Metaloproteinases de matriz e incorpora????o de colesterol na lipoprote??na de alta densidade (HDL) na doen??a carot??dea

As doen??as cardiovasculares s??o a maior causa de morbimortalidade nos pa??ses emergentes, consistindo em doen??a arterial central, cerebral e perif??rica, em especial, a coron??ria e a carot??dea. Dentre os diversos fatores e marcadores de risco que atuam no desenvolvimento e no agravo dessas doen??as, encontram-se os relacionados com a aterosclerose. Este estudo avaliou a concentra????o s??rica e a atividade de metaloproteinases de matriz (MMP-1, 2, 8, 9 e 12), a incorpora????o de colesterol livre na HDL, a atividade da paraoxonase e associa????o com outros fatores em pacientes com doen??a carot??dea ateroscler??tica. M??todos. Este estudo de corte transversal avaliou, em popula????o de 65 indiv??duos portadores (32) e n??o (34) de DCA (doen??a carot??dea ateroscler??tica), determinada por ecografia vascular com doppler, ambos os sexos, idade m??dia de 51,1 (?? 6,7) anos, a exist??ncia de diferen??as entre de fatores associados ?? aterog??nese, sua rela????o com o remodelamento do endot??lio vascular e transporte reverso do colesterol. Foram padronizados e utilizados m??todos com marcadores isot??picos, ELISA e zimografia por SDS-PAGE para determina????o, identifica????o e verifica????o da atividade proteol??tica. Resultados. Foi constatado que as amostras de soro dos pacientes portadores de DCA incorporaram menos colesterol livre triciado (CL-3H) quando comparados aos pacientes NDCA (n??o portadores de DCA) e, tamb??m, que os ??ndices e demais par??metros de avalia????o do metabolismo lip??dico corroboram o fen??meno (HDL-C, r=-0,330; p=0,0606, Pearson), mostrando uma tend??ncia (HDL-C/apoA, r=0,511; p=0,0254) e rela????o positiva no grupo NDCA. Foram observadas correla????es positivas entre MMP-1 e HDL-C (r=0,6175; p=0,002, Pearson) e MMP-1 com MMP-9 (r=0,5109; p=0,0215; Pearson) e MMP-1 com CMV-IgG (r=0,619; p=0,0012; Pearson) e correla????o negativa entre MMP-9 e apoB no grupo DCA. Por ELISA foram evidenciadas, no grupo DCA, menores densidades ??pticas (DO) de MMP-2 e MMP-9. Contudo, essas mesmas MMP (2 e 9) apresentaram maior atividade proteol??tica no zimograma do grupo DCA. Conclus??o. A menor incorpora????o de CL-3H no grupo DCA indica defici??ncia no transporte reverso do colesterol, essa altera????o prejudica os mecanismos de prote????o contra a aterog??nese. Aliado a isso, observou-se redu????o das mensura????es s??ricas das MMP no grupo DCA, a qual pressup??e a participa????o dessas MMP no remodelamento vascular, principalmente, nas placas e/ou les??es ateroscler??ticas. As MMP e outros marcadores avaliados nos DCA mostraram que o evento n??o tem participa????o somente de mol??culas relacionadas ao transporte lip??dico, mas tamb??m, aquelas relacionadas ?? infec????o por CMV (citomegalovirus), evidenciadas pela presen??a de correla????o positiva entre MMP-1 e CMV-IgG. A menor incorpora????o de CL-3H, baixa DO de MMP-2 e 9, maior atividade proteol??tica no zimograma e a MMP-1 associada ?? infec????o por CMV s??o fatores a serem avaliados para utiliza????o na predi????o de risco cardiovascular em pacientes com DCA. As menores DO de MMP-2 e 9 nos DCA em contraposi????o ?? maior atividade dessas proteinases suscita a participa????o de fatores reguladores (e.g. TIMP) da atividade dessas proteinases, atuando de forma distinta daquela dos NDCA.The cardiovascular diseases are the biggest cause of morbimortality in evidence in the emerging countries; they consist into central, cerebral and peripheral arterial diseases, mainly coronary and carotidal. Among the several risk factors and markers that contribute to the development and severity of those diseases, there are that related to atherosclerosis. This study evaluates the serum concentration and activity of matrix metaloproteinases (MMP-1, 2, 8, 9 e 12), the paraoxonase activity and the association with others factors in patients with carotidal atherosclerotic disease (DCA). Methods. It was done a transversal study to evaluate, in a population of 65 individuals with (31) and without DCA (34), indicated by vascular echography with doppler, both genders, average age 51.1 (?? 6.7) years, the occurrence of differences between clinical laboratory markers and their relationship with vascular endothelium remolding and reverse cholesterol transport. It was standardized and executed methods with isotopic markers, ELISA and SDS-PAGE zymography to the determination, identification and verification of proteolytic activity. Results. From the incorporation, it was verified that the DCA patients??? serum samples assume little free cholesterol when compares to NDCA (no DCA carrier patients). Also, regarding the data of CL-3H incorporation, it was verified that the index and parameters of lipid metabolism evaluation corroborate the event (HDL-C, r=-0.330; p=0.0606, Pearson), which shows a tendency (HDL-C/apoA, r=0.511; p=0.0254) and positive relationship in the NDCA group. Besides, positive correlations between MMP-1 and HDL-C (r=0.6175; p=0.002, Pearson) and MMP-1 with MMP-9 (r=0.5109; p=0.0215; Pearson) and MMP-1 with CMV-IgG (r=0.619; p=0.0012; Pearson) and negative correlation between MMP-9 and apoB in the DCA group were observed. The ELISA demonstrates lower MMP-2 and MMP-9 optic density (DO) in DCA group. Otherwise, these same MMP (2 and 9) shows bigger digestive activity at zymogram assay in the DCA group when compared to NDCA. Conclusion. The lower incorporation of CL-3H in the DCA group drives to reverse cholesterol transport deficiency, these alterations disables the protection mechanisms against the atherosclerosis. Join to this, it was observed the serum measures reduction of MMP in DCA group that presume the participation of these MMP in the vascular remolding process, mainly on the plates or/and atherosclerotic lesions. The MMP and others markers evaluated in DCA reveal that the event does not have solely participation of molecules related to lipid transport, but also that ones related with infection with CMV (cytomegalovirus) exposed by positive correlation between MMP-1 and CMV-IgG marker. Thus, the small CL-3H incorporation, the lowest MMP-2 and 9 DO, biggest digestion of the polyacrylamide gel copolymerized with gelatin and MMP-1 when associated to CMV infection are markers that must be evaluated to predict the cardiovascular risk in DCA patients. The lower DO of MMP-2 and 9 in DCA group in opposition to the bigger activity of these proteinases give raise to participation of regulatory factors (e.g. TIMP) that run in a distinct way from NDCA group