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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 -
Journal of Molecular and Cellular... Oct 2022Aortic aneurysm and dissection (AAD) is a life-threatening medical condition associated with high morbidity and mortality rates. Important mechanisms underlying AAD are... (Review)
Review
Aortic aneurysm and dissection (AAD) is a life-threatening medical condition associated with high morbidity and mortality rates. Important mechanisms underlying AAD are the dysregulation of vascular homeostasis and adverse remodeling. Vascular homeostasis maintains normal physiological function. Various physical, chemical, biological, and other internal or external environmental changes dysregulate vascular homeostasis, leading to vascular degeneration and aggravated aortic injury. This process is dependent on the communication between homeostatic mechanisms and the extracellular environment, such as local inflammatory cytokines, vasoactive substances, and hemodynamics. In this article, we summarize recent reports by Chinese researchers who studied the pathogenic mechanisms of AAD mainly from the perspective of communication of the extracellular environment with vascular homeostasis and improving diagnostic methods and therapeutic options for patients with AAD. This review aims to provide a roadmap for AAD that encompasses its pathogenesis and clinical aspects. We hope to facilitate future studies on the development of effective treatments and preventive therapies, and thus improve patient outcomes.
Topics: Aortic Dissection; Aortic Aneurysm; Cytokines; Homeostasis; Humans; Muscle, Smooth, Vascular
PubMed: 35798048
DOI: 10.1016/j.yjmcc.2022.06.010 -
Interactive Cardiovascular and Thoracic... Jun 2022
Topics: Aortic Aneurysm; Aortic Aneurysm, Thoracic; Humans
PubMed: 35640563
DOI: 10.1093/icvts/ivac141 -
American Journal of Physiology. Heart... Dec 2022Phospholipase Cε (PLCε) is a phospholipase C isoform with a wide range of physiological functions. It has been implicated in aortic valve disorders, but its role in...
Phospholipase Cε (PLCε) is a phospholipase C isoform with a wide range of physiological functions. It has been implicated in aortic valve disorders, but its role in frequently associated aortic disease remains unclear. To determine the role of PLCε in thoracic aortic aneurysm and dissection (TAAD) we used PLCε-deficient mice, which develop aortic valve insufficiency and exhibit aortic dilation of the ascending thoracic aorta and arch without histopathological evidence of injury. Fourteen days of infusion of and mice with angiotensin II (ANG II), which induces aortic dilation and dissection, led to sudden death secondary to ascending aortic dissection in 43% of versus 5% of mice ( < 0.05). Medial degeneration and TAAD were detected in 80% of compared with 10% of mice ( < 0.05) after 4 days of ANG II. Treatment with ANG II markedly increased PLCε expression within the ascending aortic adventitia. Total RNA sequencing demonstrated marked upregulation of inflammatory and fibrotic pathways mediated by interleukin-1β, interleukin-6, and tumor necrosis factor-α. In silico analysis of whole exome sequences of 258 patients with type A dissection identified 5 patients with nonsynonymous variants. Our data suggest that PLCε deficiency plays a role in the development of TAAD and aortic insufficiency. We describe a novel phenotype by which PLCε deficiency predisposes to aortic valve insufficiency and ascending aortic aneurysm, dissection, and sudden death in the setting of ANG II-mediated hypertension. We demonstrate variants in patients with type A aortic dissection and aortic insufficiency, suggesting that may also play a role in human aortic disease. This finding is of very high significance because it has not been previously demonstrated that PLCε directly mediates aortic dissection.
Topics: Humans; Mice; Animals; Aortic Valve Insufficiency; Aneurysm, Ascending Aorta; Mice, Inbred C57BL; Aortic Aneurysm; Aortic Dissection; Angiotensin II; Hypertension; Death, Sudden; Aortic Aneurysm, Thoracic
PubMed: 36367690
DOI: 10.1152/ajpheart.00262.2022 -
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 -
American Journal of Physiology. Heart... Mar 2020Aortic 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... (Review)
Review
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.
Topics: Aortic Aneurysm; Disease Progression; Extracellular Matrix; Humans; Matrix Metalloproteinases; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Vascular Remodeling
PubMed: 32083977
DOI: 10.1152/ajpheart.00621.2019 -
European Heart Journal. Cardiovascular... Nov 2022Conotruncal anomalies share common embryogenic defects of the outflow tracts and great arteries, which result in a predisposition to aortic aneurysms. The purpose of...
AIMS
Conotruncal anomalies share common embryogenic defects of the outflow tracts and great arteries, which result in a predisposition to aortic aneurysms. The purpose of this study was to describe the prevalence and risk of progressive aortic aneurysms in adults with conotruncal anomalies.
METHODS AND RESULTS
Retrospective study of adults with conotruncal anomalies that underwent cross-sectional imaging 2003-20. Aneurysm was defined as aortic root/mid-ascending aorta >2.1 mm/m2/>1.9 mm/m2, progressive aneurysm as increase by >2 mm, and severe aneurysm as dimension >50 mm. Of 2261 patients (38 ± 12 years; male 58%), 1167 (52%) had an aortic aneurysm, and 205 (14%) had a severe aortic aneurysm. Mean annual increase in aortic root/mid-ascending aorta was 0.3 ± 0.1 mm/0.2 ± 0.1 mm. The 3-, 5-, and 7-year cumulative incidence of the progressive aortic aneurysm was 4%, 7%, and 9%, respectively. The rate of aneurysm growth decreased with age, with no significant growth after age 40 years. There was an excellent correlation between aortic indices from cross-sectional imaging and echocardiography. Of 950 females, 184 had ≥1 pregnancy, and 81 (44%) of the 184 patients had aortic aneurysm prior to pregnancy. There was no aortic dissection or progression of the aortic aneurysm during pregnancy. Overall, there was no aortic dissection during 7984 patient-years of follow-up.
CONCLUSIONS
Aortic aneurysm was common in patients with conotruncal anomalies. However, the risk of progressive aneurysm or dissection was low. Collectively, these data suggest a benign natural history and perhaps a less frequent need for cross-sectional imaging. Further studies are required to determine the optimal timing for surgical intervention in this population.
Topics: Adult; Pregnancy; Female; Humans; Male; Aortic Aneurysm, Thoracic; Prevalence; Retrospective Studies; Aortic Aneurysm; Aortic Dissection
PubMed: 34939103
DOI: 10.1093/ehjci/jeab273 -
BMC Cardiovascular Disorders Sep 2021Aortic aneurysm (AA) and aortic dissection (AD) are major life-threatening diseases around the world. AA is a localized or diffuse dilation of the aorta, while AD is the... (Review)
Review
Aortic aneurysm (AA) and aortic dissection (AD) are major life-threatening diseases around the world. AA is a localized or diffuse dilation of the aorta, while AD is the separation of the layers creating a false lumen within the aortic wall. Fluoroquinolones (FQ) remain one of the most important kind of antibiotics and have a wider clinical use and broad antibacterial spectrum. FQ were also reported to treat infected AA. The most common adverse events (AEs) of FQ are mild and reversible, like headaches, diarrhea and nausea. Due to FQ-related serious AEs, such as tendonitis and tendon rupture, chondrotoxicity, or retinal detachment, QT-prolongation and dysglycemia, the United States Food and Drug Administration (FDA) issued a black box warning for FQ for systemic use in 2016 and updated warnings for FQ several times since then. Of note, in December 2018, FDA issued several "black box warnings" against FQ with the latest safety announcement warning about an increased risk of ruptures in the aorta blood vessel in certain patients. Recently, many studies have indicated an association between FQ and an increase risk of AA and AD. However, the exact mechanism of FQ-induced AA/AD remains unclear. This review aims to highlight the latest research progress of the alarming association between FQ and AA/AD. Moreover, molecular mechanisms of FQ in increasing risk of AA and AD are explored. Hopefully, this review can provide novel insights into FQ-increased the risk of AA/AD and a starting place for stewardship interventions.
Topics: Adult; Aged; Aortic Dissection; Animals; Anti-Bacterial Agents; Antimicrobial Stewardship; Aortic Aneurysm; Female; Fluoroquinolones; Humans; Incidence; Male; Middle Aged; Risk Assessment; Risk Factors
PubMed: 34583637
DOI: 10.1186/s12872-021-02258-1 -
Experimental & Molecular Medicine Dec 2019Aortic aneurysm is an asymptomatic disease with dire outcomes if undiagnosed. Aortic aneurysm rupture is a significant cause of death worldwide. To date, surgical repair... (Review)
Review
Aortic aneurysm is an asymptomatic disease with dire outcomes if undiagnosed. Aortic aneurysm rupture is a significant cause of death worldwide. To date, surgical repair or endovascular repair (EVAR) is the only effective treatment for aortic aneurysm, as no pharmacological treatment has been found effective. Aortic aneurysm, a focal dilation of the aorta, can be formed in the thoracic (TAA) or the abdominal (AAA) region; however, our understanding as to what determines the site of aneurysm formation remains quite limited. The extracellular matrix (ECM) is the noncellular component of the aortic wall, that in addition to providing structural support, regulates bioavailability of an array of growth factors and cytokines, thereby influencing cell function and behavior that ultimately determine physiological or pathological remodeling of the aortic wall. Here, we provide an overview of the ECM proteins that have been reported to be involved in aortic aneurysm formation in humans or animal models, and the experimental models for TAA and AAA and the link to ECM manipulations. We also provide a comparative analysis, where data available, between TAA and AAA, and how aberrant ECM proteolysis versus disrupted synthesis may determine the site of aneurysm formation.
Topics: Animals; Aorta; Aortic Aneurysm; Aortic Aneurysm, Abdominal; Aortic Aneurysm, Thoracic; Extracellular Matrix; Humans
PubMed: 31857579
DOI: 10.1038/s12276-019-0286-3 -
JAMA Nov 2022
Topics: Humans; Aortic Aneurysm; Aortic Aneurysm, Abdominal; Aortic Rupture; Data Science; Mass Screening; Risk Factors; Ultrasonography
PubMed: 36378223
DOI: 10.1001/jama.2022.9164