RESUMEN
Plasma prekallikrein is the liver-derived precursor of the trypsin-like serine protease plasma kallikrein (PK) and circulates in plasma bound to high molecular weight kininogen. The zymogen is converted to PK by activated factor XII. PK drives multiple proteolytic reaction cascades in the cardiovascular system such as the intrinsic pathway of coagulation, the kallikrein-kinin system, the fibrinolytic system, the renin-angiotensin system and the alternative complement pathway. Here, we review the biochemistry and cell biology of PK and focus on recent in vivo studies that have established important functions of the protease in procoagulant and proinflammatory disease states. Targeting PK offers novel strategies not previously appreciated to interfere with thrombosis and vascular inflammation in a broad variety of diseases.
Asunto(s)
Bradiquinina/metabolismo , Calicreína Plasmática/metabolismo , Animales , Aprotinina/química , Coagulación Sanguínea , Hemorragia Cerebral/metabolismo , Proteínas del Sistema Complemento , Cisteína/química , Retinopatía Diabética/metabolismo , Disulfuros/química , Factor XIIa/química , Fibrinólisis , Hemostasis , Humanos , Inflamación , Sistema Calicreína-Quinina , Calicreínas/química , Cininas/química , Ratones , Oligonucleótidos Antisentido/química , Péptidos/química , Estructura Terciaria de Proteína , Proteolisis , Sistema Renina-Angiotensina , Transducción de Señal , Trombosis/metabolismo , Tripsina/químicaRESUMEN
Therapeutic myocardial angiogenesis by means of transient overexpression of angiogenic growth factors is a potential treatment modality for severe ischemic heart disease. This study was undertaken in the rat to examine effects of phVEGF-A(165) myocardial transfection in terms of dose-response as regards the number of hVEGF-A expressing cells on one hand and on the other angiogenesis. Non-surgical echocardiography-guided intramyocardial injection of phVEGF-A(165) was done into normoxic or hypoxic (10% O(2)) rats. Cardiomyocytes expressing VEGF-A protein, capillary morphology and density were determined after 5 days. VEGF protein expression was seen in rat cardiomyocytes located around the tip of the injection scar and increased dose-dependently (p<0.05). Microvessel density also increased dose-dependently with phVEGF(165) (p<0.05) and with hypoxia (p<0.05). No vascular tumours were observed. In conclusion, direct intramyocardial injection of phVEGF-A(165) in the rat results in a dose-dependent increase both in transfected hVEGF-A protein producing cells and in angiogenesis.
Asunto(s)
Factores de Crecimiento Endotelial/genética , Factores de Crecimiento Endotelial/uso terapéutico , Miocardio/metabolismo , Neovascularización Fisiológica/efectos de los fármacos , Animales , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/patología , Relación Dosis-Respuesta a Droga , Factores de Crecimiento Endotelial/metabolismo , Expresión Génica , Terapia Genética/métodos , Humanos , Hipoxia/terapia , Inyecciones Intramusculares , Masculino , Isquemia Miocárdica/terapia , Miocardio/citología , Miocardio/patología , Plásmidos/administración & dosificación , Plásmidos/genética , Ratas , Ratas Sprague-Dawley , Transfección , Factor A de Crecimiento Endotelial VascularRESUMEN
Headache is a common symptom among children and teenagers. Both bruxism and muscle and joint tenderness have been found in children with headache. Children with migraine headache report more temporomandibular disorder (TMD) symptoms than do those with tension-type headache. The aim of the present study was to investigate the association of different types of headache with TMD and sex in children. Altogether 297 randomly selected schoolchildren aged 13-14 years participated in a blind study setting. There were no statistically significant differences between the headache groups with regard to TMD signs, although the migraine and migraine-type headache groups had the highest percentage of subjects with more severe TMD signs. Nor were there any statistical differences between sexes or between the headache groups with regard to subjective symptoms of TMD. The present results with children differed from earlier results with adults. First, no association was found between tension headache and TMD, and, second, no sex difference in TMD children was observed at this age.