Cox 1 +/- cox 2 -/- associados à redução do tempo de oclusão na artéria carótida e aumento dos níveis de pai-1

Luane de Araújo Parreiras

Introdução
- Estudos sobre COX-1 e COX-2; - Tromboxano A2; - Prostaciclina; - PAI-1; - Inibidores seletivos da COX-2; - AINE’s

Objetivo
Explicar o mecanismo de aumento de eventos trombóticos associados ao genótipo COX-1 +/- COX-2 -/-

Desenvolvimento
- Infarto do miocárdio e outros eventos trombóticos; - PAI-1 em camundongos; -Camundongos submetidos à dietas hiperlipidêmicas; - Atuação da vitronectina; - Deficiência da PAI-1 em humanos

Sobrevida de camundongos com genótipo COX-1 +/COX-2 -/-

Tempo de oclusão

Fig. 2. COX-1+/-COX-2-/- genotype is associated with a shortened time to occlusion in the Rose Bengal carotid artery injury model. (A) C57BL/6J mice. Data are means ± SD of 8–17 mice per group. +P < 0.01, ++P < 0.001 compared with wild-type control mice; *P < 0.01, **P < 0.001, ***P < 0.001 compared with control mice of the same genotype. (B) B6;129 mice. Data are the means ± SD of five to eight mice per group. +P < 0.001 compared with wild type mice; *P < 0.002, **P < 0.001 compared with control mice of the same genotype.

Metabólitos da PGI2 e tromboxano A2

Redução da fibrinólise

Western blot

(B) Western blots for PGI synthase, PAI-1, COX-1, COX-2 and actin using protein extracts of aorta from wild-type, COX-1+/+ COX-2-/- and COX-1+/-COX-2-/- mice on a C57BL/6J genetic background. Numbers are fold change compared with the expression of the protein in wild-type mice.

Níveis plasmáticos de PAI-1

Fig. 5. Plasma levels of PAI-1 are higher in COX-1+/- COX-2-/- mice compared with wild-type (WT) or COX-1+/+ COX-2-/- mice. Total PAI- 1 and active PAI-1 levels were measured in the plasma of C57BL/6J mice. Data are the means ± SD of 12 mice for active PAI-1 and 20 mice for total PAI-1. *P < 0.01 compared with wild-type mice active PAI-1; **P < 0.001 compared with wild-type mice total PAI-1.

Tempo de oclusão com Anti PAI-1

Fig. 6. The shortened time to occlusion in COX-1+/- COX-2-/- mice