Animal Models, Pathogenesis, and Potential Treatment of Thoracic Aortic Aneurysm

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 901 - 901

Published: Jan. 11, 2024

Thoracic aortic aneurysm (TAA) has a prevalence of 0.16–0.34% and an incidence 7.6 per 100,000 person-years, accounting for 1–2% all deaths in Western countries. Currently, no effective pharmacological therapies have been identified to slow TAA development prevent rupture. Large TAAs are treated with open surgical repair less invasive thoracic endovascular repair, both which high perioperative mortality risk. Therefore, there is urgent medical need identify the cellular molecular mechanisms underlying rupture develop new therapies. In this review, we summarize animal models including recent developments porcine zebrafish models: can assess therapeutic devices or intervention strategies large mammal employ large-scale small-molecule suppressor screening microwells. The second part review covers current views pathogenesis, derived from studies using these models, focus on roles transforming growth factor-beta (TGFβ) pathway vascular smooth muscle cell (VSMC)-elastin-contractile unit. last discusses treatment options as they emerge preclinical studies.

Language: Английский

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Sympathetic Nervous System and Atherosclerosis

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13132 - 13132

Published: Aug. 23, 2023

Atherosclerosis is characterized by the narrowing of arterial lumen due to subendothelial lipid accumulation, with hypercholesterolemia being a major risk factor. Despite recent advances in effective lipid-lowering therapies, atherosclerosis remains leading cause mortality globally, highlighting need for additional therapeutic strategies. Accumulating evidence suggests that sympathetic nervous system plays an important role atherosclerosis. In this article, we reviewed innervation vasculature, norepinephrine synthesis and metabolism, activity measurement, common signaling pathways activation. The focus paper was review effectiveness pharmacological antagonists or agonists adrenoceptors (α1, α2, β1, β2, β3) renal denervation on All five types are present blood vessels. α1 blockers inhibit but increase heart failure while α2 agonism may protect against newer generations β β3 promising therapies atherosclerosis; however, new randomized controlled trials warranted investigate these inhibition cardiovascular reduction future. humans yet be established.

Language: Английский

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Neuroimmune Interactions and Their Role in Immune Cell Trafficking in Cardiovascular Diseases and Cancer

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2553 - 2553

Published: March 12, 2025

Sympathetic nerves innervate bone marrow and various immune organs, where norepinephrine—the primary sympathetic neurotransmitter—directly interacts with cells that express adrenergic receptors. This article reviewed the key molecular pathways triggered by activation explored how activity influences cell migration. Norepinephrine serves as a chemoattractant for monocytes, macrophages, stem cells, promoting migration of myeloid while inhibiting lymphocytes at physiological concentrations. We also examined role infiltration in cardiovascular diseases cancer. Evidence suggests increases into target tissues across diseases, including atherosclerosis, hypertension, cardiac fibrosis, hypertrophy, arrhythmia, myocardial infarction, heart failure, stroke. Conversely, may serve potential therapeutic strategy to treat these conditions reducing macrophage infiltration. Furthermore, promotes accumulation cancer tissues, mirroring its effects suppressing T lymphocyte cancerous sites. These changes contribute increased growth metastasis. Thus, could help protect against enhancing presence tumors.

Language: Английский

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Dexmedetomidine Reduces Chronic Stress–Related Thrombosis in a Mouse FeCl₃ Model

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(9)

Published: April 30, 2025

ABSTRACT Chronic psychological stress (CPS) is a significant risk factor for thrombotic cardio‐cerebrovascular diseases (TCVDs). Clinical data suggest that the α 2 ‐adrenergic receptor (AdR‐α ) agonist dexmedetomidine (Dex) can influence coagulation in stress‐exposed intensive care unit patients. Given important role of protease‐activated receptor‐2 (PAR‐2) vascular pathobiology, we aimed to investigate potential effects Dex on stress‐related thrombus formation, focusing PAR‐2 signaling pathway. Eight‐week‐old male mice underwent non‐stress and immobilization with treatment weeks were then subjected carotid artery thrombosis induction using ferric chloride (FeCl 3 ). On Day 14 post‐stress, exhibited increased weight length, along harmful alterations plasma levels von Willebrand metalloproteinase thrombospondin Type 13 motifs. Additionally, arterial protein and/or mRNA PAR‐2, p‐Akt, Bcl‐2, cleaved caspase‐3, cytochrome c , gp91 phox TNF‐α, MCP‐1, ICAM‐1, VCAM‐1, TLR‐4 altered, accompanied by endothelial loss. reversed these changes. Conversely, AdR‐α2 blockage yohimbine diminished benefits Dex. In vitro, reduced serum‐induced reactive oxygen species production apoptosis, beneficial levels. Yohimbine effects. Thus, activation appeared mitigate formation undergoing FeCl ‐induced surgery, possibly negatively regulating signaling. These findings therapeutic strategy CPS‐related events patients TCVDs.

Language: Английский

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Effect of Hydralazine on Angiotensin II-Induced Abdominal Aortic Aneurysm in Apolipoprotein E-Deficient Mice

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(21), P. 15955 - 15955

Published: Nov. 3, 2023

The rupture of an abdominal aortic aneurysm (AAA) causes about 200,000 deaths worldwide each year. However, there are currently no effective drug therapies to prevent AAA formation or, when present, decrease progression and rupture, highlighting urgent need for more research in this field. Increased vascular inflammation enhanced apoptosis smooth muscle cells (VSMCs) implicated formation. Here, we investigated whether hydralazine, which has anti-inflammatory anti-apoptotic properties, inhibited pathological hallmarks. In cultured VSMCs, hydralazine (100 μM) the increase inflammatory gene expression induced by acrolein hydrogen peroxide, two oxidants that may play a role pathogenesis. effect was associated with caspase 8 expression. mouse model subcutaneous angiotensin II infusion (1 µg/kg body weight/min) 28 days apolipoprotein E-deficient mice, treatment (24 mg/kg/day) significantly decreased incidence from 80% 20% suprarenal diameter 32% 2.26 mm 1.53 mm. Hydralazine also increased survival rate 60% 100%. conclusion, model, its properties.

Language: Английский

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Decoding vascular aging: implications for atherosclerosis progression and clinical intervention

Published: Aug. 2, 2024

Age-related pathologies, particularly cardiovascular disorders, pose a significant global health concern. The World Health Organization (WHO) predicts an increase in advanced mortality by 2030 unless critical interventions are implemented. Atherosclerosis remains the major cause of various diseases. Hence, this review focused on interaction between known mechanisms vascular aging, disease manifestation, and progression during atherosclerosis. In review, we highlighted five altered models: genomic instability, neurohormonal deregulation, epigenetics, protein regulation, gut microbiome. articles were selected from indexed scientific databases. It is important to note that equally interrelated with other aging pathways, such as inflammation senescence. conclusion, atherosclerosis multifaceted cholesterol-lowering therapy has been widely used. However, more than one specific action line required eradicate or slow down its manifestation. Equally, establishing balance stressors resulting injuries stress buffering treatment promising therapeutic targets reviewed include angiotensin (1–7)/MAS axis, microbiome, histone deacetylases, DNA repair systems, noncoding RNAs, β3/dopamine adrenoceptors, senescence checkpoints.

Language: Английский

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FSpatial metabolomics to discover hypertrophic scar relevant metabolic alterations and potential therapeutic strategies: A preliminary study

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 153, P. 107873 - 107873

Published: Oct. 5, 2024

Language: Английский

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The impact of inflammatory and oxidative stress biomarkers on the sympathetic nervous system in severe coronary atherosclerosis

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

Published: Oct. 14, 2024

Objective The present study aimed at evaluating the association between sympathetic nervous system activation (SNS) and severity of coronary artery disease (CAD). In addition, we tested hypothesis that inflammation oxidative stress influence SNS activation. Methods Adult patients with severe CAD scheduled for bypass graft (CABG) surgery were enrolled. SYNTAX I score was calculated based on angiography. Systemic estimated through circulating levels norepinephrine (NE). Plasma pro-inflammatory cytokines (IL 1β, IL 6 HIF 1α) molecules (SOD-1 LOX-1) obtained prior to surgery. Results Circulating NE significantly correlated CAD, as assessed by ( p 0.002; r 0.329). Elevated markers increased concentrations (for IL-1β: < 0.001, = 0.49; IL-6 NE: 0.003, 0.32; HIF-1α 0.049, 0.21). Additionally, associated SOD-1 0.016, 0.26; LOX-1 0.004, 0.31). Conclusion referred CABG, activation, indicated plasma levels, score, well stress. This suggests inflammation, stress, form an interconnected network, each component influencing others. It might be interest develop a scoring including identify require more aggressive approach lower modulate system. could use especially in setting intervention -such CABG

Language: Английский

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Thermal Stability and Kinetics of Degradation of Moxonidine as Pure Ingredient vs. Pharmaceutical Formulation

Processes, Journal Year: 2023, Volume and Issue: 11(6), P. 1738 - 1738

Published: June 7, 2023

The stability of active pharmaceutical ingredients (APIs) and the corresponding formulations are nowadays great importance in research technology. quality an API or finished products (FPPs) is time dependent under influence several parameters, such as light air exposure, temperature, humidity. Additionally, profile influenced by formulation composition, due to presence excipients characteristic packaging materials. In this sense, main objective study was analyze degradation kinetics antihypertensive drug moxonidine a pure ingredient (MOX) two different solid mixtures, one (MOXTAB) other enriched MOX (MOXMIX). As investigation techniques, FTIR (Fourier transform infrared) spectroscopy TG/DTG/HF analysis were employed, while thermoanalytical data processed according ASTM E698 kinetic method isoconversional methods Flynn–Wall–Ozawa (FWO) Friedman (FR). revealed that have stabilizing effect on (in terms Ea values), but decomposition mechanism samples complex, results suggested vs. α values.

Language: Английский

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Animal Models and Pathogenesis of Thoracic Aortic Aneurysm

Published: Dec. 19, 2023

Thoracic aortic aneurysm (TAA) has a prevalence of 0.16%-0.34% and an incidence 7.6 per 100,000 person-years, accounting for 1%-2% all deaths in Western countries. Currently, no effective pharmacological therapies have been identified to slow TAA development prevent rupture. Large TAAs are treated with open surgical repair less invasive thoracic endovascular repair, both which high perioperative mortality risk. Therefore, there is urgent medical need identify the cellular molecular mechanisms underlying rupture develop new therapies. In this review, we summarize animal models including recent developments porcine zebrafish models: can assess therapeutic devices or intervention strategies large mammal employ large-scale small-molecule suppressor screening microwells. The second part review covers current views pathogenesis, focus on roles transforming growth factor-beta (TGFβ) pathway vascular smooth muscle cell (VSMC)-elastin-contractile unit. last discusses treatment options as they emerge from preclinical studies.

Language: Английский

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