Advances and challenges in regenerative therapies for abdominal aortic aneurysm

Frontiers in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 11

Published: June 4, 2024

Abdominal aortic aneurysm (AAA) is a significant source of mortality worldwide and carries greater than 80% after rupture. Despite extensive efforts to develop pharmacological treatments, there currently no effective agent prevent growth Current treatment paradigms only rely on the identification surveillance small aneurysms, prior ultimate open surgical or endovascular repair. Recently, regenerative therapies have emerged as promising avenues address degenerative changes observed in AAA. This review briefly outlines current clinical management principles, characteristics, pharmaceutical targets Subsequently, thorough discussion approaches provided. These include cellular (vascular smooth muscle cells, endothelial mesenchymal stem cells) well delivery therapeutic molecules, gene therapies, biomaterials. Lastly, additional barriers considerations for translation are In conclusion, hold promise situ reversal tissue damages AAA, necessitating sustained research innovation achieve successful translatable new era AAA management.

Language: Английский

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Unraveling the Complexity of Abdominal Aortic Aneurysm: Multiplexed Imaging Insights into C-Reactive Protein-Related Variations

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 26, 2024

ABSTRACT Background Abdominal aortic aneurysm (AAA) is a potentially lethal condition that often remains asymptomatic until it ruptures. Recent research suggests immune-inflammatory processes are associated with AAA development, yet the exact mechanisms remain unclear. Serum C-reactive protein (CRP) serves as prognostic marker for and various cardiovascular diseases. When CRP accumulates in damaged tissues, transforms into monomeric form, exacerbating tissue damage. Our previous study confirmed presence of deposition eroded atherosclerosis regions, accompanied by an increased infiltration inflammatory cells. However, comprehensive understanding specific changes cellular landscape attributable to lacking. Here, we aimed explore cellular-level alterations AAAs varying levels. Methods We categorized patients High-CRP (≥0.1 mg/dL, ≥3+ IHC score, n=6) Low-CRP (≤0.1 ≤1+ n=3), used normal aorta specimens baseline control. The immune stromal components was characterized using Co-Detection Indexing (CODEX) imaging 31 DNA-barcoded antibodies, followed single-cell-based analysis GPU-accelerated unsupervised clustering. Results identified 51 distinct cell types cohort revealed significant differences expression patterns among groups. In AAA, cells decreased significantly, while proportions sharply increased. Lag3+ T regulators decreased, leading increase CD3+ composition within atherosclerotic plaques degree AAA. group showed M1 Ki67+ proliferating macrophages, exhibited intensified fibrosis M2 macrophages. Conclusions found variations distribution walls based on These findings suggest potential link between CRP-related progression. HIGHLIGHTS By performing CODEX (co-detection indexing) multiplexed paraffin-embedded, formalin-fixed archived abdominal samples levels, segmented 415,365 clusters. led spatial relationships, distances, enrichment cells.. AAA-High CRP, there macrophages observed plaque. AAA-Low severe results plaque alters immune-stromal

Language: Английский

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The pleiotropic effects of statins inrheumatoid arthritis

Journal of Pharmacy and Pharmacology, Journal Year: 2023, Volume and Issue: 75(7), P. 910 - 920

Published: April 7, 2023

Abstract Objectives Rheumatoid arthritis (RA) is an inflammatory and autoimmune disease. Studies over the past two decades suggest that statins have a beneficial impact on complications associated with RA. These include RA disease activity risk for cardiovascular diseases (CVD). This review aims to discuss efficacy of statin therapy in Key findings The current evidence suggests statins' immunomodulatory antioxidant properties significantly reduce response patients In patients, CVD reduced by treatment, discontinuation increased risk. Summary combined effect improving vascular function, lowering lipid levels, reducing inflammation responsible decreased all-cause mortality users. Further clinical studies are needed ensure therapeutic

Language: Английский

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Exploration of small molecule compounds targeting abdominal aortic aneurysm based on CMap database and molecular dynamics simulation

Vascular, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 18, 2024

The mitigation of abdominal aortic aneurysm (AAA) growth through pharmaceutical intervention offers the potential to avert perils associated with AAA rupture and subsequent need for surgical intervention. Nevertheless, existing effective drugs treatment are limited, necessitating a pressing exploration novel therapeutic medications.

Language: Английский

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Aneurisma de aorta abdominal: uma revisão sistemática sobre a prevalência, diagnóstico e estratégias de tratamento

Brazilian Journal of Health Review, Journal Year: 2024, Volume and Issue: 7(4), P. e72108 - e72108

Published: Aug. 22, 2024

O aneurisma de aorta abdominal (AAA) é uma dilatação significativa da aorta, geralmente localizada na parte infrarrenal, afetando aproximadamente 5% população, com variação entre sexos e idades. Predominantemente assintomático, o AAA frequentemente descoberto incidentalmente através exames imagem, embora sua ruptura seja das principais causas mortalidade, principalmente devido ao aumento pressão intraluminal enfraquecimento parede aórtica. A prevalência do subestimada à apresentação assintomática variações epidemiológicas, fatores risco como idade avançada, tabagismo hipertensão arterial sendo fortemente associados. fisiopatologia envolve estresse oxidativo, inflamação crônica degeneração matriz extracelular, resultando em aórtica formação aneurismas. diagnóstico precoce crucial feito ultrassonografia, tomografia computadorizada ou ressonância magnética, cada método oferecendo vantagens limitações específicas. tratamento guiado pelo diâmetro ruptura, opções que variam monitoramento vigilante para aneurismas menores a intervenções cirúrgicas, reparo endovascular aberto, maiores rápido crescimento. Assim, continua ser condição desafiadora, importantes avanços no tratamento, prometem melhorar os desfechos pacientes. incorporação novas tecnologias técnicas rastreamento pode oferecer perspectivas promissoras detecção gestão eficaz doença. Futuros estudos inovações são essenciais aprimorar as estratégias prevenção intervenção, maximizando qualidade vida reduzindo mortalidade associada AAA.

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Causal Relationships between Lipid-Lowering Drug Target and Aortic Disease and Calcific Aortic Valve Stenosis: A Two-Sample Mendelian Randomization

Reviews in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 25(8)

Published: Aug. 19, 2024

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), cholesteryl ester transfer protein (CETP) and apolipoprotein C3 (APOC3) are pivotal regulators of lipid metabolism, with licensed drugs targeting these genes. The use lipid-lowering therapy via the inhibition genes has demonstrated a reduction in risk cardiovascular disease. However, concerns persist regarding their potential long-term impact on aortic diseases calcific valve disease (CAVS). This study aims to investigate causal relationships between genetic variants resembling disease, as well using Mendelian randomization (MR). Methods: We conducted drug-target employing summary-level statistics low-density lipoprotein cholesterol (LDL-C) proxy loss-of-function PCSK9, HMGCR, CETP APOC3. Subsequently, we investigated association stenosis diseases, including thoracic aneurysm (TAA), abdominal (AAA), dissection (AD). Results: genetically constructed mimicking lower LDL-C levels were associated decreased coronary artery validating reliability. Notably, HMGCR exhibited robust protective effect against TAA (odds ratio (OR): 0.556, 95% CI: 0.372–0.831, p = 0.004), AAA (OR: 0.202, 0.107–0.315, 4.84 × 10-15), AD 0.217, 0.098–0.480, 0.0002). Similarly, APOC3 proxies reduced 0.595, 0.485–0.730, 6.75 10-7, OR: 0.127, 0.066–0.243, 4.42 10-10, 0.387, 0.182–0.824, 0.014, respectively) while showing neutral AD. Inhibition showed promising preventing CAVS odds ratios 0.554 0.554, 0.433–0.707, 2.27 10-6), 0.717 (95% 0.635–0.810, 9.28 10-8), 0.540 0.351–0.829, 0.005), respectively. did not demonstrate any significant benefits 0.704–1.544, 0.836). consistency findings across various methods, accounting for different assumptions concerning pleiotropy, enhances inference. Conclusions: Our MR analysis reveals that statin administration AAA, TAA, CAVS. PCSK9 inhibitors but have positive exhibit impact, primarily no discernible extending or

Language: Английский

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A dual-action Rhein-peptide hydrogel synergistically inhibits inflammation and matrix degradation for therapeutic mitigation of abdominal aortic aneurysm

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: unknown, P. 155723 - 155723

Published: Sept. 1, 2024

Language: Английский

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Different Proteins as Biomarkers for Sac Shrinkage After Endovascular Aortic Repair of Abdominal Aortic Aneurysms

Journal of Cardiovascular Development and Disease, Journal Year: 2024, Volume and Issue: 11(11), P. 374 - 374

Published: Nov. 20, 2024

This study aims to identify circulating biomarkers by using proteomic analysis associated with sac shrinkage or expansion in patients undergoing endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAAs).

Language: Английский

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Effective Hydrogel Vascular Patch Dual‐Loaded with Cycloastragenol Nanostructured Lipid Carriers and Doxycycline for Repairing Extravascular Injury in Abdominal Aortic Aneurysm

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Endovascular aneurysm repair (EVAR) plays a crucial role in the treatment of abdominal aortic (AAA) clinic, but remains patient's body after surgery, continuing to pose risk progression. Cycloastragenol (CAG) is proven be an effective anti-AAA drug, and its vascular protective effects can further improved when hydrophobic CAG encapsulated into nano-sized formulations enhance bioavailability. In this context, study developed extravascular patch hydrogel loaded with nanostructured lipid carriers hydrophilic drug doxycycline hydrochloride (DOX). The delivered onto mouse aortas promote local permeation hydrophilic/hydrophobic drugs at vessel sites provide protection against AAA injury induced by elastase. This introduces novel promising approach for treatment, which serve as supplementary strategy EVAR surgery.

Language: Английский

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Salivary cortisol as a biomarker of stress in surgical patients

Journal of Medical Biochemistry, Journal Year: 2023, Volume and Issue: 42(3), P. 469 - 475

Published: Jan. 1, 2023

Surgical stress and pain result in activation of hypothalamus-pituitary-adrenal axis. The aim this study was to establish the effects postoperative various modalities analgesic administration on salivary serum cortisol levels, as well validity a indicator surgical patients.A randomized controlled trial involved 60 patients scheduled for elective abdominal aortic aneurysm surgery. Patients were randomly divided into two groups depending model analgesia. first group (MI - morphine intermittently) included given doses 0.1 mg/kg/6h s.c. intermittently. second (MPCA patient-controlled analgesia) who received via PCA system intravenous adjusted dose 1 mg per shot lockout interval 6 minutes.Hirurški stres i bol su uzrok aktivacije hipotalamusno-hipofizno-nadbubrežne osovine. Cilj ove studije bio je da se utvrdi uticaj postoperativnog bola različitih vidova administracije analgetika na vrednosti kortizola u serumu salivi, kao li salivarni kortizol dobar pokazatelj stresa kod hirurških pacijenata.Randomizovana kontrolisana studija koja uključila pacijenata primljenih za elektivnu operaciju aneurizme abdominalne aorte. Pacijenti metodom slučajnog izbora podeljeni dve grupe zavisnosti od modela postoperativne analgezije. Prvu grupu intermitentna primena morfina) činili pacijenti koji dobijali morfin intermitentno dozi U drugoj grupi analgezija morfinom strane pacijenta) bili takozvanom intravenska morfina pritisak/1 mg, minuta.Intenzitet nije značajno razlikovao do desetog sata nakon operacije. Međutim, periodu osamnaestog operacije izraženiji MPCA (P < 0.05). Hemodinamska nestabilnost bila zastupljenija MI (40.0% vs 6.7%, P = 0.0048). Serumski gotovo identičan po grupama 509.4 nmol/L 511.0 nmol/L, 0.1473). Salivarni viši ali lika statistički značajna (47.1 116.3 0.0970).Naša pokazala senzitivniji biomarker odnosu serumski kortizol.

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