Circulating microRNAs in Cardiovascular Diseases.

Cardiovascular Diseases (CD) are currently one of the most common causes of death. Because heart related deaths occur on such an enormous scale this phenomenon is referred to as an epidemic. Chronic and acute injury of the heart could be an effect of cardiac remodeling, which is a result of molecular, cellular and interstitial changes, influenced by hemodynamic load or neurohormonal activation (Cohn et al., 2000). These small deviations in cardiac activity and morphology may lead to an enormous negative effect. Despite a significant progress, knowledge of standard risk factors for cardiovascular diseases has become less and less effective, which is why predicting and seeking an appropriate treatment is very challenging. As a result, there is a growing interest in finding new markers of the CD. MicroRNAs (miRNAs), are short, non-coding RNAs responsible for regulation of gene expression at the post-transcriptional level. Among them that have the greatest potential are microRNA molecules that circulate in the blood plasma or serum, that are related to direct activation of signaling pathways, implicated in the aging process and thus for the development of cardiovascular disease. This paper is a summary of the current state of knowledge on miRNAs, their biogenesis and potential role as biomarkers to diagnose heart disease.

Effects of L-arginine and NG-nitro L-arginine methyl ester (L-NAME) on ischemia/reperfusion injury of skeletal muscle, small and large intestines.

This study analyzed the effects of L-arginine and non-specific nitric oxide (NO) synthase blocker (L-NAME) on structural and metabolic changes in experimental ischemia/reperfusion injury in the rat. Histopathological evaluation of rat tissues after reperfusion was also performed. The animals were divided into four groups: [1] nonischemic control, [2] ischemia 4 hrs/repefusion 30, 60, 120 min, [3] ischemia/reperfusion after L-arginine administration, [4] ischemia/reperfusion, after L-arginine, and L-NAME. L-arginine (500 mg/kg) and L-NAME (75 micromol/rat/day) were administrated orally for 5 days before experiment. Concentrations of free radicals, CD-62P, CD-54 and malonyl dialdehyde (MDA) in tissues, and MDA and NO levels in sera were determined. Free radical levels significantly increased in reperfused skeletal muscle, small and large intestines. In large bowel, reperfusion increased MDA levels and evoked a rise of endotoxin level while NO levels decreased. Histological studies showed an increase in the number of lymphocytes in both intestines. Administration of L-arginine reduced leukocyte adherence associated with ischemia-repefusion injury, decreased the levels of free radicals and MDA in the examined tissues, and inhibited the release of endotoxins into blood. L-arginine-treated animals showed higher serum NO levels and reduced leukocyte bowel infiltration. Concomitant L-NAME administration reduced serum NO and tissue free radical [corrected] levels, but did not affect intestinal leukocyte infiltration. L-arginine could ameliorate intestinal ischemia/reperfusion injury and constitute a possible protective mechanism by decreasing neutrophil-endothelial interactions, stimulating free radical scavenging and reducing lipid peroxidation.

Neopterin as a prognostic marker in patients with chronic heart failure.

BACKGROUND: The study aimed at evaluating neopterin concentration in relation to heart failure etiology and determining basal neopterin concentration in relation to the clinical state of patients after 12 months of standard treatment. MATERIAL/METHODS: The examined group was composed of 47 patients with NYHA class II and III heart failure and 20 healthy volunteers. Neopterin concentration in blood serum was determined with a radioimmunological assay. Twelve months after the patients had left the hospital, their quality of life and clinical symptoms of heart failure were evaluated. RESULTS: Statistically significantly higher basal concentrations of neopterin in the group of patients with CHF than in the control group (p<0.001) were noted. A higher concentration was found in NYHA class III than in NYHA class II CHF patients (p<0.001). No difference in relation to heart failure etiology was detected. The basal neopterin concentration determined patients' clinical status after the 12-month standard chronic heart failure treatment. CONCLUSIONS: In the 12-month observation, a relationship was detected between neopterin concentration and heart failure progression, which may point to neopterin as a marker of heart failure progression.

Evaluation of the antihypertensive effect of L-arginine supplementation in patients with mild hypertension assessed with ambulatory blood pressure monitoring.

BACKGROUND: Arterial hypertension is one of the most important cardiovascular risk factors, featuring the unsatisfactory efficacy of current therapies. The cardiovascular disease paradigm which assumes a crucial role of the endothelial phenotype in shaping the state of the circulatory system has become increasingly dominant and endothelial dysfunction should be treated as avidly as the diseases of other organs. The most valued current anti-hypertensive therapies exert a positive influence on the endothelium due to their pleiotropic effects, but the search for new effective strategies aimed at improving endothelial function is underway. L-arginine trials are part of this quest. The few L-arginine studies in hypertension have brought inconclusive results. The aim of this study was to evaluate the anti-hypertensive efficacy and safety profile of L- arginine during four weeks of oral supplementation to healthy subjects and patients diagnosed with primary mild hypertension. MATERIAL/METHODS: The study was completed by 54 participants. Ambulatory blood pressure monitoring (ABPM) was used to allot patients to either a healthy control group (19 subjects) or the hypertensive treatment group (35 patients). Later the patients were randomized to either L-arginine (2 or 4 g three times daily or placebo. All participants underwent physical examination and had all basic lab tests and ABPM performed. RESULTS: Blood pressure (both systolic and diastolic) by ABPM showed statistically significant lowering after 4 weeks of L-arginine supplementation only in the subgroup of patients treated with 12 g of L-arginine daily, with a stronger hypotensive effect observed during the day. CONCLUSIONS: The present findings demonstrate a strong association between L-arginine supplementation and blood pressure reduction.

Global DNA methylation changes in blood of patients with essential hypertension.

BACKGROUND: Hypertension is a common disease of the cardiovascular system and one of the main causes of mortality in the world. Its etiopathogenesis and molecular mechanisms are unknown. Epigenetic changes may play a role in its development. Therefore the level of 5-methylcytosine (5mC), a well-known epigenetic marker, was analyzed in DNA from the blood of essential hypertension patients. MATERIAL/METHODS: TLC chromatographic analysis of the DNA nucleotide composition was used to determine 5mC levels in blood DNA samples from 60 patients suffering from essential hypertension (30 with stage 1 and 30 with stage 2 hypertension) and 30 control subjects. RESULTS: The mean levels of 5mC were 1.80 + or - 0.69 in the healthy subjects, 1.14 + or - 0.48 in all the patients with essential hypertension, 1.29 + or - 0.50 in those with stage 1, and 0.99 + or - 0.42 in those with stage 2 of hypertension. Statistically significant differences in 5mC amount in DNA were observed between the control group and the whole patient group, the control group and each subgroup of patients, and the groups of patients with stage 1 and stage 2 of hypertension. The level of 5mC in the DNA of the essential hypertension patients was independent of clinical and biochemical factors. CONCLUSIONS: The level of 5mC in the DNA of patients suffering from essential hypertension is lower than in healthy people and depends of the progression of hypertension.

Influence of selected angiotensin-converting enzyme inhibitors on alloxan-induced diabetic cataract in rabbits.

BACKGROUND: Hyperglycemia enhances cataractogenesis. Elevated glucose level is commonly accompanied by arterial hypertension, for which angiotensin-converting enzyme (ACE) inhibitors (ACEIs) are a widely used intervention. ACE inhibitors exert some endothelial pleiotropic actions and can beneficially modulate glucose control and some other metabolic pathways. The purpose of this study was to evaluate the effect of ACEIs on cataract formation in experimental alloxan-induced diabetes in rabbits and assess the role of the reactive function group of the ACEIs in this process. MATERIAL/METHODS: Two study and two control groups of rabbits were examined. In the study groups and in one of the control groups, diabetes was induced by alloxan. The study groups were assigned to receive captopril or enalapril for six months; the controls received distilled water. Glucose concentration was monitored with a glucometer. A biomicroscope and an ophthalmoscope were used to evaluate lens opacity and cataractogenesis. RESULTS: Six-month administration of ACEI to rabbis resulted in a delay of diabetic cataractogenesis. The rate of cataract formation was significantly lower in the group treated with captopril than in the enalapril group. A difference in morphology of lens opacity formation between the two study groups was observed. CONCLUSIONS: ACEIs delay diabetic cataractogenesis in an experimental animal model. The ACEI functional groups have different influences on the pattern and rate of lens opacity.

[The pharmacokinetic of drugs in elderly patients]. / Farmakokinetyka leków w wieku podeszlym.

The use of pharmacotherapy in the elderly requires caution because of increasing with age drug sensitivity and risk of dangerous adverse effects. The process of ageing induce alteration in pharmacokinetics of drugs. Modifications affect practically each pharmacokinetic phase. Processes of distribution and, first of all, drug elimination are the most essential for clinical practice.

[The evaluation of level of epigenetic indicator--5-methylcytosine in smoking and non-smoking patients with mild essential hypertension]. / Ocena poziomu wskaznika epigenetycznego--5-metylocytozyny u chorych z pierwotnym lagodnym nadcisnieniem tetniczym palacych i niepalacych papierosy.

5-methylcytosine (m5C, 5mC) is a nucleotide occurring naturally in genomic DNA and play an important role in regulation of genes expression. Methylation of cytosine in DNA is an epigenetic modification and different intrinsic and extrinsic factors can influence on its level. For example, it is subject to modification and/or degradation by the free radicals which are commonly present in environment of human, among others the cigarette smoke. The reactions of m5C with free radicals lead to origination of many products which effect is decrease of level of m5C in DNA (hypomethylation) and excessive expression of genes inducing development of different diseases, especially cardiovascular system diseases. The aim of the study was statement if exist differences of level of 5-methylcytosine in DNA between smoking and non-smoking patients suffering from mild essential hypertension. The study group was composed of 30 patients suffering from mild essential hypertension (21 females and 40 males) aged from 18 to 55 years (32.4+/-10.3 years). The group of smoker was composed of 13 patients (5 females and 8 males) and the group of non-smokers was composed of 17 patients (7 females and 10 males). 3-5 ml of blood was sampled on EDTA and then thin-layer chromatography analysis of 5-methylcytosine level in DNA after previous enzymatic hydrolysis of DNA and radioactive phosphorus labeling [32p] was performed. The mean level of 5-methylcytosine (m5C) were 1.30+/-0.56 [%] in non-smoking patients, and 1.28+/-0.42 [%] in smoking patients suffering from mild essential hypertension. There is no significant statistically differences between non-smoking and smoking patients (p>0.4). In the study the following conclusion was drawn: the level of m5C in DNA of patients suffering from mild essential hypertension in the study is independent of smoking (p>0.4) in patients with mild essential hypertension. However it supposes, out of regard for theoretic datum suggestive such influence, the study should be performed in more frequent group of patients.