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Medical Science Monitor : International... Feb 2024Aortic root aneurysms are one of the most common aortic root diseases, involving the aortic valve, aortic sinus, bilateral coronary arteries, and part of the ascending... (Review)
Review
Aortic root aneurysms are one of the most common aortic root diseases, involving the aortic valve, aortic sinus, bilateral coronary arteries, and part of the ascending aorta. It is a life-threatening aortic disease with a high mortality rate of approximately 90%, due to aortic aneurysm rupture. Aortic valve insufficiency is one of the most common complications of aortic root aneurysms that can lead to acute left heart failure. The etiology of aortic root aneurysms is not yet completely clear and is mainly related to genetic diseases, such as Marfan syndrome and atherosclerosis. It can also occur secondary to aortic valve stenosis or a bivalve deformity. Surgery is the primary treatment for aortic root aneurysms, and aortic root replacement is a classic surgical method. However, the incidences of perioperative complications and mortality are relatively high, particularly in high-risk patients. In recent years, the anatomical structure of the aortic root has been gradually refined, and an in-depth understanding of root aneurysms has led to individualized treatment methods. Conservative drug therapy (ß-receptor blockers, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers), Bentall and modified Bentall surgeries (Button technology, Cabrol surgery, and modified Cabrol surgery), valve-sparing aortic root replacement (David and Yacoub), personalized external aortic root support, and endovascular intervention therapy have significantly improved the perioperative and long-term survival rates of patients with aortic root aneurysms. However, different treatment methods have their own advantages and disadvantages. This review aimed to summarize the current research progress and treatment of aortic root aneurysms.
Topics: Humans; Aortic Root Aneurysm; Aorta; Aortic Aneurysm, Thoracic; Marfan Syndrome; Aortic Valve Insufficiency; Aortic Valve; Aortic Diseases; Treatment Outcome
PubMed: 38332569
DOI: 10.12659/MSM.943216 -
Clinical Science (London, England :... Jun 2023Angiopoietin-like protein 8 (ANGPTL8) plays important roles in lipid metabolism, glucose metabolism, inflammation, and cell proliferation and migration. Clinical studies...
Angiopoietin-like protein 8 (ANGPTL8) plays important roles in lipid metabolism, glucose metabolism, inflammation, and cell proliferation and migration. Clinical studies have indicated that circulating ANGPTL8 levels are increased in patients with thoracic aortic dissection (TAD). TAD shares several risk factors with abdominal aortic aneurysm (AAA). However, the role of ANGPTL8 in AAA pathogenesis has never been investigated. Here, we investigated the effect of ANGPTL8 knockout on AAA in ApoE-/- mice. ApoE-/-ANGPTL8-/- mice were generated by crossing ANGPTL8-/- and ApoE-/- mice. AAA was induced in ApoE-/- using perfusion of angiotensin II (AngII). ANGPTL8 was significantly up-regulated in AAA tissues of human and experimental mice. Knockout of ANGPTL8 significantly reduced AngII-induced AAA formation, elastin breaks, aortic inflammatory cytokines, matrix metalloproteinase expression, and smooth muscle cell apoptosis in ApoE-/- mice. Similarly, ANGPTL8 sh-RNA significantly reduced AngII-induced AAA formation in ApoE-/- mice. ANGPTL8 deficiency inhibited AAA formation, and ANGPTL8 may therefore be a potential therapeutic target for AAA.
Topics: Humans; Mice; Animals; Angiopoietin-Like Protein 8; Mice, Knockout, ApoE; Aortic Aneurysm, Abdominal; Aorta; Apolipoproteins E; Angiotensin II; Mice, Knockout; Disease Models, Animal; Mice, Inbred C57BL; Aorta, Abdominal; Peptide Hormones
PubMed: 37294581
DOI: 10.1042/CS20230031 -
Biomedicines Dec 2023Aortic aneurysms are responsible for significant morbidity and mortality. Despite their clinical significance, there remain critical knowledge gaps in the pathogenesis... (Review)
Review
Aortic aneurysms are responsible for significant morbidity and mortality. Despite their clinical significance, there remain critical knowledge gaps in the pathogenesis of aneurysm disease and the mechanisms involved in aortic rupture. Recent studies have drawn attention to the role of reactive oxygen species (ROS) and their down-stream effectors in chronic cardiovascular diseases and specifically in the pathogenesis of aortic aneurysm formation. This review will discuss current mechanisms of ROS in mediating aortic aneurysms, the failure of endogenous antioxidant systems in chronic vascular diseases, and their relation to the development of aortic aneurysms.
PubMed: 38275364
DOI: 10.3390/biomedicines12010003 -
Clinical Science (London, England :... Oct 2023Abdominal aortic aneurysm (AAA) is characterized by at least 1.5-fold enlargement of the infrarenal aorta, a ruptured AAA is life-threatening. Colchicine is a medicine...
Abdominal aortic aneurysm (AAA) is characterized by at least 1.5-fold enlargement of the infrarenal aorta, a ruptured AAA is life-threatening. Colchicine is a medicine used to treat gout and familial Mediterranean fever, and recently, it was approved to reduce the risk of cardiovascular events in adult patients with established atherosclerotic disease. With an AAA mice model created by treatment with porcine pancreatic elastase (PPE) and β-aminopropionitrile (BAPN), this work was designed to explore whether colchicine could protect against the development of AAA. Here, we showed that colchicine could limit AAA formation, as evidenced by the decreased total aortic weight per body weight, AAA incidence, maximal abdominal aortic diameter and collagen deposition. We also found that colchicine could prevent the phenotypic switching of vascular smooth muscle cells from a contractile to synthetic state during AAA. In addition, it was demonstrated that colchicine was able to reduce vascular inflammation, oxidative stress, cell pyroptosis and immune cells infiltration to the aortic wall in the AAA mice model. Finally, it was proved that the protective action of colchicine against AAA formation was mainly mediated by preventing immune cells infiltration to the aortic wall. In summary, our findings demonstrated that colchicine could protect against the development of experimental AAA, providing a potential therapeutic strategy for AAA intervention in the clinic.
Topics: Humans; Mice; Swine; Animals; Colchicine; Aortic Aneurysm, Abdominal; Aorta, Abdominal; Disease Models, Animal; Oxidative Stress; Mice, Inbred C57BL
PubMed: 37748024
DOI: 10.1042/CS20230499 -
Medicine Dec 2023Connective tissue disorders, including Marfan syndrome (MS) and Ehlers-Danlos syndrome (EDS), are characterized by genetic mutations affecting connective tissue... (Review)
Review
Connective tissue disorders, including Marfan syndrome (MS) and Ehlers-Danlos syndrome (EDS), are characterized by genetic mutations affecting connective tissue structural integrity. These disorders significantly elevate the risk of aortic dissection, a life-threatening condition. This comprehensive review delves into the intricate interplay between connective tissue disorders and aortic dissection, shedding light on the clinical features, pathophysiology, genetic underpinnings, diagnostic approaches, clinical management, associated comorbidities, and prognosis, mainly focusing on MS and EDS, while also exploring rare connective tissue disorders and forms of cutis laxa contributing to aortic pathology.
Topics: Humans; Connective Tissue Diseases; Marfan Syndrome; Ehlers-Danlos Syndrome; Aortic Aneurysm; Aortic Dissection; Connective Tissue
PubMed: 38050214
DOI: 10.1097/MD.0000000000036499 -
The Journal of Thoracic and... Dec 2023Thoracic aortic aneurysm and dissection has a genetic predisposition and a variety of clinical manifestations. This study aimed to investigate the clinical and molecular...
OBJECTIVES
Thoracic aortic aneurysm and dissection has a genetic predisposition and a variety of clinical manifestations. This study aimed to investigate the clinical and molecular characterizations of patients with thoracic aortic aneurysm and dissection and further explore the relationship between the genotype and phenotype, as well as their postoperative outcomes.
METHODS
A total of 1095 individuals with thoracic aortic aneurysm and dissection admitted to our hospital between 2013 and 2022 were included. Next-generation sequencing and multiplex ligation-dependent probe amplification were performed, and mosaicism analysis was additionally implemented to identify the genetic causes.
RESULTS
A total of 376 causative variants were identified in 83.5% of patients with syndromic thoracic aortic aneurysm and dissection and 18.7% of patients with nonsyndromic thoracic aortic aneurysm and dissection, including 8 copy number variations and 2 mosaic variants. Patients in the "pathogenic" and "variant of uncertain significance" groups had younger ages of aortic events and higher aortic reintervention risks compared with genetically negative cases. In addition, patients with FBN1 haploinsufficiency variants had shorter reintervention-free survival than those with FBN1 dominant negative variants.
CONCLUSIONS
Our data expanded the genetic spectrum of heritable thoracic aortic aneurysm and dissection and indicated that copy number variations and mosaic variants contributed to a small proportion of the disease-causing alterations. Moreover, positive genetic results might have a possible predictive value for aortic event severity and postoperative risk stratification.
Topics: Humans; Aortic Dissection; DNA Copy Number Variations; Aortic Aneurysm, Thoracic; Genetic Predisposition to Disease; Aorta
PubMed: 36517271
DOI: 10.1016/j.jtcvs.2022.11.004 -
Cardiovascular Diabetology May 2024In observational and experimental studies, diabetes has been reported as a protective factor for aortic dissection. 3-Hydroxybutyrate, a key constituent of ketone...
BACKGROUND
In observational and experimental studies, diabetes has been reported as a protective factor for aortic dissection. 3-Hydroxybutyrate, a key constituent of ketone bodies, has been found to favor improvements in cardiovascular disease. However, whether the protective effect of diabetes on aortic dissection is mediated by 3-hydroxybutyrate is unclear. We aimed to investigate the causal effects of diabetes on the risk of aortic dissection and the mediating role of 3-hydroxybutyrate in them through two-step Mendelian randomization.
MATERIALS AND METHODS
We performed a two-step Mendelian randomization to investigate the causal connections between diabetes, 3-hydroxybutyrate, and aortic dissection and calculate the mediating effect of 3-hydroxybutyrate. Publicly accessible data for Type 1 diabetes, Type 2 diabetes, dissection of aorta and 3-hydroxybutyrate were obtained from genome-wide association studies. The association between Type 1 diabetes and dissection of aorta, the association between Type 2 diabetes and dissection of aorta, and mediation effect of 3-hydroxybutyrate were carried out separately.
RESULTS
The IVW method showed that Type 1 diabetes was negatively associated with the risk of aortic dissection (OR 0.912, 95% CI 0.836-0.995), The weighted median, simple mode and weighted mode method showed consistent results. The mediated proportion of 3-hydroxybutyrate on the relationship between Type 1 diabetes and dissection of aorta was 24.80% (95% CI 5.12-44.47%). The IVW method showed that Type 2 diabetes was negatively associated with the risk of aortic dissection (OR 0.763, 95% CI 0.607-0.960), The weighted median, simple mode and weighted mode method showed consistent results. 3-Hydroxybutyrate does not have causal mediation effect on the relationship between Type 2 diabetes and dissection of aorta.
CONCLUSION
Mendelian randomization study revealed diabetes as a protective factor for dissection of aorta. The protective effect of type 1 diabetes on aortic dissection was partially mediated by 3-hydroxybutyrate, but type 2 diabetes was not 3-hydroxybutyrate mediated.
Topics: Mendelian Randomization Analysis; Humans; Aortic Dissection; 3-Hydroxybutyric Acid; Diabetes Mellitus, Type 2; Risk Factors; Aortic Aneurysm; Diabetes Mellitus, Type 1; Genome-Wide Association Study; Risk Assessment; Genetic Predisposition to Disease; Protective Factors; Phenotype; Biomarkers; Mediation Analysis
PubMed: 38715052
DOI: 10.1186/s12933-024-02266-3 -
International Journal of Molecular... Jul 2023Thoracic aortic aneurysm and dissection (TAAD) are complex disease states with high morbidity and mortality that pose significant challenges to early diagnosis. Patients... (Review)
Review
Thoracic aortic aneurysm and dissection (TAAD) are complex disease states with high morbidity and mortality that pose significant challenges to early diagnosis. Patients with an aneurysm are asymptomatic and typically present to the emergency department only after the development of a dissection. The extracellular matrix (ECM) plays a crucial role in regulating the aortic structure and function. The histopathologic hallmark termed medial degeneration is characterised by smooth muscle cell (SMC) loss, the degradation of elastic and collagen fibres and proteoglycan (PG) accumulation. Covalently attached to the protein core of PGs are a number of glycosaminoglycan chains, negatively charged molecules that provide flexibility, compressibility, and viscoelasticity to the aorta. PG pooling in the media can produce discontinuities in the aortic wall leading to increased local stress. The accumulation of PGs is likely due to an imbalance between their synthesis by SMCs and decreased proteolysis by A Disintegrin-like and Metalloproteinase with Thrombospondin motifs (ADAMTS) proteoglycanases in the ECM. Mouse models of TAAD indicated that these proteases exert a crucial, albeit complex and not fully elucidated, role in this disease. This has led to a mounting interest in utilising ADAMTS proteoglycanases as biomarkers of TAAD. In this review, we discuss the role of ADAMTSs in thoracic aortic disease and their potential use in facilitating the clinical diagnosis of TAAD and disease progression.
Topics: Mice; Animals; Aortic Aneurysm, Thoracic; Aorta; Aortic Dissection; Proteoglycans; Aorta, Thoracic
PubMed: 37569511
DOI: 10.3390/ijms241512135 -
International Journal of Molecular... Jul 2023Redox stress is involved in the aortic aneurysm pathogenesis in Marfan syndrome (MFS). We recently reported that allopurinol, a xanthine oxidoreductase inhibitor,...
Redox stress is involved in the aortic aneurysm pathogenesis in Marfan syndrome (MFS). We recently reported that allopurinol, a xanthine oxidoreductase inhibitor, blocked aortopathy in a MFS mouse model acting as an antioxidant without altering uric acid (UA) plasma levels. Hyperuricaemia is ambiguously associated with cardiovascular injuries as UA, having antioxidant or pro-oxidant properties depending on the concentration and accumulation site. We aimed to evaluate whether hyperuricaemia causes harm or relief in MFS aortopathy pathogenesis. Two-month-old male wild-type (WT) and MFS mice () were injected intraperitoneally for several weeks with potassium oxonate (PO), an inhibitor of uricase (an enzyme that catabolises UA to allantoin). Plasma UA and allantoin levels were measured via several techniques, aortic root diameter and cardiac parameters by ultrasonography, aortic wall structure by histopathology, and pNRF2 and 3-NT levels by immunofluorescence. PO induced a significant increase in UA in blood plasma both in WT and MFS mice, reaching a peak at three and four months of age but decaying at six months. Hyperuricaemic MFS mice showed no change in the characteristic aortic aneurysm progression or aortic wall disarray evidenced by large elastic laminae ruptures. There were no changes in cardiac parameters or the redox stress-induced nuclear translocation of pNRF2 in the aortic tunica media. Altogether, the results suggest that hyperuricaemia interferes neither with aortopathy nor cardiopathy in MFS mice.
Topics: Mice; Male; Animals; Marfan Syndrome; Antioxidants; Disease Models, Animal; Allantoin; Hyperuricemia; Aortic Aneurysm
PubMed: 37511051
DOI: 10.3390/ijms241411293 -
International Journal of Cardiology Oct 2023Hemodynamic shear stress is one of the major factors that are involved in the pathogenesis of many cardiovascular diseases including atherosclerosis and abdominal aortic... (Review)
Review
Hemodynamic shear stress is one of the major factors that are involved in the pathogenesis of many cardiovascular diseases including atherosclerosis and abdominal aortic aneurysm (AAA), through its modulatory effect on the endothelial cell's redox homeostasis and mechanosensitive gene expression. Among important mechanisms, oxidative stress, endoplasmic reticulum stress activation, and the subsequent endothelial dysfunction are attributed to disturbed blood flow and low shear stress in the vascular curvature and bifurcations which are considered atheroprone regions and aneurysm occurrence spots. Many pathways were shown to be involved in AAA progression. Of particular interest from recent findings is, the (Nrf2)/Keap-1 pathway, where Nrf2 is a transcription factor that has antioxidant properties and is strongly associated with several CVDs, yet, the exact mechanism by which Nrf2 alleviates CVDs still to be elucidated. Nrf2 expression is closely affected by shear stress and was shown to participate in AAA. In the current review paper, we discussed the link between disturbed hemodynamics and its effect on Nrf2 as a mechanosensitive gene and its role in the development of endothelial dysfunction which is linked to the progression of AAA.
Topics: Humans; NF-E2-Related Factor 2; Oxidative Stress; Atherosclerosis; Hemodynamics; Aortic Aneurysm, Abdominal; Stress, Mechanical
PubMed: 37536420
DOI: 10.1016/j.ijcard.2023.131238