Avaliação da atividade de enzimas que degradam nucleotídeos de adenina e ésteres de colina e estudo do perfil oxidativo em pacientes com cardiopatia isquêmica

Abstract

Ischemic heart disease (IHD) is a major cardiovascular disease. The term ischemia refers to a lack of oxygen due to inadequate perfusion, which results from an imbalance between oxygen supply and demand. The most common cause of myocardial ischemia is atherosclerotic obstructive coronary artery disease caused by rupture or ulceration of atheromatous plaque and subsequent thrombus formation. Platelets are one of the most important blood components that participate in and regulate thrombus formation by releasing active substances such as adenine nucleotides ATP and ADP. Once their action is exerted, the nucleotides are degraded by a group of enzymes called ectonucleotidases. These enzymes are responsible for the hydrolysis of ATP and ADP to AMP, and consequent formation of adenosine, a cardioprotective and anti-inflammatory molecule. Another important anti-inflammatory molecule is acetylcholine (ACh). However, ACh is rapidly hydrolyzed by the enzymes acetylcholinesterase (AChE) and tyrylcholinesterase (BuChE). Following ischemia, an elevated production of reactive oxygen species (ROS) occurs. The imbalance between ROS production and degradation may lead to an increase in oxidative stress. This study aimed to determine the activity of enzymes involved in thromboregulation, such as NTPDase, 5'-nucleotidase, E-NPP and ADA, the activity of enzymes that degrade choline esters: AChE and BuChE, as well as the parameters of oxidative stress in IHD patients and controls. Evaluation of the oxidant system was carried out by lipid peroxidation and carbonyl protein determination, and the enzymatic and nonenzymatic antioxidant defense measurements were performed in total blood, plasma, and serum of IHD patients. Results showed an increase in the NTPDase and 5'-nucleotidase activities as revealed by nucleotides hydrolysis ATP, ADP and AMP. An increase in E-NPP activity was also observed in IHD patients. However, a decrease in ADA activity was observed. Based on the results presented here we suggest that the pathological condition in IHD produced alterations in ectonucleotidase activities as a compensatory organic response, with the objective of maintaining the levels of adenosine, which is a cardioprotective molecule. An increase in the activity of enzymes that degrade choline esters (AChE and BuChE) in IHD patients was observed. Increasing total blood and serum activities of AChE and BuChE enzymes indirectly reflect reduced levels of ACh. The enhancement of local and systemic inflammatory events is observed due to the absence of the negative feedback control exerted by ACh. Regarding oxidant levels, an increase in TBARS and carbonyl protein levels was observed in acute myocardial infarction (AMI) patients when compared to the control group. The same occurred for the activities of the enzymatic antioxidants, superoxide dismutase (SOD), and catalase (CAT). However, a decrease in nonenzymatic antioxidants, such as vitamin C and vitamin E, was observed in AMI patients when compared to control. These results suggest an increase in oxidative stress in AMI, which was probably a result of the ischemic/reperfusion moment, as well as a decrease of antioxidant defenses. Furthermore, the increased antioxidant defense may act as a compensatory mechanism in consequence of the overproduction of ROS after AMI. In conclusion, IHD results in oxidative and inflamatory damages as well as an increase in the organism defenses as a compensatory response.