Ana Paula Lucas Mota

Asymmetric Dimethylarginine (ADMA) in cardiovascular and renal disease

BACKGROUND Asymmetric Dimethylarginine (ADMA) is a modified amino acid formed when intracellular arginine is methylated by methyltransferases that are widely distributed throughout the body. Nitric oxide (NO) is produced from l-arginine in a reaction catalyzed by three distinct isoforms of NO synthase (NOS). NO has emerged as a mediator involved in maintenance of vascular tonus, blood pressure regulation, inhibition of platelet aggregation, leukocyte and endothelial cell interaction and vascular permeability. ADMA is an important inhibitor that competes with NOS and compromises NO synthesis. OBJECTIVE This review aims to compile articles involving renal and cardiovascular diseases in which plasma ADMA was assessed in order to clarify its role in these diseases. CONCLUSION Although current knowledge suggests that ADMA has a role in the onset of cardiovascular and renal diseases, its actions are poorly understood. Clarifying its biochemical mechanisms is essential for improving disease management and promoting better quality of life for these patients.

Mutations in methylenetetrahydrofolate reductase and in cysthationine beta synthase: is there a link to homocysteine levels in peripheral arterial disease?

Peripheral arterial disease (PAD) is an atherosclerotic disturbance characterized by a progressive obstruction of lower limb arteries. Many risk factors associated with PAD development have being reported in the literature. The present study aimed to investigate whether mutations in the methylenetetrahydrofolate reductase (MTHFR) or in the cystathionine beta synthase (CBS) genes are associated with higher levels of homocysteine and the risk of PAD in patients from Brazil. This study analyzed 39 patients with PAD and 32 without PAD in whom risk factors and C677T mutations in the MTHFR gene and both 844ins68 and T833C mutations in the CBS gene were investigated. Although higher levels of homocysteine could be observed in patients with PAD compared to controls, no association between the increase of homocysteine and the frequency of C677T, 844ins68, and T833C mutations could be observed. The results suggest that these mutations do not appear to be related to either homocysteine levels or the development of the disease. However, hyperhomocysteinemia and smoking are important factors in PAD development.

Hypercoagulability Markers in Patients With Peripheral Arterial Disease: Association to Ankle-brachial Index

Peripheral arterial disease is diagnosed by measuring the ankle-brachial index. Values lower than 0.90 define the disease being usually related to its severity. Patients with peripheral arterial disease may show a hypercoagulability state. The aim of this study was to assess hemostatic variables and to correlate them with the presence of peripheral arterial disease and its severity as assessed by ankle-brachial index values. Plasma levels of D dimer, plasminogen, prothrombin fragment 1+2, plasminogen activator inhibitor and thrombomodulin were measured in 36 patients with peripheral arterial disease (group 1) and 30 without disease (group 2). Significant differences for D dimer, plasminogen, prothrombin fragment 1+2 and plasminogen activator inhibitor type 1 between the 2 groups were found (P<0.05). Significant and inverse correlations were also observed (Pearson correlation, P<0.05) between ankle-brachial index values and levels of both plasminogen and plasminogen activator inhibitor type 1. Although there was no significant correlation between ankle-brachial index and levels of D dimer, higher D dimer values were observed in patients with lower ankle-brachial index values. The results confirm a trend to hypercoagulability and hypofibrinolysis in patients with peripheral arterial disease. Increased levels of plasminogen activator inhibitor type 1 seem to be associated with the severity of the disease, considering the inverse correlation between this inhibitor and ankle-brachial index.

Lipoproteína (a) em pacientes portadores de doença arterial obstrutiva periférica e/ou diabetes mellitus tipo 2

BACKGROUND: Peripheral arterial obstructive disease (PAOD) constitutes an excellent marker for systemic atherosclerosis and type 2 diabetes mellitus (DM2) is among the greatest risk factors for this disease. It is believed that lipoprotein (a) [Lp(a)] is linked to increased risk of atherosclerosis, although the mechanisms responsible for that are not widely known. Elevated levels of Lp(a) seem to be associated with a higher risk of coronary artery disease (CAD), as well as PAOD and cerebrovascular disease. OBJECTIVES: To assess the plasma levels of Lp(a) and other lipid parameters in patients with PAOD and/or DM2. Material and methods: Plasma levels of Lp(a), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG) and apolipoproteins A-I and B were measured in blood samples of 12 subjects carrying neither PAOD nor DM2 (control group), 17 patients with PAOD, 18 with DM2 and 19 with both PAOD and DM2. The subjects selected for this study showed homogeneity and no statistical difference for gender, age, and socioeconomic status. RESULTS: The Lp(a) showed a tendency to elevation both in groups PAOD only and PAOD + DM2 simultaneously. Significant differences were observed among the groups as to HDL-c and apolipoprotein A-I levels, with positive correlation between these two parameters. TC/HDL-c ratio showed significant difference among the groups. Positive correlation was found between Lp(a) and LDL-c, and negative one, between the ankle-arm index and LP(a). CONCLUSION: As to the lipid parameters studied, significant statistical differences were found between HDL-c and apolipoprotein A-I plasma levels only. For Lp(a) parameter, higher plasma levels were observed in PAOD and PAOD + DM2, which have also shown concomitant and significant HDL-c reduction.

Níveis plasmáticos elevados de lipoproteína(a) correlacionados com a gravidade da doença arterial coronariana em pacientes submetidos à angiografia

OBJETIVO: Determinar os niveis plasmaticos de lipoproteina(a) e perfil lipidico de um grupo de individuos submetidos a angiografia coronariana, buscando estabelecer a possivel correlacao entre estes parâmetros e a gravidade da doenca coronariana. METODOS: Niveis plasmaticos de colesterol total, HDLC, LDLC, triglicerides, lipoproteina(a), apolipoproteinas A-I e B foram medidos em amostras de sangue de 17 individuos com ausencia de ateromatose nas coronarias (controles), 12 individuos apresentando ateromatose leve/moderada e 28 individuos apresentando ateromatose grave. RESULTADOS: Nao foram encontradas diferencas estatisticamente significativas entre as medias dos tres grupos para os parâmetros avaliados, exceto para os niveis plasmaticos de lipoproteina(a) que apresentaram diferencas significativas entre as medias dos grupos controle, ateromatose leve/moderada e ateromatose grave (p<0,001). CONCLUSAO: As medias obtidas nos tres grupos para Lp(a) sinalizam um aumento progressivo nos niveis plasmaticos deste parâmetro, de acordo com a gravidade da ateromatose coronariana. Estes achados sugerem a necessidade de estudos adicionais, visando obter suficiente evidencia para a introducao rotineira da avaliacao dos niveis de Lp(a) em laboratorios clinicos, no monitoramento de pacientes apresentando risco para doenca arterial coronariana (DAC).

Apo B/Apo A-I ratio in central and peripheral arterial diseases

BACKGROUND The apo B/apo A-I ratio represents the balance between atherogenic particles, rich in apo B, and the antiatherogenic ones, apo A-I rich. This study investigated the association between atherosclerotic diseases in different anatomical sites and apo B/apo A-I ratio. METHODS Lipids, lipoproteins, and apolipoproteins A-I and B were assessed in 30 subjects with coronary artery disease (CAD), 26 with ischemic stroke (IS), 30 with peripheral arterial obstructive disease (PAOD), and 38 healthy subjects (controls). RESULTS HDLc and Apo A-I were significantly lower in PAOD and CAD groups, respectively, than in other groups. Significantly higher levels of triglycerides were observed for CAD and PAOD groups than for controls. Apo B was significantly higher in IS group than in control and PAOD groups. The apo B/apo A-I ratio showed significantly higher in CAD and IS groups when compared to control and PAOD groups (p < 0.001). CONCLUSION The apo B/apo A-I ratio was important for identifying an increased trend for coronary and cerebral atherosclerosis. In spite of the increased trend for apo B/apo A-I ratio in IS and CAD groups, the studied variables cannot be considered in an isolated way, given as those parameters were analyzed together by a binary logistic regression, no association has been demonstrated.

Creatinine and cytokines plasma levels related to HLA compatibility in kidney transplant patients

Introduction:The success of kidney transplantation depends on prevention of organ rejection by the recipient’s immune system, which recognizes alloantigens present in transplanted tissue. Human leukocyte antigen (HLA) typing is one of the tests used in pre-renal transplantation and represents one of the most important factors for a successful procedure.Objective:The present study evaluated creatinine and cytokines plasma levels in kidney transplant patients according to pre-transplant HLA typing.Methods:We assessed 40 renal transplanted patients selected in two transplant centers in Belo Horizonte (MG).Results:Patients were distributed into three groups according to HLA compatibility and, through statistical analysis, the group with more than three matches (H3) was found to have significantly lower post-transplant creatinine levels, compared to groups with three or fewer matches (H2 and H1, respectively). The median plasma levels of cytokines interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin 10 (IL-10) were evaluated according to the number of matches. Pro-inflammatory cytokines (IL-6 and TNF-α) were significantly higher in groups with lower HLA compatibility. On the other hand, the regulatory cytokine IL-10 had significantly higher plasma levels in the group with greater compatibility between donor and recipient.Conclusion:These findings allow us to infer that pre-transplant HLA typing of donors and recipients can influence post-transplant renal graft function and may contribute to the development and choice of new treatment strategies.

Hemostatic Parameters according to Renal Function and Time after Transplantation in Brazilian Renal Transplanted Patients

Kidney transplantation is the key for patients with end-stage renal disease, improving quality of life and longer survival. However, kidney transplant triggers an intense inflammatory response and alters the hemostatic system, but the pathophysiological mechanisms of these changes are not completely understood. The aim of this cross-sectional cohort study was to investigate hemostatic biomarkers in Brazilian renal transplanted patients according to renal function and time after transplantation. A total of 159 renal transplanted patients were enrolled and D-Dimer (D-Di), Thrombomodulin (TM), von Willebrand Factor (VWF), and ADAMTS13 plasma levels were assessed by ELISA. An increase of D-Di was observed in patients with higher levels of creatinine. ADAMTS13 levels were associated with creatinine plasma levels and D-Di levels with Glomerular Filtration Rate. These results suggested that D-Di and ADAMTS13 can be promising markers to estimate renal function. ADAMTS13 should be investigated throughout the posttransplant time to clarify the participation of this enzyme in glomerular filtration and acceptance or rejection of the graft in Brazilian transplanted patients.

Regulatory and Pro-Inflammatory Cytokines in Brazilian Living-Related Renal Transplant Recipients According to Creatinine Plasma Levels

The maintenance of stable graft function in renal transplanted recipients (RTR) is a challenge for healthcare staff. The ideal biomarkers must have significant predictive values to monitor the intricate renal function response triggered after renal transplantation. The main purpose in this study was to evaluate the regulatory and pro‐inflammatory cytokines as biomarkers of allograft function in living‐related renal transplant patients.

Apolipoprotein E and PAI-1 gene polymorphisms and no association with arterial ischemic stroke and peripheral arterial disease manifestations

Introduction: Arterial thrombosis is considered a multifactorial disease, resulting from the interaction of genetic and acquired risk factors. Objectives: The aim of this study was to investigate the presence of the polymorphism in inhibitor of plasminogen activator type 1 (PAI-1) and apolipoprotein E (ApoE) genes and its interactions with PAI-1 levels and lipids and apolipoprotein profiles, respectively, as well as the frequencies of these polymorphisms and their association with thrombosis. Methods: Ninety-seven patients [48 with arterial ischemic stroke (IS) and 49 with peripheral arterial disease (PAD)], treated at the hematology medical service were included in this study. Polymorphisms were also investigated in 201 control subjects. Polymorphisms were investigated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: For the PAI-1 polymorphism, there were 54.2% heterozygous (HT) genotypes and 12.5% homozygous (HM) genotypes in the patients’ group, and 52.7% HT genotypes and 21.3% HM genotypes in the controls. For the ApoE polymorphism, there were 56.3% (ε3ε3), 6.3% (ε4ε4), 8.3% (ε2ε3), 4.2% (ε2ε4) and 24.9% (ε3ε4) in the patients, and 61.2% (ε3ε3), 4.5% (ε4ε4), 8% (ε2ε3), 4.5% (ε2ε4) and 21.8% (ε3ε4) in the controls. Conclusion: No significant difference was observed by comparing patients and controls. In this study, no association was found between the presence of the evaluated polymorphisms and the occurrence of thrombotic events.