Samia Abd El-Moneim Ebied, Nadia Aly Sadek, Nadia El-Sayed Zaki, Samir Ali Abd El- Kaream and Heba Khafagui Ahmed El Kashif
The renin-angiotensin system (RAS) is a bioenzymic cascade that plays an integral role in cardiovascular homoeostasis by influencing vascular tone, fluid and electrolyte balance and the sympathetic nervous system. RAS was viewed as a circulating endocrine system, whereby renin released from the juxtaglomerular cells of the kidney cleaves the liver-derived macroglobulin precursor angio-tensinogen, to produce the inactive decapeptide angiotensin I, which is then converted to the active octapeptide Ang II by angiotensin converting enzyme (ACE) within the pulmonary. There is increasing evidence that Ang II, a major regulator of blood pressure and cardiovascular homeostasis, is involved in the regulation of cell proliferation, angiogenesis, inflammation and tissue remodeling, which suggests that this peptide might also play a role in cancer. Ang II is the main effector of the RAS and it alternatively binds to either Ang II T1R or Ang II T2R. The Ang II T1R and Ang II T2R can act as antagonists, and mediate effects on cell migration and proliferation of metastatic cancer cells and hemopoietic stem-progenitor cells. Components of the RAS are frequently differentially expressed in various cancers in comparison with their corresponding non- malignant tissue. Yet, the RAS has not been fully elucidated in patients with acute leukemia. Objective: The aim of the present work was to study serum level of Angiotensin II receptor type 1 and the soluble angiotensin converting enzyme (CD143) in patients with acute leukemia in order to extrapolate their possible prognostic value.
Subjects and Methods
The present study included 20 healthy volunteers clinically free from hypertension or sarcoidosis, 20 patients of newly diagnosed AML and 20 patients of newly diagnosed ALL. Blood samples were collected from all subjects and the level of serum ACE and serum Ang IIT1R were measured by enzyme linked immunossorbent assay.
The activity of ACE (U/L) and the concentration of Ang IIT1R (U/L) in patients groups with either AML or ALL before therapy were significantly higher than in control group. After therapy, the activity of the enzyme and its receptor concentration in both groups of patients were significantly decreased but still significantly higher than in normal control subjects.
Estimating the serum level of ACE and soluble Ang IIT1R is of informative diagnostic and prognostic value. Estimation serum level of ACE and Ang IIT1R levels in patients with either AML or ALL is of value in deciding the treatment protocol.
Glomerular disease is the most common cause of endstage renal disease (ESRD), accounting for almost two thirds of cases. In glomerular disease, alterations of po-docytes are of particular importance. Podocyte loss represents a central mediator of glomerular sclerosis. Toxic, genetic, immune, infectious, oxidant, metabolic, hemody-namic, and other mechanisms can all target the podo-cytes. These mechanisms provide new insight into the unique dynamic microenvironment that each individual podocyte inhabits and how it can turn hostile to survival. At the same time, they raise new therapeutic challenges to preserve glomerular function by containing podocyte injury and limiting its spread, both in podo-cytopathies and in other progressive glomerular diseases. Treatment strategies should aim at enhancing podocyte survival. The renin-angiotensin axis blockade, apart from its antifibrotic and intraglomerular hemodynamic effects, has an important role in preventing podocyte loss. However, only long-term observational studies can clarify if many patients will benefit from podocyte-targeted treatment such as abatacept or similar agents.
Zbigniew Heleniak, Zbigniew Zdrojewski, Piotr Wisniewski, Leszek Bieniaszewski, Boleslaw Rutkowski and Alicja Debska-Slizien
Endothelial dysfunction could be related to the limited availability of nitric oxide (NO). NO is synthesized with the participation of an NO synthase whose activity is inhibited by asymmetric dimethylarginine (ADMA). The synthesis of ADMA is exacerbated by oxidative stress, and several studies have shown the efficacy of drugs acting on the renin-angiotensin-aldosterone system (RAAS) (converting enzyme inhibitors and angiotensin II receptor antagonists) in reducing the level of ADMA. The probable mechanism of drug action is a reduction of oxidative stress through a decrease of angiotensin II formation. The aim of this study was to assess the influence of RAAS blockers on the plasma concentration of ADMA in patients with chronic glomerulonephritis (ChGN). The study included 37 patients, placed into group A and group B, depending on the treatment. Both groups were treated with RAAS blockers. In group B, immunosuppressive drugs were additionally administered. The control visits were at the 0, 6 and 12 months of observation. In both the studied groups (A+B), a significant reduction of ADMA (0.77 vs 0.4 μmol/l; p<0.05) was noticed. In patients suffering from ChGN, the use of RAAS blockers resulted in a significant decrease of plasma ADMA concentration, independently of immunosupressive treatment.
Algimantas Paulauskas, Asta Danileviciutė, Tadas Povilaitis and Jonas Poderis
Genetic Variability Associated with Angiotensin Converting Enzyme (ACE) Gene Polymorphism in Sportsmen Pursuing Different Sports
The purpose of the study was to determine angiotensin converting enzyme (ACE) gene polymorphisms in sportsmen and sedentary individuals and to evaluate the differences in frequencies of ACE genotype and allele distribution among sportsmen who are involved in different sports. In this study 255 participants were analysed: 116 sedentary individuals and 139 sportsmen. Sportsmen were differentiated into separate groups according to various sports: endurance, strength requiring, cyclic and acyclic sports. DNA was purified from peripheral blood with a DNA purification kit "Fermentas". ACE gene polymorphic region was amplified by polymerase chain reaction (PCR). DNA electrophoresis was used to separate DNA fragments by size. Bands were visualised under ultra violet (UV) light. The frequency of D allele was higher than I allele in sedentary individuals; the sportsmen had higher frequency of I allele. The X2 test showed allele selection in sedentary individuals. Frequency of the I allele among the individuals who belong to endurance requiring sports was higher than was the D allele, while among the individuals who belong to sports requiring strength, the D and I allele frequences were equal. Differences in the individuals who belong to acyclic sports group were not significant — the frequency of I allele was much higher than D in the cyclic sports group. D allele frequency was twice higher than I allele among wrestlers.
Adeolu A. Adedapo, Temidayo O. Omobowale, Ademola A. Oyagbemi and Momoh A. Yakubu
All over the world, cardiovascular diseases are a risk factor for poor health and early death with predisposing factors to include age, gender, tobacco use, physical inactivity, excessive alcohol consumption, unhealthy diet, obesity, family history of cardiovascular disease, hypertension, diabetes mellitus, hyperlipidemia, psychosocial factors, poverty and low educational status, and air pollution. It is envisaged that herbal products that can stem this trend would be of great benefit. Garcinia kola (GK), also known as bitter kola is one of such plants. Generally used as a social snack and offered to guests in some cultural settings, bitter kola has been indicated in the treatment of laryngitis, general inflammation, bronchitis, viral infections and diabetes. In this study, the effects of methanol seed extract of Garcinia kola on the proliferation of Vascular Smooth Muscle Cells (VSMCs) in cell culture by Angiotensin II (Ang II) and LPS-induced NO production were carried out. Confluent VSMCs were exposed to GK (25, 50 and 100 μg/ml) before or after treatment with lipopolyssacharide (100μg/ml), and Angiotensin II (10−8-10−6M). Cellular proliferation was determined by MTT assay and NO production by Griess assay. Treatment with Angiotensin II (10−8, 10−6) or LPS significantly enhanced proliferation of VSM cells while LPS significantly increased nitric oxide (NO) production. Treatment with GK (25, 50 & 100 μg/ml) attenuated VSM cell proliferation. The results indicate that GK has potential to inhibit mitogen activated vascular cell growth and possibly inhibit inflammatory responses to LPS. Thus GK may be useful in condition that is characterized by cellular proliferation and inflammatory responses.
Micro RNAs (miRNAs) are small regulatory molecules of increasing biologists’ interest. miRNAs, unlikely mRNA, do not encode proteins. It is a class of small double stranded RNA molecules that via their seed sequence interact with mRNA and inhibit its expression. It has been estimated that 30% of human gene expression is regulated by miRNAs. One miRNA usually targets several mRNAs and one mRNA can be regulated by several miRNAs. miRNA biogenesis is realized by key enzymes, Drosha and Dicer. miRNA/mRNA interaction depends on binding to RNA-induced silencing complex. Today, complete commercially available methodical proposals for miRNA investigation are available. There are techniques allowing the identification of new miRNAs and new miRNA targets, validation of predicted targets, measurement of miRNAs and their precursor levels, and validation of physiological role of miRNAs under in vitro and in vivo conditions. miRNAs have been shown to influence gene expression in several endocrine glands, including pancreas, ovary, testes, hypothalamus, and pituitary.
Anca Chiriac, Piotr Brzezinski, Mircea Betiu and Liliana Foia
Angiotensin-converting enzyme inhibitors (ACEI) are widely used drugs nowadays in treating patients diagnosed with cardiovascular disorders. We present two consecutive cases of acquired angioedema caused by the administration of enalapril and lisinopril in patients with indication for ACE-inhibitors therapy. Rigorous follow-up of side effects of ACEI is required, due to these possible life-threatening adverse reactions.
Adipose tissue expresses all the renin-angiotensin system (RAS) components that play an important role in the adipogenesis, lipid and glucose metabolism regulation in an auto/paracrine manner. The classical RAS has been found to be over-activated during the adipose tissue enlargement, thus elevated generation of angiotensin II (Ang II) may contribute to the obesity pathogenesis. The contemporary view on the RAS has become more complex with the discovery of alternative pathways, including angiotensin-converting enzyme 2 (ACE2)/angiotensin (Ang)-(1-7)/Mas receptor, (pro)renin receptor, as well as angiotensin IV(Ang IV)/AT4 receptor. Ang-(1-7) via Mas receptor counteracts with most of the deleterious effects of the Ang II-mediated by AT1 receptor implying its beneficial role in the glucose and lipid metabolism, oxidative stress, inflammation, and insulin resistance. Pro(renin) receptor may play a role (at least partial) in the pathogenesis of the obesity by increasing the local production of Ang II in adipose tissue as well as triggering signal transduction independently of Ang II. In this review, modulation of alternative RAS pathways in adipose tissue during obesity is discussed and the involvement of Ang-(1-7), (pro)renin and AT4 receptors in the regulation of adipose tissue homeostasis and insulin resistance is summarized.
Cholangitis of Pancreatitis? Does the Angiotensin-Converting Enzyme Genotype Favor Either?
Acute cholangitis and pancreatitis are serious complications of gallstones, with considerable morbidity and mortality. Angiotensin-converting enzyme (ACE) is an exopeptidase that is important in regulating blood pressure, metabolizing bradykinin and in maintaining an inflammatory response. To determine whether the ACE genotype determines occurrence of cholangitis or pancreatitis we examined ACE I/D genotypes in 31 patients who had cholangitis, 44 patients with biliary pancreatitis and 157 healthy individuals. The patients had been hospitalized at the Department and Intensive Care Faculty of Medicine, Ege University, Izmir, Turkey. The patients were recalled 4 years later and their prognosis was evaluated. The ACE II genotype was found at a higher frequency in the cholangitis and biliary pancreatitis patients when compared with the healthy subjects (p <0.05). There was no significant difference between cholangitis and biliary pancreatitis cases regarding the genotype and allele distribution (p >0.05). Recurrence of infection occurred more frequently in the patients with the DD genotype, although it was not significant according to the first assessment (p >0.05). The ACE gene polymorphism did not seem to favor development of either cholangitis or pancreatitis.