (inhibitor of nuclear factor kappa-B) expression and enhanced NF-κB signaling. Significantly, ADAR1 was induced in macrophages and interacted with Drosha in human AAA lesions. Reconstitution of ADAR1-deficient, but not the wild type, human monocytes to immunodeficient mice blocked the aneurysm formation in transplanted human arteries. Macrophage ADAR1 promotes aneurysm formation in both mouse and human arteries through a novel mechanism, that is, Drosha protein degradation, which inhibits the processing of microRNAs targeting NF-kB signaling and thus elicits macrophage-mediated vascular inflammation in AAA.

Differences between inflammatory cells infiltrated into tunica intima, media, and adventitia of ascending aortic aneurysms within diabetic and hypertensive patients.

The risk factors that are the most significant for the development of most cardiovascular diseases are arterial hypertension (AH), type 2 diabetes (DM), and inflammation. However, for the development of aortic aneurysms, DM is not one of them. Our study aimed to evaluate the difference between inflammatory infiltration in three individual layers of the ascending aortic aneurysm within diabetic and hypertensive patients. Forty-five patients aged 36 to 80 were divided into a group with diabetic patients without AH (group DM, N=8) and hypertensive patients without DM (group AH, N=37). For the histological analysis, aortic aneurysms were stained with hematoxylin eosin and Movat. We used immunochemical methods to detect pro- (M1), anti-inflammatory (M2) macrophages, T-helper, T-killer cells, B cells, and plasma cells. Statistical analysis was done by independent-samples Kruskal-Wallis test adjusted by Bonferroni correction for multiple tests (P<0.05). We found no difference in the volume density of collagen, elastin, vascular smooth muscle cells (VSMC), and ground substance between groups. In the DM group, there were significantly fewer M2, T-helpers, and T-killers in the media than in the intima and the adventitia (P<0.05). There were no significant differences in the number of M1, B, and plasma cells between all three vascular layers (P<0.05). In the AH group, there were significantly fewer B and plasma cells, T-helper, T-killer cells, M1, and M2 in the media than in the intima and adventitia (P<0.05). Our results conclude that the tunica media in the aneurismal wall of the AH group retained immune privilege. In contrast, in the DM group, all three layers were immune-privileged.

Differences between inflammatory cells infiltrated into tunica intima, media, and adventitia of ascending aortic aneurysms within diabetic and hypertensive patients.

The risk factors that are the most significant for the development of most cardiovascular diseases are arterial hypertension (AH), type 2 diabetes (DM), and inflammation. However, for the development of aortic aneurysms, DM is not one of them. Our study aimed to evaluate the difference between inflammatory infiltration in three individual layers of the ascending aortic aneurysm within diabetic and hypertensive patients. Forty-five patients aged 36 to 80 were divided into a group with diabetic patients without AH (group DM, N=8) and hypertensive patients without DM (group AH, N=37). For the histological analysis, aortic aneurysms were stained with hematoxylin eosin and Movat. We used immunochemical methods to detect pro- (M1), anti-inflammatory (M2) macrophages, T-helper, T-killer cells, B cells, and plasma cells. Statistical analysis was done by independent-samples Kruskal-Wallis test adjusted by Bonferroni correction for multiple tests (P<0.05). We found no difference in the volume density of collagen, elastin, vascular smooth muscle cells (VSMC), and ground substance between groups. In the DM group, there were significantly fewer M2, T-helpers, and T-killers in the media than in the intima and the adventitia (P<0.05). There were no significant differences in the number of M1, B, and plasma cells between all three vascular layers (P<0.05). In the AH group, there were significantly fewer B and plasma cells, T-helper, T-killer cells, M1, and M2 in the media than in the intima and adventitia (P<0.05). Our results conclude that the tunica media in the aneurismal wall of the AH group retained immune privilege. In contrast, in the DM group, all three layers were immune-privileged.

Insulin Dependence Is Associated With Poor Long-term Outcomes But Equivalent Perioperative Outcomes Following AAA Repair

While diabetes is often a risk factor for vascular disease, its protective effects on abdominal aortic aneurysm (AAA) development have been well documented. Much less is known about the impact of diabetes-and in particular insulin dependence-on long-term outcomes following AAA repair. We aim to evaluate the role of diabetes on perioperative outcomes, mortality, and reintervention following both endovascular and open AAA repair.

Nicotinamide Mononucleotide Alleviates Angiotensin II-Induced Human Aortic Smooth Muscle Cell Senescence in a Microphysiological Model.

The occurrence and development of aortic aneurysms are accompanied by senescence of human aortic smooth muscle cells (HASMCs). Because the mechanism of HASMC senescence has not been fully elucidated, the efficacy of various antisenescence treatments varies. Decreased nicotinamide adenine dinucleotide (NAD + ) levels are one of the mechanisms of cell senescence, and there is a lack of evidence on whether increasing NAD + levels could alleviate HASMC senescence and further retard the progression of aortic aneurysms.We constructed an HASMC-based organ-on-a-chip microphysiological model. RNA sequencing was performed on cell samples from the vehicle control and angiotensin II groups to explore biological differences. We detected cellular senescence markers and NAD + levels in HASMC-based organ-on-a-chip. Subsequently, we pretreated HASMC using the synthetic precursor of NAD + , nicotinamide mononucleotide, and angiotensin II treatment, and used rhythmic stretching to investigate whether nicotinamide mononucleotide could delay HASMC senescence.The HASMC-based organ-on-a-chip model can simulate the biomechanical microenvironment of HASMCs in vivo, and the use of angiotensin II in the model replicated senescence in HASMCs. The senescence of HASMCs was accompanied by downregulation of the expression level of nicotinamide phosphoribosyltransferase and NAD + . Pretreatment with nicotinamide mononucleotide significantly increased the NAD + level and alleviated the senescence of HASMCs, but did not change the expression level of nicotinamide phosphoribosyltransferase.Our study provides a complementary research platform between traditional cell culture and animal experiments to explore HASMC senescence in aortic aneurysms. Furthermore, it provides evidence for NAD + boosting therapy in the clinical treatment of aortic aneurysms.

The Presence of Ascending Aortic Dilatation in Patients Undergoing Transcatheter Aortic Valve Replacement Is Negatively Correlated with the Presence of Diabetes Mellitus and Does Not Impair Post-Procedural Outcomes.

A total of 179 patients with severe AS and an available computed tomography were included in this retrospective study. AA was measured, and dilatation was defined as a diameter ≥ 40 mm. Thirty-two patients had dilatation of the AA. A further 32 patients from the present population with a normal AA were matched to the aortic dilatation group with respect to gender, age, body mass index and body surface area, and the resulting study groups were compared with each other. In addition to echocardiographic and clinical characteristics, the expression of cardiovascular biomarkers such as brain natriuretic peptide (BNP), soluble suppression of tumorigenicity-2 (sST2), growth/differentiation of factor-15 (GDF-15), heart-type fatty-acid binding protein (H-FABP), insulin-like growth factor binding protein 2 (IGF-BP2) and soluble urokinase-type plasminogen activator receptor (suPAR) was analyzed. Kaplan-Meier curves for short- and long-term survival were obtained, and Pearson's and Spearman's correlations were calculated to identify the predictors between the diameter of the AA and clinical parameters. A total of 19% of the total cohort had dilatation of the AA. The study group with an AA diameter ≥ 40 mm showed a significantly low comorbidity with respect to diabetes mellitus in contrast to the comparison cohort with an AA diameter < 40 mm (p = 0.010). This result continued in the correlation analyses performed, as the presence of diabetes mellitus correlated negatively not only with the diameter of the AA (r = -0.404; p = 0.001) but also with the presence of aortic dilatation (r = -0.320; p = 0.010). In addition, the presence of AA dilatation after TAVR was shown to have no differences in terms of patient survival at 1, 3 and 5 years. There were no relevant differences in the cardiovascular biomarkers studied between the patients with dilated and normal AAs. The presence of AA dilatation before successful TAVR was not associated with a survival disadvantage at the respective follow-up intervals of 1, 3 and 5 years. Diabetes mellitus in general seemed to have a protective effect against the development of AA dilatation or aneurysm in patients with severe AS.

Molecular Mechanisms in Genetic Aortopathy-Signaling Pathways and Potential Interventions.

Thoracic aortic disease affects people of all ages and the majority of those aged &lt;60 years have an underlying genetic cause. There is presently no effective medical therapy for thoracic aneurysm and surgery remains the principal intervention. Unlike abdominal aortic aneurysm, for which the inflammatory/atherosclerotic pathogenesis is well established, the mechanism of thoracic aneurysm is less understood. This paper examines the key cell signaling systems responsible for the growth and development of the aorta, homeostasis of endothelial and vascular smooth muscle cells and interactions between pathways. The evidence supporting a role for individual signaling pathways in pathogenesis of thoracic aortic aneurysm is examined and potential novel therapeutic approaches are reviewed. Several key signaling pathways, notably TGF-β, WNT, NOTCH, PI3K/AKT and ANGII contribute to growth, proliferation, cell phenotype and survival for both vascular smooth muscle and endothelial cells. There is crosstalk between pathways, and between vascular smooth muscle and endothelial cells, with both synergistic and antagonistic interactions. A common feature of the activation of each is response to injury or abnormal cell stress. Considerable experimental evidence supports a contribution of each of these pathways to aneurysm formation. Although human information is less, there is sufficient data to implicate each pathway in the pathogenesis of human thoracic aneurysm. As some pathways i.e., WNT and NOTCH, play key roles in tissue growth and organogenesis in early life, it is possible that dysregulation of these pathways results in an abnormal aortic architecture even in infancy, thereby setting the stage for aneurysm development in later life. Given the fine tuning of these signaling systems, functional polymorphisms in key signaling elements may set up a future risk of thoracic aneurysm. Multiple novel therapeutic agents have been developed, targeting cell signaling pathways, predominantly in cancer medicine. Future investigations addressing cell specific targeting, reduced toxicity and also less intense treatment effects may hold promise for effective new medical treatments of thoracic aortic aneurysm.

CLINICAL CONSEQUENCES DEPENDENCE OF ACUTE CORONARY SYNDROME INVASIVE TREATMENT ON THE CHARACTERISTICS OF SEGMENTAL INJURY OF CORONARY ARTERIES

Cardiovascular diseases are the main cause of mortality and disability factors. Prediction of the possible consequences of treatment, based on data on the features of anatomical localization of lesions, will obviously be able to improve the quality of treatment and reduce the level of disability. Optimization of interventional treatment methods depending on the coronary vasculature anatomical features, the development of collateral blood flow is aimed at the implementation of a personalized approach to the medical care.The aim of the work was to optimize interventional treatment of patients with acute coronary syndrome by studying the features of segmental formation of coronary arteries. The study analyzed the data of 121 patients with acute coronary syndrome who underwent coronary angiography with radial access and stenting of the infarct-related artery. Determination of coronary artery segments was performed according to the numbering method proposed by the American Heart Association. The severity of coronary artery disease was determined according to the Gensini scale. 88.43% of the patients included in the study had multivessel coronary disease. A relation was established between the lesion of segment 10 (r=0.312, p&lt;0.001), segment 11 (r=0.211, p=0.015) and segment 14 (r=0.228, p=0.008) with the occurrence of MI recurrences. In case of diagonal artery lesions (D2), recurrences of MI occurred in 40.0% of patients, in the circumflex artery: 14 segment – 25.0%, and 11segment – 14.29%. In the remaining cases, the proportion of MI recurrences was significantly lower (from 2.67 to 8.86%). Analysis of the segmental localization of the infarct-related area of the coronary artery shows that there are certain "typical" areas of lesions in right and left coronary arteries - the middle section of the right coronary artery and the proximal section of the anterior interventricular branch of the left coronary artery. We also consider the obtained data to be important for predicting the risk of myocardial infarction recurrence, which turned out to be greater with occlusion of the 10th, 11th, and 14th segments of the coronary artery. In patients over 63 years of age, attention should be paid to the fourth segment of the right coronary artery, since occlusion of this section occurs more often in this age group. Atherosclerotic injury to the proximal part of the right coronary artery usually is not accompanied by prodromal syndrome of myocardial infarction in the form of unstable angina pectoris.The number of implanted stents did not reliably affect mortality and long-term survival. Correlations of lesions of certain segments of coronary vessels with previous manifestations of unstable angina pectoris and recurrent course, age and gender differences, presence of comorbidity, especially with arterial hypertension and diabetes have been established. Structural and functional changes in the myocardium were found to be the most severe in pathology of the left main stem. The relation between the lesion of the left main stem and the deterioration in the left ventricle ejection fraction (r=-0.244, p=0.005), the development of the left ventricle aneurysm (r=0.211, p=0.015) was established in 16.67% (in other segments - from 0 to 5.55%), rhythm disorders such as atrial fibrillation (r=0.304, p&lt;0.001) in 25.00% (in other segments – from 2.17 to 9.52%), were more often accompanied by acute heart failure (Killip3-4) in 17.67% (in other segments - from 0 to 7.50%).

Management of the False Lumen in Post Type A Aortic Dissection Arch Aneurysms Treated With Branched Endografts

Introduction: The treatment of chronic postdissection aneurysms of the aortic arch is a challenge. This study aims to describe false lumen management after aortic arch endovascular repair of post-type A dissection aneurysms treated with a branched endograft. Methods: In this single-center retrospective observational study, all consecutive patients undergoing endovascular treatment of aneurysmal degeneration of chronic type A aortic dissections following open repair were enrolled. The primary endpoint was maximal aortic diameter evolution measured on computed tomography angiography (CTA) performed during follow-up. Secondary endpoints included procedural success, aortic re intervention, and remodeling during follow-up. Results: Between January 2017 and June 2020, 22 patients underwent endovascular branched arch repair for post type A dissection aneurysms. Technical success was 100%. Thirteen patients (59%) had dissection involvement of at least 1 supra-aortic vessel. Midterm follow-up CTA was performed for 20 patients, 23.1 (±13.3) months after the procedure. Maximal aortic diameter at the level of the repair was decreasing in 13 (65%) patients, increasing in 2 (10%) patients, and no change was observed in 5 (25%) patients. During follow-up, 7 patients (35%) required aortic reintervention. Thoracic candy plugs were implanted for distal false lumen occlusion in 15 patients and associated with a high rate of complete remodeling (6/15 patients, 40%). Conclusion: Arch branch endografting of aneurysmal evolution of a post type A dissection aortic arch is a safe and feasible option in experienced hands. Candy plug use in favorable anatomies seems to be associated with accelerated remodeling of the aorta. Clinical Impact There are currently no recommendations on dissected supra- aortic vessels management and the use of thoracic aorta false lumen occlusion devices during endovascular repair of chronic post dissection aneurysm of the aortic arch with branched endografts. Based on our clinical experience reported in the current manuscript, we propose a treatment algorithm for the management of the false lumen in this setting.

Molecular and Cellular Mechanisms Involved in Aortic Wall Aneurysm Development.

Aortic aneurysms represent a very common pathology that can affect any segment of the aorta. These types of aneurysms can be localized on the thoracic segment or on the abdominal portion, with the latter being more frequent. Though there are similarities between thoracic and abdominal aortic aneurysms, these pathologies are distinct entities. In this article, we undertook a review regarding the different mechanisms that can lead to the development of aortic aneurysm, and we tried to identify the different manners of treatment. For a long time, aortic wall aneurysms may evolve in an asymptomatic manner, but this progressive dilatation of the aneurysm can lead to a potentially fatal complication consisting in aortic rupture. Because there are limited therapies that may delay or prevent the development of acute aortic syndromes, surgical management remains the most common manner of treatment. Even though, surgical management has improved much in the last years, thus becoming less invasive and sophisticated, the morbi-mortality linked to these therapies remains increased. The identification of the cellular and molecular networks triggering the formation of aneurysm would permit the discovery of modern therapeutic targets. Molecular and cellular mechanisms are gaining a bigger importance in the complex pathogenesis of aortic aneurysms. Future studies must be developed to compare the findings seen in human tissue and animal models of aortic aneurysm, so that clinically relevant conclusions about the aortic aneurysm formation and the pharmacological possibility of pathogenic pathways blockage can be drawn.

CCN2 deficiency in smooth muscle cells triggers cell reprogramming and aggravates aneurysm development.

Vascular smooth muscle cell (SMC) phenotypic switching is widely recognized as a key mechanism responsible for the pathogenesis of several aortic diseases, such as aortic aneurysm. Cellular communication network factor 2 (CCN2), often upregulated in human pathologies and animal disease models, exerts myriad context-dependent biological functions. However, current understanding of the role of SMC-CCN2 in SMC phenotypic switching and its function in the pathology of abdominal aortic aneurysm (AAA) is lacking. Here, we show that SMC-restricted CCN2 deficiency causes AAA in the infrarenal aorta of angiotensin II-infused (Ang II-infused) hypercholesterolemic mice at a similar anatomic location to human AAA. Notably, the resistance of naive C57BL/6 WT mice to Ang II-induced AAA formation is lost upon silencing of CCN2 in SMC. Furthermore, the pro-AAA phenotype of SMC-CCN2-KO mice is recapitulated in a different model that involves the application of elastase-β-aminopropionitrile. Mechanistically, our findings reveal that CCN2 intersects with TGF-β signaling and regulates SMC marker expression. Deficiency of CCN2 triggers SMC reprograming associated with alterations in Krüppel-like factor 4 and contractile marker expression, and this reprograming likely contributes to the development of AAA in mice. These results identify SMC-CCN2 as potentially a novel regulator of SMC phenotypic switching and AA biology.

Mechanosignals in abdominal aortic aneurysms.

Cumulative evidence has shown that mechanical and frictional forces exert distinct effects in the multi-cellular aortic layers and play a significant role in the development of abdominal aortic aneurysms (AAA). These mechanical cues collectively trigger signaling cascades relying on mechanosensory cellular hubs that regulate vascular remodeling programs leading to the exaggerated degradation of the extracellular matrix (ECM), culminating in lethal aortic rupture. In this review, we provide an update and summarize the current understanding of the mechanotransduction networks in different cell types during AAA development. We focus on different mechanosensors and stressors that accumulate in the AAA sac and the mechanotransduction cascades that contribute to inflammation, oxidative stress, remodeling, and ECM degradation. We provide perspectives on manipulating this mechano-machinery as a new direction for future research in AAA.

Group 2 Innate Lymphoid Cells Protect Mice from Abdominal Aortic Aneurysm Formation via IL5 and Eosinophils.

Development of abdominal aortic aneurysms (AAA) enhances lesion group-2 innate lymphoid cell (ILC2) accumulation and blood IL5. ILC2 deficiency in Rorafl/fl Il7rCre/+ mice or induced ILC2 depletion in Icosfl-DTR-fl/+ Cd4Cre/+ mice expedites AAA growth, increases lesion inflammation, but leads to systemic IL5 and eosinophil (EOS) deficiency. Mechanistic studies show that ILC2 protect mice from AAA formation via IL5 and EOS. IL5 or ILC2 from wild-type (WT) mice, but not ILC2 from Il5-/- mice induces EOS differentiation in bone-marrow cells from Rorafl/fl Il7rCre/+ mice. IL5, IL13, and EOS or ILC2 from WT mice, but not ILC2 from Il5-/- and Il13-/- mice block SMC apoptosis and promote SMC proliferation. EOS but not ILC2 from WT or Il5-/- mice block endothelial cell (EC) adhesion molecule expression, angiogenesis, dendritic cell differentiation, and Ly6Chi monocyte polarization. Reconstitution of WT EOS and ILC2 but not Il5-/- ILC2 slows AAA growth in Rorafl/fl Il7rCre/+ mice by increasing systemic EOS. Besides regulating SMC pathobiology, ILC2 play an indirect role in AAA protection via the IL5 and EOS mechanism.

Fluid–structure interaction simulation for studying hemodynamics and rupture risk of patient-specific intracranial aneurysms

Purpose The role of regional hemodynamics in intracranial aneurysms (IAs) hemodynamics and rupture risk has been widely discussed based on numerical models over the past decades. The aim of this paper is to investigate hemodynamics and rupture risk with a complicated IA model. Methods Fluid-structure interaction (FSI) simulations were performed to quantify the hemodynamic characteristics of the established IA models. Hemodynamic parameters, including wall shear stress (WSS), flow velocity, and flow pattern, were calculated and analyzed. Results In this paper, the risk assessment of intracranial aneurysms focuses on the mechanical properties of blood flow and blood vessel walls. Vortex flow and concentrated impact field during blood flow play a decisive role in the rupture and development of aneurysms. The uneven distribution of wall shear stress on the vessel wall has a great influence on growth and rupture. By observing the simulation results of rigid walls, risks can be predicted efficiently and accurately. Conclusions This paper focuses on the relationship between hemodynamics and ruptures risk with a double intracranial aneurysms disease mode and provides a new perspective on the treatment of intracranial aneurysms.