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JCI Insight Sep 2023Inadequate adaption to mechanical forces, including blood pressure, contributes to development of arterial aneurysms. Recent studies have pointed to a mechanoprotective...
Inadequate adaption to mechanical forces, including blood pressure, contributes to development of arterial aneurysms. Recent studies have pointed to a mechanoprotective role of YAP and TAZ in vascular smooth muscle cells (SMCs). Here, we identified reduced expression of YAP1 in human aortic aneurysms. Vascular SMC-specific knockouts (KOs) of YAP/TAZ were thus generated using the integrin α8-Cre (Itga8-Cre) mouse model (i8-YT-KO). i8-YT-KO mice spontaneously developed aneurysms in the abdominal aorta within 2 weeks of KO induction and in smaller arteries at later times. The vascular specificity of Itga8-Cre circumvented gastrointestinal effects. Aortic aneurysms were characterized by elastin disarray, SMC apoptosis, and accumulation of proteoglycans and immune cell populations. RNA sequencing, proteomics, and myography demonstrated decreased contractile differentiation of SMCs and impaired vascular contractility. This associated with partial loss of myocardin expression, reduced blood pressure, and edema. Mediators in the inflammatory cGAS/STING pathway were increased. A sizeable increase in SOX9, along with several direct target genes, including aggrecan (Acan), contributed to proteoglycan accumulation. This was the earliest detectable change, occurring 3 days after KO induction and before the proinflammatory transition. In conclusion, Itga8-Cre deletion of YAP and TAZ represents a rapid and spontaneous aneurysm model that recapitulates features of human abdominal aortic aneurysms.
Topics: Animals; Humans; Mice; Aorta, Abdominal; Aortic Aneurysm; Aortic Aneurysm, Abdominal; Disease Models, Animal; Muscle, Smooth, Vascular
PubMed: 37561588
DOI: 10.1172/jci.insight.170845 -
VASA. Zeitschrift Fur Gefasskrankheiten Jan 2023
Topics: Humans; Aortic Aneurysm; Aortic Aneurysm, Abdominal; Neoplasms; Blood Vessel Prosthesis Implantation
PubMed: 36617969
DOI: 10.1024/0301-1526/a001046 -
Brazilian Journal of Cardiovascular... May 2022Tuberculous aortic aneurysm (TBAA) is an exceedingly rare but severe manifestation of tuberculosis, with a high risk of sudden rupture of the aorta in absence of medical... (Review)
Review
INTRODUCTION
Tuberculous aortic aneurysm (TBAA) is an exceedingly rare but severe manifestation of tuberculosis, with a high risk of sudden rupture of the aorta in absence of medical or surgical intervention. This review aimed to provide a detailed understanding of TBAA, including its associated complications, affected population, treatment measures, and outcomes.
METHODS
Case studies and relevant research articles were analyzed to understand the recent advances in medical scientific knowledge on TBAA. Recent clinical case reports on TBAA were searched from the year 2010 to 2020.
RESULTS
Case reports indicated a higher prevalence of TBAA in the male population. The most affected age group was 15 to 79 years. The most common treatment for TBAA included surgery followed by antituberculous medication. The case reports discussed in this review reflected open surgery, endovascular repair, coil embolization, laparotomy, aortic valve and root replacement as some of the surgical procedures used depending on the complication and type of aneurysm. The treatment outcome was considered effective in most cases.
CONCLUSION
Postoperative chemotherapy and medications reduce the risk of severity. Early diagnosis of TBAA is imperative, followed by surgical resection and postoperative antituberculous medication with careful follow-up to prevent relapse.
Topics: Adolescent; Adult; Aged; Aortic Aneurysm; Aortic Aneurysm, Abdominal; Blood Vessel Prosthesis; Endovascular Procedures; Humans; Male; Middle Aged; Postoperative Complications; Treatment Outcome; Tuberculosis; Young Adult
PubMed: 35605220
DOI: 10.21470/1678-9741-2020-0611 -
International Journal of Molecular... Jul 2023Vascular smooth muscle cells (VSMCs) are the predominant cell type in the medial layer of the aorta, which plays a critical role in the maintenance of aortic wall... (Review)
Review
Vascular smooth muscle cells (VSMCs) are the predominant cell type in the medial layer of the aorta, which plays a critical role in the maintenance of aortic wall integrity. VSMCs have been suggested to have contractile and synthetic phenotypes and undergo phenotypic switching to contribute to the deteriorating aortic wall structure. Recently, the unprecedented heterogeneity and diversity of VSMCs and their complex relationship to aortic aneurysms (AAs) have been revealed by high-resolution research methods, such as lineage tracing and single-cell RNA sequencing. The aortic wall consists of VSMCs from different embryonic origins that respond unevenly to genetic defects that directly or indirectly regulate VSMC contractile phenotype. This difference predisposes to hereditary AAs in the aortic root and ascending aorta. Several VSMC phenotypes with different functions, for example, secreting VSMCs, proliferative VSMCs, mesenchymal stem cell-like VSMCs, immune-related VSMCs, proinflammatory VSMCs, senescent VSMCs, and stressed VSMCs are identified in non-hereditary AAs. The transformation of VSMCs into different phenotypes is an adaptive response to deleterious stimuli but can also trigger pathological remodeling that exacerbates the pathogenesis and development of AAs. This review is intended to contribute to the understanding of VSMC diversity in health and aneurysmal diseases. Papers that give an update on VSMC phenotype diversity in health and aneurysmal disease are summarized and recent insights on the role of VSMCs in AAs are discussed.
Topics: Humans; Muscle, Smooth, Vascular; Cells, Cultured; Aorta; Aortic Aneurysm; Phenotype; Myocytes, Smooth Muscle
PubMed: 37511460
DOI: 10.3390/ijms241411701 -
European Journal of Vascular and... Aug 2020
Review
Topics: Aortic Aneurysm; Female; Genetic Counseling; Genetic Predisposition to Disease; Heredity; Humans; Pedigree; Preconception Care; Pregnancy; Pregnancy Complications, Cardiovascular; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 32409015
DOI: 10.1016/j.ejvs.2020.03.052 -
The Journal of Thoracic and... Apr 2021
Topics: Adult; Aged; Aged, 80 and over; Anatomy, Cross-Sectional; Aorta; Aortic Aneurysm; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Tomography, X-Ray Computed; Young Adult
PubMed: 32792149
DOI: 10.1016/j.jtcvs.2020.06.137 -
Interactive Cardiovascular and Thoracic... Jun 2022
Topics: Aortic Aneurysm; Aortic Aneurysm, Thoracic; Humans
PubMed: 35640563
DOI: 10.1093/icvts/ivac141 -
Deutsches Arzteblatt International Nov 2015Abdominal and thoracic aortic aneurysms are diagnosed in 40 and 10 to 15 out of 100 000 persons per year, respectively. Fenestrated (fEVAR) and branched (bEVAR) stent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Abdominal and thoracic aortic aneurysms are diagnosed in 40 and 10 to 15 out of 100 000 persons per year, respectively. Fenestrated (fEVAR) and branched (bEVAR) stent grafts have been developed for abdominal juxtarenal and thoracoabdominal aneurysms. We discuss the patency and complication rates of fEVAR and bEVAR procedures and compare them with the outcome of open surgery.
METHODS
This review is based on pertinent publications from 2011 to 2014 that were retrieved by a selective literature search. The clinical outcomes of case series involving a total of more than 1500 patients are presented. The discussion takes account of recommendations contained in the literature and the authors' own experience.
RESULTS
Open surgery and aortic stent grafting have not been compared in any randomized trial to date. We identified 7 clinical series that included a total of 1270 fEVAR patients and 5 with a total of 408 bEVAR patients. The perioperative mortality after fEVAR procedures was 0-4%. Spinal cord ischemia arose in 1% of cases. The stent patency rate in visceral vessels ranged from 93 to 98%. bEVAR procedures were associated with both higher mortality (4-7%) and more common spinal cord ischemia (4-13%). 5-8% of all patients needed dialysis perioperatively, and the stent patency rate in visceral vessels was 94-97%. Preoperative renal insufficiency was a risk factor for peri-interventional death. Impaired renal function after fEVAR/bEVAR procedures was mainly associated with intermittent lower limb ischemia.
CONCLUSION
The results of fEVAR/bEVAR procedures in the last 5 years are similar to those of open surgery. The high postoperative rate of spinal cord ischemia remains a serious problem in the endovascular treatment of thoracoabdominal aortic aneurysms. The decision to implant a stent graft by an endovascular approach or to treat surgically should be made on a case-to-case basis in an interdisciplinary vascular conference.
Topics: Aortic Aneurysm; Blood Vessel Prosthesis; Humans; Postoperative Complications; Prevalence; Prosthesis Design; Risk Factors; Stents; Survival Rate; Treatment Outcome
PubMed: 26667980
DOI: 10.3238/arztebl.2015.0816 -
Journal of Nuclear Cardiology :... Aug 2017Aneurysms of the thoracic and abdominal aorta are common and can be associated with significant morbidity and mortality when complications, including dissection,... (Review)
Review
Aneurysms of the thoracic and abdominal aorta are common and can be associated with significant morbidity and mortality when complications, including dissection, rupture, or thrombosis, occur. Current approaches to diagnosis and risk stratification rely on measurements of aneurysm size and rate of growth, often using various imaging modalities, which may be suboptimal in identifying patients at the highest and lowest risk of complications. Targeting the biological processes underlying aneurysm formation and expansion with molecular imaging offers an exciting opportunity to characterize aortic aneurysms beyond size and address current gaps in our approach to diagnosis and treatment. In this review, we summarize the epidemiology and biology of aortic aneurysms and highlight the role of molecular imaging in furthering our understanding of aneurysm pathogenesis and its potential future role in guiding management.
Topics: Aortic Aneurysm; Humans; Molecular Imaging; Multimodal Imaging; Risk Assessment
PubMed: 28447279
DOI: 10.1007/s12350-017-0883-2 -
International Heart Journal Nov 2022Sinus of Valsalva aneurysm (SVA) is a rare cardiovascular disease with male predominance. Recently, an association with aortic aneurysm and SVA has been revealed in...
Sinus of Valsalva aneurysm (SVA) is a rare cardiovascular disease with male predominance. Recently, an association with aortic aneurysm and SVA has been revealed in periventricular nodular heterotopia patients with loss-of-function Filamin A (FLNA) mutations, which were located on chromosome X and almost exclusively affect females.Among patients hospitalized for aortic surgery with aortic root diameter over 4.0 cm, next-generation sequencing was performed to investigate 30 candidate genes related to inherited aortic aneurysm syndromes and familial thoracic aortic aneurysm and dissection. The present report reviewed an electronic case database and identified two female cases of unruptured SVA with heterozygous FLNA truncating mutations.Case 1 displaying a rare SVA phenotype involving left and noncoronary sinus harbored a nonsense variant p.Tyr1720Ter/c.5160C > G. Case 2 displayed right and noncoronary SVA with predominantly enlarged right coronary sinus, posterior mitral valve prolapse, and harbored a frameshift variant p.Val1724fs*68/c.5171_5172delTG. Both novel mutations resulted in the premature termination of filamin A with the loss of functional Rod 2 and dimerization region.The present report raised the possibility of the presence of a cardiovascular onset form in the spectrum of FLNA hereditary diseases. The association between SVA and loss-of-function FLNA mutations indicates a unique etiology and pathogenesis among female patients, which requires further investigation to establish the linkage between FLNA variants and a wide spectrum of phenotypes.
Topics: Male; Female; Humans; Filamins; Sinus of Valsalva; Aortic Aneurysm; Phenotype; Aortic Aneurysm, Thoracic
PubMed: 36372407
DOI: 10.1536/ihj.22-156