摘要:
On a préparé des zymogènes et des variantes d'activateur de plasminogène tissulaire (t-PA0), ainsi qu'une variante fibrinolytiquement active de t-Pa présentant une modification d'amino acides au niveau d'un site situé à l'intérieur du domaine de protéase de t-PA par comparaison avec le t-PA de type sauvage correspondant, ladite modification rendant la variante zymogène en présence de fibrinogène dégradé par plasmine, et/ou spécifique à la fibrine (ou caillot de plasma), par comparaison avec le t-PA de type sauvage correspondant. On peut préparer des séquences d'ADN codant les zymogènes et des variantes, ainsi que des vecteurs d'expression incorporant les séquences d'ADN, et des cellules hôtes transformées à l'aide des vecteurs d'expression. On peut utiliser les zymogènes et les variantes dans une préparation pharmaceutique pour traiter une maladie ou un état vasculaire, ou pour empêcher le dépôt ou la formation ou reformation de fibrine par adhérence chez des mammifères.
摘要:
Compositions and methods are disclosed for stimulating or inhibiting angiogenesis and/or cardiovascularization in mammals, including humans. Pharmaceutical compositions are based on polypeptides or antagonists thereto that have been identified for one or more of these uses. Disorders that can be diagnosed, prevented, or treated by the compositions herein include trauma such as wounds, various cancers, and disorders of the vessels including atherosclerosis and cardiac hypertrophy. In addition, the present invention is directed to novel polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.
摘要:
Compositions and methods are disclosed for stimulting or inhibiting angiogenesis and/or cardiovascularization in mammals, including humans. Pharmaceutical compositions are based on polypeptides or antagonists thereto that have been identified for one or more of these uses. Disorders that can be diagnosed, prevented, or treated by the compositions herein include trauma such as wounds, various cancers, and disorders of the vessels including atherosclerosis and cardiac hypertrophy. In addition, the present invention is directed to novel polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.
摘要:
A leukemia inhibitory factor antagonist, alone or in combination with an endothelin antagonist, may be used for treatment of heart failure. The antagonist(s) are administered in a chronic fashion, in therapeutically effective amounts, to achieve this purpose.
摘要:
The invention concerns tissue plasminogen activator (t-PA) variants which are glycosylated at any of positions 103-105, and are devoid of functional carbohydrate structure at position 117 of wild-type human t-PA amino acid sequence. The variants have extended circulatory half-life and substantially retained fibrin binding, or improved in vivo fibrinolytic potency, as compared to wild-type human t-PA.
摘要:
Methods of enhancing myocardial contractility and cardiac performance in a mammal with congestive heart failure are disclosed. In a first method a mammal with congestive heart failure is treated by administering to the mammal an effective amount of a combination of growth hormone (GH) and insulin-like growth factor (IGF-I). A second method comprises administering to the mammal an effective amount of a combination of GH and IGF-I in the presence of an ACE inhibitor. This method results in enhancement of myocardial contractility and cardiac performance above the level achieved with ACE inhibition alone. Preferably the mammal is a human.