Pathological interactions between the endothelin-1 and the angiotensin- converting enzyme among Tunisian coronary patients.

BACKGROUND: The correct understanding of the biochemical and metabolic interactions between coronary risk factors contribute to the exploration of cardiovascular pathophysiology and improves therapeutic care. The aim of this study was to explore the endothelin-1 (ET-1) concentration and the angiotensin converting enzyme (ACE) activity among Tunisian patients with coronary heart disease, and to investigate the metabolic relationships between these two markers,… and to assess the possible relationship between them and the different risk factors. In this present study, ET-1 concentration was determined by an analytical method (High Performance Chromatography, coupled by Mass Spectrometry), ACE activity was measured by a kinetic method for patients and healthy controls. These subjects (157 patients and 142 controls) beneficed also by a biochemical exploration (lipid, apolipoproteins and glucose profiles) to quantify cardiovascular risk. RESULTS: A statistically significant increase of the ET-1 concentration was found among patients compared to healthy controls (15.2 ± 5.3 nM vs 7.1 ± 2.7 nM, p < 0,00001). For the ACE activity, in spite the treatment of the majority of patients (97%) with ACE inhibitors, this activity was statistically elevated in patients compared to healthy subjects (86.7 ± 25.4 IU/L vs 42.8 ± 12.1 IU/L, p < 0.00001). Furthermore, a statistically positive correlation was identified between these two cardiac markers (r = 0.68 p < 0.00001). CONCLUSION: The study of the metabolic relationship between the ET-1 and ACE among coronary patients reveals other therapeutics targets.

Relationship between the A(8002)G intronic polymorphism of pre-pro-endothelin-1 gene and the endothelin-1 concentration among Tunisian coronary patients.

BACKGROUND: Acute coronary syndromes (ACS) are complex and polygenic diseases which are a real problem of public health. These syndromes require multidisciplinary studies to understand the pathogenesis mechanisms. Our study aims to evaluate the endothelin-1 (ET-1) serum concentration in Tunisian coronary compared to controls healthy, as well as the study of the impact of an intronic polymorphism A (8002) G of pre-pro-endothelin-1 Gene (inactive precursor of ET-1) on the change in serum endothelin-1 and in the susceptibility to Acute coronary syndrome (SCA). METHODS: Our samples were subdivided into coronary patients (157) and healthy subjects (142). The quantification of the ET-1 concentration was performed by high performance liquid chromatography, the identification of the different genotypes of the polymorphism A(8002)G was made by PCR-RFLP. The association between the ET-1 concentration and identified genotypes was realized by adapted software for descriptive statistics, Statistical Package for the Sociological Sciences (SPSS v 21.0). RESULTS: Our study showed that the concentration of ET-1 was significantly higher in patients compared to controls and that the mutated allele prevails in patients F (G) = 0.78 and there is a minority in controls F (G) = 0.3. Secondly the homozygous genotype GG is associated with higher concentrations of ET-1 in patients and controls, heterozygous genotype AG is associated with intermediaries' values and AA genotype is related to lower values. CONCLUSION: Although the polymorphism studied is an intronic polymorphism, it is involved in the change in serum concentration of ET-1 and is a candidate gene in susceptibility to SCA. Cardiovascular diseases are "polygenic" pathology and do not obey of the law for transmission of Mendel.

Metabolic interactions between hyperhomocysteinemia and endothelin-1 among Tunisian patients with acute coronary diseases.

BACKGROUND: Acute coronary syndromes (ACS) are complex and polygenic diseases which are a real problem of public health. These syndromes require multidisciplinary studies to understand the pathogenesis mechanisms and metabolic interactions between different risk factors.This study aimed to explore the variation of two coronary risk parameters not mentioned by Framingham cohorts, hyperhomocysteinemia and endothelin-1 (ET-1) in Tunisian coronary and the study of the variation of these parameters based on various cardiac risk factors and metabolic relationship between them.To 157 coronary and 142 healthy subjects, the concentration of homocysteine was quantified by fluorescence polarization immunoassay; the concentration of ET-1 was measured by an analytical technique, the High Performance Liquid Chromatography (HPLC) coupled with mass spectrometry. RESULTS: Our study showed that homocysteine and ET-1 were significantly higher in patients compared to healthy subjects (24.40 ± 12.5 µmol/L vs 7.44 ± 2.5 µmol/L p <0.00001) for homocysteine and (15.2 ± 5.3 nmol/L vs 7.1 ± 2.7 nmol/L, p <0.00001) for ET-1. On the other hand, homocysteine varies according to tobacco and diabetes while ET-1 depends on the sex, hypertension, smoking, obesity and dyslipidemia and a statistically negative correlation was shown between homocysteine and ET-1 in coronary patients (r = -0.66 p <0.00001). CONCLUSION: The study of the variation of these two parameters in coronary patients and metabolic exploration of the relationship between homocysteine and ET-1 according to various risk factors and the interactions between themselves facilitates the decision of therapeutic treatment.

Metabolic interactions between hyperhomocysteinemia and endothelin-1 among Tunisian patients with acute coronary diseases

BACKGROUND: Acute coronary syndromes (ACS) are complex and polygenic diseases which are a real problem of public health. These syndromes require multidisciplinary studies to understand the pathogenesis mechanisms and metabolic interactions between different risk factors.This study aimed to explore the variation of two coronary risk parameters not mentioned by Framingham cohorts, hyperhomocysteinemia and endothelin-1 (ET-1) in Tunisian coronary and the study of the variation of these parameters based on various cardiac risk factors and metabolic relationship between them.To 157 coronary and 142 healthy subjects, the concentration of homocysteine was quantified by fluorescence polarization immunoassay; the concentration of ET-1 was measured by an analytical technique, the High Performance Liquid Chromatography (HPLC) coupled with mass spectrometry. RESULTS: Our study showed that homocysteine and ET-1 were significantly higher in patients compared to healthy subjects (24.40 ± 12.5 µmol/L vs 7.44 ± 2.5 µmol/L p <0.00001) for homocysteine and (15.2 ± 5.3 nmol/L vs 7.1 ± 2.7 nmol/L, p <0.00001) for ET-1. On the other hand, homocysteine varies according to tobacco and diabetes while ET-1 depends on the sex, hypertension, smoking, obesity and dyslipidemia and a statistically negative correlation was shown between homocysteine and ET-1 in coronary patients (r = -0.66 p <0.00001. CONCLUSION: The study of the variation of these two parameters in coronary patients and metabolic exploration of the relationship between homocysteine and ET-1 according to various risk factors and the interactions between themselves facilitates the decision of therapeutic treatment.

Low erythrocyte catalase enzyme activity is correlated with high serum total homocysteine levels in Tunisian patients with acute myocardial infarction.

BACKGROUND: An imbalance between pro-oxidants and antioxidant systems has been suggested to be implicated in the physiopathology of acute myocardial infarction (AMI). We aimed to evaluate the antioxidant capacity in Tunisian patients and to assess the possible relationship between erythrocyte catalase enzyme activity and hyperhomocysteinaemia. METHODS: 108 patients with AMI and 81 healthy subjects were enrolled in this study. Catalase erythrocyte enzyme activity was determined spectrophotometrically whereas "total antioxidant status" (TAS) concentration was measured by a commercially available method. Serum total homocysteine (tHcy) level was determined by a fluorescence polarization immunoassay (FPIA). Lipid peroxidation was measured with a fluorimetric method as "thiobarbituric acid reactive substances" (TBARS). RESULTS: Compared with healthy subjects, patients with AMI had significantly lower catalase activity (P<0.001), TAS concentrations (P<0.001), and significantly higher serum tHcy (P<0.001) and TBARS levels (P<0.001). Erythrocyte catalase enzyme activity was negatively correlated with serum tHcy and TBARS while serum tHcy and TBARS were in positive correlation. Furthermore, the unbalance between pro-oxidants and antioxidants seems to be more aggravated in patients with Q wave AMI compared to patients with non-Q wave AMI. CONCLUSION: Our results suggest the involvement of hyperhomocysteinaemia in the drop of erythrocyte catalase activity related to myocardial ischemia reperfusion. Hyperhomocysteinaemia may increase the myocardial wall dysfunction under ischemia reperfusion by excessive production of reactive oxygen species which is made evident by increased lipid peroxidation. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1623509866881834.

[Metabolic interactions between the hyperhomocysteinemia and angiotensin-1 converting enzyme activity in Tunisian patients with coronary heart disease]. / Les interactions métaboliques entre l'hyperhomocystéinémie et l'activité de l'enzyme de conversion de l'angiotensine 1 chez les coronariens tunisiens.

Hyperhomocysteinemia and hyperactivity of the angiotensin-1 converting enzyme (ACE1) are considered two unconventional coronary risk factors. The study of the variation of these two biochemical parameters in coronary patients and metabolic investigation of the relationship between these two markers has a fundamental interest. In this context, 110 patients and 80 control subjects are recruited for our study. Homocystenemia was determined by fluorescence polarization immunoassay (FPIA). ACE1 activity was measured by kinetic method. An increased of homocysteinemia and ACE1 activity was observed in patients compared with control subjects (Hcy: 23±18 µmol/L vs 9±4 µmol /L; p<0.0001); (ACEI: 81±18 UI/L vs 55±18 UI/L; p<0.0001). These two markers varied differently according to the risk factors. Homocysteinemia, was negatively correlated with ACE1 activity (r = -0.36; p<0.001). The negative correlation between these two markers reflects metabolic and physiopathological interactions.

The pro-oxidant effect of angiotensin-1 converting enzyme in Tunisian patients with coronary heart disease.

BACKGROUND: Evaluation and investigation of the pro-oxidant role of the angiotensin-1 converting enzyme among Tunisian coronary. MATERIALS AND METHODS: In the present study the angiotensin-1 converting enzyme (ACE1) was determined by a kinetic method for coronary and witness populations. These subjects (117 patients and 86 controls) beneficed also by an enzymatic determination of superoxide dismutase (SOD), glutathione peroxidase (GPx) and total antioxidant status (TAS) to reveal the atherogenic effects of these radical species and investigate their interactions with ACE1. RESULTS. The determination of ACE1 activity showed a significant increase in patients compared to controls (82.24 +/- 21.6 vs 49.23 +/- 12.85 UI/L, p <0.000001). Statistical tests have shown negative correlations between the ACE 1 activity and the antioxidant defense markers (SOD, GPx and TAS). CONCLUSION: In addition to its vasoconstrictor role, ACE1 can be considered as a pro-oxidant enzyme, these two effects combine in the genesis and the complications of cardiovascular diseases. (www.actabiomedica.it)