ABSTRACT
O infarto agudo do miocárdio (IAM) é a maior causa de mortalidade no mundo. A oclusão coronária determina a necrose completa de cardiomiócitos (células musculares cardíacas) durante as primeiras horas do IAM. Porém, mesmo após a perda de massa de miocárdio viável cessar, a região infartada pode se expandir ou contrair no decorrer das primeiras semanas, afetando o prognóstico dos pacientes. Alguns tratamentos podem auxiliar na recuperação e melhoria do prognóstico desses pacientes, como o uso de estatinas e antiplaquetários, que quando utilizados em conjunto, proporcionam efeitos sinérgicos. O presente estudo investigou e comparou, através da óptica da metabolômica global multiplataforma, tratamentos concomitantes de estatinas (sinvastatina ou rosuvastatina) e antiplaquetários bloqueadores do receptor de ADP (clopidogrel ou ticagrelor), em pacientes que sofreram IAM. Foram coletadas amostras de plasma e urina de cerca 40 pacientes tratados com clopidrogrel e sinvastatina ou ticagrelor e rosuvastatina no Hospital São Paulo em diferentes períodos (basal, 1 mês e 6 meses após IAM). Amostras de plasma (basal e 1 mês) foram analisadas por RPLC-MS nos modos de ionização positivo e negativo, GC-MS e CEMS. Amostras de urina (basal, 1 mês e 6 meses) foram analisadas por RPLC-MS no modo de ionização positivo e HILIC-MS nos modos de ionização positivo e negativo. A abordagem metabolomica global multiplataforma evidenciou alterações no metabolismo de diferentes vias pelos dois tratamentos. Os dois tratamentos proporcionaram um efeito pronunciado no metabolismo de diferentes lipídios, como glicerolipídios, esfingolipídios, glicerofosfolipídios e ácidos graxos, sendo que a combinação rosuvastatina e ticagrelor resultou num efeito mais acentuado. Já o tratamento com clopidogrel e sinvastatina alterou de maneira mais pronunciada o metabolismo de aminoácidos ramificados e de acilcarnitinas de cadeia curta. Observou-se ainda a alteração de possíveis biomarcadores relatados na literatura como associados a problemas cardiovasculares, como hipoxantina, ácido 2-hidroxibutírico, algumas espécies de ceramidas, fosfatidilcolinas e acilcarnitinas de cadeia curta
cute myocardium infarction (AMI) is the main mortality cause in the world. The coronary occlusion determines the complete necrosis of cardiomyocytes (cardiac muscle cells) during the first hours of AMI. However, even after the loss of viable myocardial mass ceases, the infarcted area may still expand or contract during the first weeks after AMI, affecting the patient prognosis. Some treatments may assist patient recovery and improve prognostic, such as statins and antiplatelets which, when combined, provide synergic effects. This study investigated and compared, by untargeted multiplatform metabolomics, simultaneous treatments of statins (simvastatin or rosuvastatin) and ADP receptor antagonist antiplatelets (clopidogrel or ticagrelor) in patients that suffered AMI. Plasma and urine samples from around 40 patients treated with clopidogrel and simvastatin or ticagrelor and rosuvastatin were collected in Hospital Sao Paulo at different time points (basal, 1 month, 6 months after AMI). Plasma samples (basal and 1 month) were analyzed by RPLC-MS in positive and negative ionization modes, GC-MS and CE-MS. Urine samples (basal, 1 month, 6 months) were analyzed by RPLC-MS in positive ionization mode and by HILIC-MS in positive and negative ionization modes. The untargeted multiplatform metabolomics approach has shown that different metabolic pathways have been altered by the two treatments. Both treatments had a profound impact on the metabolism of different lipids, such as glycerolipids, sphingolipids, glycerophospholipids, and fatty acids. However, the combined treatment using rosuvastatin and ticagrelor impacted the most the lipid pathways. On the other hand, clopidogrel and simvastatin treatment affected more intensily the branched chain amino acids and short chain acylcarnitines metabolisms. Reported biomarkers in the literature related to cardiovascular diseases were also observed in this study, such as hypoxanthine, 2-hydroxybutyric acid, some species of ceramides, phosphatidylcholines and short chain acylcarnitines
Subject(s)
Humans , Male , Female , Platelet Aggregation Inhibitors/analysis , Platelet Aggregation Inhibitors/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/analysis , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Simvastatin/analysis , Metabolomics/classification , Myocardial Infarction/pathology , Cardiovascular Diseases , Purinergic P2Y Receptor Antagonists , Rosuvastatin Calcium/analysis , Amino Acids/adverse effectsABSTRACT
Se realizó un estudio prospectivo para conocer la prevalencia de aloinmunización contra células sanguíneas en 30 mujeres jóvenes nulíparas, sin antecedentes de transfusiones sanguíneas ni abortos espontáneos, sometidas a un aborto provocado antes de las 12 semanas de gestación. Se determinó la presencia de aloanticuerpos contra antígenos eritrocitarios, leucocitarios y plaquetarios, antes y 6 meses después del aborto. No se detectaron anticuerpos eritrocitarios en ningún caso. En el estudio inicial se detectaron anticuerpos contra leucocitos y/o plaquetas en el 30 % de los casos, y 6 meses después del aborto en el 33,33 %. Al caracterizar los anticuerpos de la muestra inicial se determinó que en el 16,66 % de las mujeres eran anti HLA y en el 13,33 % específicos de granulocitos; en la muestra final, en el 13,33 % eran anti HLA, en el 16,66 % específicos de granulocitos y en el 3,33 % específicos de plaquetas. No se encontró relación entre el número de embarazos y la presencia de aloanticuerpos.
A prospective study was conducted to know the prevalence of alloimmunizations against blood cells in 30 nulliparous young women without previos history of blood transfusions or spontaneous abortions that underwent induced abortion before the 12 weeks of gestation. The presence of alloantibodies against erythrocytic , leukocytic and platelet antigens was determined before and 6 months after abortion. No erythrocytic antibodies were detected in any case. In the initial study, antibodies against leukocytes and/or platelets were detected in 30 % of the cases, and 6 months after abortion in 33.33 %. On characterizing the antibodies in the initial sample, it was determined that 16.66 % of the women had anti-HLA antibodies, whereas 13.33 % had granulocyte-specific antibodies. In the final sample, 13.33 % had anti-HLA, 16.66 % had granulocyte-specific and 3.33 % platelet-specific antibodies. No relation was found between the number of pregnancies and the presence of alloantibodies.