Inhibition of ATP-citrate lyase by bempedoic acid protects against abdominal aortic aneurysm formation in mice

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 184, P. 117876 - 117876

Published: Jan. 30, 2025

Language: Английский

---

Atractylenolide-I prevents abdominal aortic aneurysm formation through inhibiting inflammation

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 31, 2025

Abdominal aortic aneurysm (AAA) is a degenerative disease with high mortality. Chronic inflammation plays vital role in the formation of AAA. Atractylenolide-I (ATL-I) major bioactive component Rhizoma Atractylodis Macrocephalae that exerts anti-inflammatory effects various diseases. The purpose this study to investigate ATL-I progression AAA was constructed C57BL/6 mice by porcine pancreatic elastase (PPE)-incubation, and diameter aorta measured ultrasound. administered gavage on second day after modeling explore its significance pathological molecular alteration investigated immunostaining, ELISA, qRT-PCR Western blotting. inhibited dilatation abdominal decreased incidence alleviated infiltration macrophages adventitia reduced levels proinflammatory factor IL-1β IL-6 circulatory system, while increasing expression IL-10. Moreover, restrained loss smooth muscle cells elastic fiber degradation suppressing MMP-2 MMP-9 expression. Mechanistically, phospho-AMPK elevated groups, administration suppressed improve damage aorta. meliorated vascular targeting AMPK signaling, ultimately inhibiting formation, which provided an alternative agent for treatment.

Language: Английский

---

Angiotensin Dysregulation in Patients with Arterial Aneurysms

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1502 - 1502

Published: Feb. 11, 2025

Besides playing a critical role in maintaining cardiovascular homeostasis, the renin–angiotensin–aldosterone system (RAS) has been strongly implicated (aortic) aneurysm pathogenesis. This study aims to investigate systemic and local levels of angiotensin (Ang) its metabolites patients with arterial aneurysms, predominantly abdominal aortic using advanced biochemical profiling techniques provide new insights into involvement RAS genesis. A prospective, single-center was conducted between October 2023 July 2024. Serum Ang metabolite were measured Fingerprint technology. Aortic tissue samples analyzed for activity, including enzyme activity. Additionally, pre- postoperative serum obtained select group patients. In total, 37 56 controls included. Aneurysm exhibited higher nearly all compared controls, significant differences I (p = 0.002), II 0.047), 1–5 0.004), Renin 0.014) without pharmacological interference. receiving ACE inhibitors showed lower concentrations ACE2 activity 0.042) increased IV 0.049) controls. Postoperative measurements indicated different dynamics regarding changes or inhibition. provides first comprehensive characterization profiles These findings add body evidence associations pathogenesis aneurysms.

Language: Английский

---

Efficacy and safety of endovascular repair versus open surgery for ruptured abdominal aortic aneurysm: a comparative study

American Journal of Cancer Research, Journal Year: 2025, Volume and Issue: 15(3), P. 1234 - 1247

Published: Jan. 1, 2025

Ruptured abdominal aortic aneurysm (rAAA) is a life-threatening condition with high mortality. This study compared the efficacy and safety of open surgical repair (OSR) endovascular (EVAR) in treatment rAAA. A retrospective analysis clinical data was conducted for 232 rAAA patients treated at Taizhou Central Hospital First Affiliated Wenzhou Medical College. Patients were divided into two groups based on methods: OSR group (n=84) EVAR (n=148). Perioperative indicators, perioperative complication rates, 1-year mortality rates compared. further survival (n=160) death (n=72) their status, risk factors affecting prognosis analyzed. Postoperative pain evaluated using Visual Analog Scale (VAS), Verbal Rating (VRS), Present Pain Intensity (PPI). Serum levels C-reactive protein (CRP) white blood cells (WBC), pro-inflammatory interleukins (IL-1α, IL-6, IL-8), tumor necrosis factor-α (TNF-α) measured before after enzyme-linked immunosorbent assays (ELISA). Compared group, had significantly shorter time, less intraoperative bleeding (IOB) transfusion volume, reduced infusion fasting first walk ICU hospital days. The incidence complications lower than that (P<0.05). scores (VAS, VRS, PPI) serum CRP, WBC, IL-1α, IL-8, TNF-α those (all P<0.05). There no significant difference between (28.95% vs. 11.80%, P>0.05). However, rate (38.1% 27.0%, Multivariate logistic regression identified Alb<40 g/L (P=0.004), Cre≥1.5 mg/dL (P=0.007), urea nitrogen ≥25 (P=0.001), ALT≥40 U/L (P=0.002), method (P=0.024) as independent poor postoperative prognosis. demonstrates advantages over reducing trauma, decreasing complications, alleviating inflammatory responses, improving rates.

Language: Английский

---

The Molecular Mechanisms of Bergapten Against Abdominal Aortic Aneurysm: Evidence From Network Pharmacology, Molecular Docking/Dynamics, and Experimental Validation

Journal of Cellular Biochemistry, Journal Year: 2025, Volume and Issue: 126(4)

Published: March 30, 2025

ABSTRACT This study endeavors to assess the potential protective role of bergapten (BP) in mitigating abdominal aortic aneurysm (AAA) and decipher underlying mechanisms molecular targets. Network pharmacology was utilized search for targets BP against AAA. Molecular docking dynamics simulations were validate interaction with core targets, then therapeutic effect mechanism on AAA verified by using an elastase‐induced model. analysis identified five pharmacological BP, including EGFR, SRC, PIK3CA, PIK3CB, JAK2. further prioritized JAK2 as most promising candidate treatment The results animal experiments demonstrated that significantly reduced expression inflammatory cytokines IL‐6, TNF‐α, IL‐1β tissue mouse model, inhibited phosphorylation STAT3. plays important AAA, it may become a drug combat progression. inhibitory vascular progression attenuation cell infiltration be related regulation JAK2/STAT3 signaling pathway.

Language: Английский

---

Role of Inflammatory and Proresolving Mediators in Endothelial Dysfunction

Basic & Clinical Pharmacology & Toxicology, Journal Year: 2025, Volume and Issue: 136(5)

Published: March 31, 2025

ABSTRACT Excessive local inflammation is a common mechanism in many cardiovascular diseases (CVDs) such as hypertension, atherosclerosis and aortic aneurysms. In endothelial cells, inflammatory cytokines interferons, tumour necrosis factor alpha or interleukins increase oxidative stress contractile prostanoids the expression of adhesion molecules that reduce nitric oxide (NO) availability bind leucocytes, thereby impairing function. Despite this evidence, anti‐inflammatory therapies are not yet indicated for treatment most CVD. Resolution mediated by family specialized pro‐resolving mediators (SPMs) act on cognate G protein–coupled receptors to limit immune cell infiltration initiate tissue repair. SPMs, generated from omega‐3 omega‐6 polyunsaturated fatty acids, belong four major families: lipoxins, resolvins, protectins maresins. SPM expressed vascular cells where they regulate important processes phagocytosis polarization, production cytokines, NO prostacyclin, modulation smooth muscle phenotype. Growing evidence animal models demonstrates activation can protect function structure provide beneficial effects various We will review recent advances role SPMs (dys)function atherosclerosis,

Language: Английский

---

Identification of Diagnostic Biomarkers and Therapeutic Targets for Abdominal Aortic Aneurysms Based on Disulfidptosis Mechanism

Current Pharmaceutical Analysis, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

---

Colchicine protects against the development of experimental abdominal aortic aneurysm

Clinical Science, Journal Year: 2023, Volume and Issue: 137(19), P. 1533 - 1545

Published: Sept. 25, 2023

Abdominal aortic aneurysm (AAA) is characterized by at least 1.5-fold enlargement of the infrarenal aorta, a ruptured AAA life-threatening. Colchicine medicine used to treat gout and familial Mediterranean fever, recently, it was approved reduce risk cardiovascular events in adult patients with established atherosclerotic disease. With an mice model created treatment porcine pancreatic elastase (PPE) β-aminopropionitrile (BAPN), this work designed explore whether colchicine could protect against development AAA. Here, we showed that limit formation, as evidenced decreased total weight per body weight, incidence, maximal abdominal diameter collagen deposition. We also found prevent phenotypic switching vascular smooth muscle cells from contractile synthetic state during In addition, demonstrated able inflammation, oxidative stress, cell pyroptosis immune infiltration wall model. Finally, proved protective action formation mainly mediated preventing wall. summary, our findings experimental AAA, providing potential therapeutic strategy for intervention clinic.

Language: Английский

---

P4HA3 Promotes Head and Neck Squamous Cell Carcinoma Progression via the WNT/β-Catenin Signaling Pathway

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 260, P. 155481 - 155481

Published: July 22, 2024

Language: Английский

---

PDE4 Phosphodiesterases in Cardiovascular Diseases: Key Pathophysiological Players and Potential Therapeutic Targets

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(23), P. 17017 - 17017

Published: Nov. 30, 2023

3′,5′-cyclic adenosine monophosphate (cAMP) is a second messenger critically involved in the control of myriad processes with significant implications for vascular and cardiac cell function. The temporal spatial compartmentalization cAMP governed by activity phosphodiesterases (PDEs), superfamily enzymes responsible hydrolysis cyclic nucleotides. Through fine-tuning signaling, PDE4 could play an important role hypertrophy arrhythmogenesis, while it decisively influences homeostasis through smooth muscle proliferation, migration, differentiation contraction, as well regulating endothelial permeability, angiogenesis, monocyte/macrophage activation cardiomyocyte This review summarizes current knowledge recent advances understanding contribution subfamily to cardiovascular function underscores intricate challenges associated targeting therapeutic strategy management diseases.

Language: Английский

---