Association of transforming growth factor-ß1 gene polymorphisms with genetic susceptibility to acute myocardial infarction.

INTRODUCTION: Transforming growth factor beta 1 (TGF-ß1) gene plays an important role in acute myocardial infarction (AMI); however, little is known about the relation of variations within the gene and risk of cardiovascular diseases. In this study, the authors evaluated the influence of TGF-ß1 polymorphisms on the onset and progression of AMI in Iranian patients comparing with healthy individuals. METHODS: Genomic DNA and peripheral blood mononuclear cells of 900 enrolled patients with AMI and 900 control subjects were extracted. The -509 C/T, 868T/C, 913G/C and 11929C/T TGF-ß1 polymorphisms were detected. The messenger RNA (mRNA) expression and serum levels of TGF-ß1 were analyzed by real-time reverse-transcriptase polymerase chain reaction and ELISA, respectively. RESULTS: The frequency of "T" allele in -509 C/T, "C" allele in 868T/C, "C" allele in 913G/C and "T" allele in 11929C/T polymorphisms were significantly higher in the patients than control subjects (P < 0.001). There were significant differences in circulating levels of TGF-ß1 in the patients than in control subjects (P < 0.001). These concentrations are associated with its gene polymorphism. The mRNA expression levels of TGF-ß1 were significantly higher in the patient serums compared with controls (P < 0.001). CONCLUSIONS: Our results confirmed the association between the TGF-ß1 polymorphisms and risk of AMI, which suggest that genetic polymorphisms in TGF-ß1 might be helpful for determining susceptibility to AMI in Iranian patients. There are also significant relationship between serum TGF-ß1 and occurrence of AMI. In addition, susceptibility to AMI might be related to TGF-ß1 gene expression, which affects its serum levels.

Association of Helicobacter pylori infection with acute myocardial infarction.

OBJECTIVES: Helicobacter pylori infection has been linked to cardiovascular diseases (CVD) and several studies have reported its positive association with inflammatory response after acute myocardial infarction (AMI). On account of the importance of the inflammatory process in the development of CVD, we decided to examine the seroprevalence of H. pylori, the prevalence of CVD risk in the more virulent strains bearing the cytotoxin-associated protein (CagA), and the changes in C-reactive protein (CRP) as an inflammatory marker in Iranian patients with AMI. METHODS: A case-control study was designed to determine the seropositivity status of H. pylori and CagA in blood samples obtained from 500 patients with AMI and 500 control individuals without any evidence of clinical CVD. Serum and peripheral blood mononuclear cells were analyzed using the enzyme-linked immunosorbent assay and western blotting methods, respectively. CRP levels were also measured in all individuals. RESULTS: The prevalence of H. pylori infection and CagA status were significantly higher among the patients with AMI than the controls (66 vs. 20% and 75.7 vs. 30%, respectively); the odds ratio was 2.57 (95% confidence interval 1.89-3.49). CRP levels were significantly different in the patients compared with the controls (5.02±1.04 mg/l vs. 2.41±0.9 mg/l, respectively). CONCLUSION: Our results confirmed that the patients with AMI had a significantly higher prevalence of H. pylori infection and CagA seropositivity than the control population. Infection with H. pylori may influence AMI, which in our findings shows an association between H. pylori seropositivity and AMI through an inflammatory process.

Activation of mitogen activated protein kinases in post-infarcted patients.

Activation of mitogen-activated protein kinases (MAPKs) signaling cascade are important pathophysiologic regulators during the development of acute myocardial infarction (AMI). In present study, we designed to monitor the activity of these MAPKs in Iranian patients with AMI comparing with controls. The degree of activation (phosphorylation) of p38 kinase, p44/42 extracellular regulated kinase, and c-Jun N-terminal kinase (JNK1/2) and their corresponding activity levels were analyzed in 258 patients with AMI and 250 normal subjects. The expression of p38α mRNA was determined. These analysis were carried out immediately and 12 h after AMI. Activity of p38 and JNK1/2 MAPKs were significantly increased in patients with AMI than controls immediately after infarction. These activities were reduced during 12 h after AMI. However, there were no statistically differences in activation and activity of p44/42 in the patients and controls. The mRNA expression of p38α was increased in the patients comparing with controls. Results of this study indicate that these MAPKs signaling pathway might be activated by AMI which signal transduction involves kinase phosphorylation and play important roles in their activity. Elevated activity of p38 and JNK1/2 MAPKs suggests that they may potentially play significant roles in AMI.

Matrix metalloproteinase: investigation from gene to protein as effective factor in myocardial infarction.

Current evidence indicates that extracellular matrix (ECM) remodeling is a component of acute myocardial infarction (AMI) and matrix metalloproteinase (MMP) has a role in early atherosclerosis, plaque rupture and myocardial infarction (MI). The necessity of inhibition of ECM remodeling and subsequent injuries in patients with AMI suggests that MMP might be involved in this task. Therefore, we investigated the activities of MMP-1, -2, -3, and -9 which play an important role in AMI. Plasma and peripheral blood mononuclear cells (PBMCs) of 50 patients with AMI were isolated from peripheral blood after the onset of AMI within 24 h, comparing with 50 control subjects. The active form of MMPs was measured by enzyme linked immunosorbent assay (ELISA); MMP proteins presence and expression by immunoblotting and zymography analysis; and mRNA expression of MMPs by real time reverse transcriptase polymerase chain reaction. Plasma concentrations of MMPs increase in patients rather than control subjects. Gel zymography revealed 43, 66, 45, and 83 kDa molecular weight bands which consistent with active MMP-1, -2, -3, and -9, respectively, exhibiting gelatin-degrading activity in both patient and control subjects. No up-regulation of mRNA expression was found. To our knowledge, it is the first monitoring of MMP gene and protein expression and also circulating active MMPs in Iranian patients with AMI and normal subjects. Up-regulation of MMPs activity is common in the falling myocardium and missing up-regulation of transcription indicates that protein levels of MMPs were regulated at the post transcriptional level.

The effect of human chorionic gonadotropin treatment on recipient mouse germ cell proliferation following spermatogonial stem cell transplantation of neonatal donor mice.

Spermatogonia are the male germ line stem cells whose life long expansion is needed for permanent production of spermatozoa. The present study was designed to examine the effect of hCG treatment on germ cell proliferation following stem cell transplantation in mice. Spermatogonial stem cells were isolated from neonatal mice testes and characterized by alkaline phosphatase, immunoreactivity and morphological analysis. hCG was injected into normal and cell transplanted mice. We then evaluated the testosterone levels and cell number in normal mice. After that, cyclin B1 gene expression was investigated in transplanted mice. Different doses of busulfan were injected to investigate the effects of chemotherapy on morphological criteria and preparation of recipient mice for transplantation. In this report we show proliferative potential of spermatogonial stem cells after cytotoxic treatment, transplantation efficiency by semi-quantitative RT-PCR, and hCG effect on stem cell regeneration in normal mice and following cell transplantation. The results indicate that spermatogonial stem cells can proliferate after transplantation, and the efficiency of their transplantation depends on hormonal treatment. Therefore, hormonal treatment after stem cell transplantation will be a powerful avenue for increasing the efficiency of transplantation and fertility restoration.