Homocysteine-Enhanced Proteolytic and Fibrinolytic Processes in Thin Intraluminal Thrombus and Adjacent Wall of Abdominal Aortic Aneurysm: Study In Vitro
| Autor: | Kornel Chełstowski, Maria Jastrzębska, Jeremy Clark, Miłosław Cnotliwy, Marta Zuchowski, Aldona Siennicka |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Homocysteine Article Subject medicine.medical_treatment lcsh:Medicine 030204 cardiovascular system & hematology General Biochemistry Genetics and Molecular Biology Thromboplastin Pathogenesis 03 medical and health sciences Aortic aneurysm chemistry.chemical_compound 0302 clinical medicine Aneurysm Internal medicine Fibrinolysis medicine Humans Thrombus Aged Aged 80 and over General Immunology and Microbiology Chemistry lcsh:R Plasminogen Thrombosis General Medicine Middle Aged medicine.disease Abdominal aortic aneurysm 030104 developmental biology Endocrinology Coagulation Tissue Plasminogen Activator Proteolysis Matrix Metalloproteinase 2 Female Aortic Aneurysm Abdominal Research Article |
| Zdroj: | BioMed Research International BioMed Research International, Vol 2018 (2018) |
| ISSN: | 2314-6141 |
| Popis: | Homocysteine (Hcy) may affect the pathogenesis of abdominal aortic aneurysms (AAAs) through enhancement of proteolysis and an impaired coagulation/fibrinolysis system. Intensified haemostatic capacity may promote local proteolytic degradation of the aortic wall. This study aimed to examine the effects of Hcy on haemostatic and proteolytic processes in samples of thick and thin fragments of the ILT and underlying walls.Subjects and Methods. Thirty-six patients who underwent AAA surgery were enrolled. Aneurysm tissue sections were incubated with DL-Hcy (100 and 500μmol/L) in a series of experiments and analyzed for concentration/activity of proteolytic and haemostatic markers by enzyme-linked immunosorbent assay.Results. Incubation of wall underlying thin ILT segments (B) with DL-Hcy resulted in an increase of active MMP-2 levels compared to control tissue (9.54 ± 5.88 versus 7.44 ± 4.48, p=0.011). DL-Hcy also induced t-PA and plasminogen concentration increases in thin thrombus sections (B1) compared to control tissue (respectively: 1.39 ± 1.65 versus 0.84 ± 0.74, p=0.024; 11.64 ± 5.05 versus 10.34 ± 5.52, p=0.018). In contrast, wall adjacent to thick thrombus segments (A) showed decreases in MMP-2 and TF activities compared to control (respectively, 5.89 ± 3.39 versus 7.26 ± 5.49, p=0.046; 67.13 ± 72.59 versus 114.46 ± 106.29, p=0.007). In thick ILT sections (A1), DL-Hcy decreased MMP-2 activity and t-PA and plasminogen concentrations compared to control tissue (respectively, 2.53 ± 2.02 versus 3.28 ± 2.65, p=0.006; 0.67 ± 0.57 versus 0.96 ± 0.91, p=0.021; 9.25 ± 4.59 versus 12.63 ± 9.56, p=0.017). In addition, analysis revealed positive correlations at all sites between activities/concentrations of MMP-2, TF, and PAI-1 measured in control tissues and after incubation with DL-Hcy.Conclusions. These data indicate the potential for excess Hcy to enhance damage of arterial wall in thinner AAA segments as a result of the increased activity of MMP-2 and fibrinolytic factors. |
| Databáze: | OpenAIRE |
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