Myocardial infarction is a complex and multifactor disease in which the cellular and molecular mechanisms contributing to myocardial injury need to be more defined. In our data, investigation about oxidative stress parameters shows an increased serum TBARS level, as a lipid peroxidation marker, and a drop in the total antioxidant capacity in patients with AMI compared to healthy subjects. According to our observation, Pasupathi et al. have considered that the increased serum TBARS is a consequence to excessive ROS generation. The authors reported it to the raised xanthine oxidase activity under ischemia reperfusion . Other enzymatic and cellular sources are suggested to be implicated in ROS generation. Some of these are related to the uncoupling of mitochondrial electron transport in consequence to the lack of oxygen supply under ischemia, or to the impairment of NO synthase activity .
In our study, we observed a decrease in erythrocyte catalase activity in patients compared to controls. Accumulation of hydrogen peroxide under ischemia reperfusion can also inhibit antioxidant enzymes (high substrate inhibition) and alter its enzymatic conformation. According to Senthil et al., the decreased activity of catalase in patients with CHD could be due to the inactivation of this enzyme by cross linking or to the impairment of NO synthase. Nitrite oxide (NO) can bind reversibly to ferric iron, inhibiting afterwards catalase activity [16, 17]. Erythrocyte catalase activity tended to decrease in patients with hypertension and smoking as the major cardiovascular risk factors. Cigarette smoke is an abundant source of free radicals. It contains more than 1015 free radicals including superoxide anion and NO. Chemical oxidants in cigarette smoke can cause the oxidation of DNA encoding for antioxidant proteins . On the other hand, essential Hypertension is subjected to increased oxidative stress. It may damage the endothelium and impair endothelium-dependent vascular relaxation. ROS can act on angiotensin converting enzyme to increase its catalytic activity resulting in the increase in angiotensin II production, which, in turn, is a major endogenous inducer of NADPH oxidase. Oxidative stress, endothelial dysfunction and inflammation represent a key triad for the development and progression of Coronary heart disease [19, 20].
The imbalance between pro-oxidants and antioxidants occurred under ischemia reperfusion can be aggravated by hyperhomocysteinaemia. The moderate hyperhomocysteinaemia revealed in patients can be reported to a hereditary defect of any of the Hcy metabolic enzymes (cystathionine β-synthase, methylene tetrahydrofolate reductase) or to the depletion in folic acid and vitamin B6 or B12 . Increased serum tHcy may cause endothelial dysfunction by promoting free radicals. Homocysteine is readily oxidized. Its auto-oxidation is catalyzed by transition metal ions, such as copper leading to homocystine, homocysteine mixed disulfides and homocysteine thiolactone formation [21, 22]. Homocysteine reduces the transition metal ion (Mn+) to generate a thioyl radical (Hcy°). It is thought to react with homocysteine to generate a free radical intermediate that reduces oxygen to superoxide anion (O2°) and then to peroxide hydrogen generation [3, 23]. In our data, we have shown a negative correlation between hyperhomocysteinaemia and erythrocyte catalase activity in patients with AMI. Homocysteine has the ability to bind proteins and to form disulphide bridges with cysteine residues within proteins. Milton N et al. suggest that modification of cysteine residues by Homocysteine may alter the enzymatic activity of catalase . The excessive generation of ROS under ischemia reperfusion can affect the red cell metabolism and the possible hemolysis when more than 98% in blood catalase is located in erythrocytes . Now this is in line with other works suggesting that Hcy can affect the antioxidant enzyme expression. Nanako et al. reported that homocysteine reduced the expression of superoxide dismutase (SOD) mRNA in cultured rat smooth muscle cells . Other studies showed a positive correlation between plasma Hcy and genomic damage related to DNA hypomethylation which let us to suggest that Hcy can exert genotoxic effects on DNA genes encoding for antioxidant proteins .
Reactive oxygen species generated by Hcy auto-oxidation are involved through Fenton type reaction in lipid peroxidation. The serum tHcy and TBARS levels were found higher in patients’ with electrocardiogram presenting Q wave AMI compared to patients with non Q wave MI. Myocardial Infarction with Q wave can be used as a predictor of morbidity and mortality patterns after Myocardial events. Desmarais PL and al showed that individuals who had non-Q wave MI had better survival rates for the first 3 years after myocardial rehabilitation than did those who had Q wave MI . Excessive lipid peroxidation can be directly involved in the myocardial necrosis manifesting as a myocardial wall dysfunction. Polyunsaturated fatty acids (PUFAs) such as arachidonic, linolenic and linoleic acids present the major targets for free radical attack. It has also been suggested that lipid peroxidation might proceed not only in plasma membranes but also in the nuclear membranes close to chromosomes, due to the loss of membrane integrity in cell membranes consisting of phospholipids. Lipid peroxidation products, such as 4-hydroxynonenal (HNE) and Malondialdehyde (MDA) are toxic. HNE leads to a decrease in protein thiols, disturbance of calcium homeostasis, inhibition of DNA, RNA and protein synthesis, inhibition of respiration and glycolysis . Furthermore, HNE leads to mammalian cell death. It increases the expression of p53 family members as well as an increase of expression of the Bax pro-apoptotic gene . MDA is able to interact with nucleic acid bases to form several different adducts and to exacerbate DNA oxidative damage, including genes encoding for antioxidant proteins such as catalase, glutathione peroxidase and SOD.