RESUMEN

Background and Objectives: Coronary artery disease (CAD) is the foremost cause of adult disability and mortality. There is an urgent need to focus on the research of new approaches for the prevention and treatment of CAD. Materials and Methods: The effects of peptides isolated from the blood plasma of CAD patients on endothelial cell secretion using the in vitro model have been tested. Human endothelial progenitor cells (HEPCs) were incubated for 24 h with peptides isolated from the plasma of healthy subjects or patients with stable angina, progressive unstable angina, and myocardial infarction. The contents of some soluble anticoagulant as well as procoagulant mediators in HEPC culture treated with peptide pools were then compared. Results and Conclusion: The results show that peptides from the plasma of patients with myocardial infarction promote endothelial cells to release both von Willebrand factor and endothelin-1, increasing vasoconstriction and shifting hemostatic balance toward a prothrombotic state. In contrast, peptides from the plasma of patients with progressive unstable angina suppress the secretion of endothelin-1 by HEPCs, while the secretion of both von Willebrand factor and tissue plasminogen activator was increased. As can be seen from the results obtained, disease derived peptides may contribute to the homeostasis of living organisms or the progression of pathological processes.

Asunto(s)

Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Adulto , Humanos , Activador de Tejido Plasminógeno , Enfermedad de la Arteria Coronaria/complicaciones , Factor de von Willebrand , Endotelina-1 , Células Endoteliales , Angina Inestable , Péptidos , Plasma

RESUMEN

AIM: To investigate the role of protein tyrosine phosphorylation in gastric wound formation and repair following ulceration. METHODS: Gastric lesions were induced in rats using restraint cold stress. To investigate the effect of oxidative and nitrosative cell stress on tyrosine phosphorylation during wound repair, total activity of protein tyrosine kinase (PTK), protein tyrosine phosphatase (PTP), antioxidant enzymes, nitric oxide synthase (NOS), 2',5'-oligoadenylate synthetase, hydroxyl radical and zinc levels were assayed in parallel. RESULTS: Ulcer provocation induced an immediate decrease in tyrosine kinase (40% in plasma membranes and 56% in cytosol, P < 0.05) and phosphatase activity (threefold in plasma membranes and 3.3-fold in cytosol), followed by 2.3-2.4-fold decrease (P < 0.05) in protein phosphotyrosine content in the gastric mucosa. Ulceration induced no immediate change in superoxide dismutase (SOD) activity, 30% increase (P < 0.05) in catalase activity, 2.3-fold inhibition (P < 0.05) of glutathione peroxidase, 3.3-fold increase (P < 0.05) in hydroxyl radical content, and 2.3-fold decrease (P < 0.05) in zinc level in gastric mucosa. NOS activity was three times higher in gastric mucosa cells after cold stress. Following ulceration, PTK activity increased in plasma membranes and reached a maximum on day 4 after stress (twofold increase, P < 0.05), but remained inhibited (1.6-3-fold decrease on days 3, 4 and 5, P < 0.05) in the cytosol. Tyrosine phosphatases remained inhibited both in membranes and cytosol (1.5-2.4-fold, P < 0.05). NOS activity remained increased on days 1, 2 and 3 (3.8-, 2.6-, 2.2-fold, respectively, P < 0.05). Activity of SOD increased 1.6 times (P < 0.05) days 4 and 5 after stress. Catalase activity normalized after day 2. Glutathione peroxidase activity and zinc level decreased (3.3- and 2-fold, respectively, P < 0.05) on the last day. Activity of 2',5'-oligoadenylate synthethase increased 2.8-fold (P < 0.05) at the beginning, and 1.6-2.3-fold (P < 0.05) during ulcer recuperation, and normalized on day 5, consistent with slowing of inflammation processes. CONCLUSION: These studies show diverse changes in total tyrosine kinase activity in gastric mucosa during the recovery process. Oxidative and nitrosative stress during lesion formation might lead to the observed reduction in tyrosine phosphorylation during ulceration.