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ABSTRACT: MicroRNAs (miRNAs) are a family of small, noncoding RNAs that repress gene expression at the post-transcriptional level. Over 700 miRNAs have been identified in the human genome, of which 20% to 30% regulate human protein-coding genes. Functional in vitro studies have shown that miRNAs are critical for endothelial cell gene expression and function. miRNAs were found in atherosclerosis, cardiac hypertrophy, arterial hypertension, coronary artery disease, diabetes, and inflammatory diseases. We review the current knowledge about the role of miRNAs in endothelial cells with emphasis on the regulation of cellular senescence, angiogenesis, and vascular inflammation. It has been shown that miR-34a, miR-217, miR-200, miR-146c, and miR-181a are responsible for the regulation of cell stress and proliferation processes. Proangiogenic factors include miR-130a, miR-210, miR-424, miR-17-92, miR-27-b, let-7f, and miR-217, while miR-221 and miR-222 have antiangiogenic properties. Other known miRNAs, including miR-31, miR17-3p, miR-155, miR-221, miR-222, and miR-126, are important factors in the regulation of vascular inflammation. Studies show that miRNA expression analysis can be used in the diagnosis and treatment of various diseases; however, additional research is needed before it is used in routine clinical setting.
Polskie archiwum medycyny wewnȩtrznej 09/2011; 121(10):361-6. · 1.37 Impact Factor
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ABSTRACT: Humanin (HN) is a newly discovered 24-amino acid peptide, which may suppress neuronal cell death. HN cDNA includes the open reading frame (HN-ORF) of 75 bases, located 950 bases downstream of the 5' end of the HN cDNA. It was demonstrated that HN cDNA is 99% identical with mitochondrial DNA (mtDNA) sequence. HN homologues have been identified as expressed sequence tags (ESTs) in rat and nematode. Certain regions homologous to the HN cDNA exist on human chromosomes. HN forms homodimers and multimers and this seems to be essential for the peptide functions. HN acts as a ligand for formyl peptide receptor-like 1 (FPRL1) and 2 (FPRL2). It was demonstrated that HN plays a protective role by an antiapoptotic activity interfering with Bax activation, and suppressing Bax-dependent apoptosis. HN is also shown to suppress the c-Jun N-terminal kinase (JNK) and ASK/JNK-mediated neuronal cell death. Several studies also confirm that HN could be important in prevention of angiopathy-associated Alzheimer's disease dementia, diseases related to mitochondrial dysfunction (MELAS), and other types of beta-amyloid accumulation associated neurodegeneration. A very recent study demonstrated a pluripotent cytoprotective effect and mechanisms of HNs in cells other than from the CNS, such as germ cells, or panreatic b-cells, and potent physiological consequences that result from HN interaction with IGFBP3 and STAT3. The in vivo studies suggest that humanin may protect against cognitive impairment, also due to ischemia/reperfusion injury.
Przegla̧d lekarski 01/2011; 68(7):372-7.
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ABSTRACT: Adiponectin, a protein secreted by adipose tissue but present at low levels in obesity, is now widely recognized as a key determinant of insulin sensitivity and of protection against obesity-associated metabolic syndrome. The adiponectin gene is very polymorphic and several of its variants contribute to adiponectin level, function and are associated with metabolic syndrome phenotypes. The results differ ethnically. The association of identified variants with obesity and its consequences, type 2 diabetes and cardiovascular disease is reviewed. This data may enable patients at greater risk of the adverse effects of obesity to be identified and, as such, benefit from more targeted therapy and prevention.
Przegla̧d lekarski 02/2009; 66(5):257-62.
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ABSTRACT: Nutrigenomics is a promising multidisciplinary field that focus on studying the interactions between nutritional factors, genetic factors and health outcomes. Its goal is to achieve more efficient individual dietary intervention strategies aimed at preventing disease, improving quality of life and achieving healthy aging. Somehow, nutrigenomics has been used for decades in certain rare monogenic diseases such as phenylketonuria. It has the potential to provide a basis for personalized dietary recommendations based on the individual's genetic makeup in order to prevent common multifactorial disorders (such as metabolic syndrome) decades before their clinical manifestation. Preliminary results regarding gene-diet interactions in many diseases are for the most part inconclusive because of the limitations of current designs. Success in this area will require the integration of various disciplines (e.g. biotechnology, medicine, biology, economics) and will require investigators to work on ethnic groups. This knowledge should lead to successful dietary recommendations partly based on genetic factors that may help to reduce disease risk more efficiently than the current universal recommendations based mainly on epidemiological studies. We discuss nutrigenomic issues and show examples for this new, with a wide research area, field of science.
Przegla̧d lekarski 02/2005; 62(4):245-52.
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ABSTRACT: Adiponectin (also called AdipoQ, gelatin-binding protein 28, Acrp30) is a novel adipocytokine with important metabolic effects. It is physiologically released from adipose tissue and circulates in serum as a hexamer and larger multimeric structure of high molecular weight. Serum level of the protein correlates with systemic insulin sensitivity. Recently adiponectin receptors AdipoR1 and AdipoR2 have been discovered by expression cloning. AdipoR1 is abundantly expressed in skeletal muscles, whereas AdipoR2 is predominantly expressed in the liver. Marked expression of mRNA for AdipoR1 and AdipoR2 has been lately reported in pancreatic beta cells. Both of the receptors activate AMPK and PPAR alpha metabolic pathways leading to an increase in fatty acid oxidation, glucose uptake and a decreased rate of gluconeogenesis, thus enhancing insulin sensitivity. Moreover effects of adiponectin mimic many metabolic actions of insulin such as augmenting blood flow and glucose disposal in NO-dependent manner. The precise mechanism of regulation of plasma adiponectin level is unknown. Recently the mechanism of transcriptional activation of adiponectin gene via PPAR gamma was described. Its level seems to be decreased by TNFalfa and beta-adrenergic agonists. Furthermore there is increasing evidence that some genetic variants in the adiponectin gene may be associated with its ethnical differences in level as well as its likely clinical consequences. Hipoadiponectynemia is associated with obesity, metabolic syndrome, diabetes type 2, cardiovascular disease, lipodystrophy in AIDS. In patients with chronic renal failure, anorexia nervosa plasma adlponectin level is increased. Weight loss and therapy with thlazolidinediones are proved to enhance endogenous adlponectin production in humans. In summary, the ability of adiponectin to increase insulin sensitivity in conjunction with its anti-inflammatory and antiatherogenic properties have made this novel adipocytokine a promising therapeutic tool for the future, especially in individuals with low plasma levels of adiponectin.
Przegla̧d lekarski 02/2004; 61(2):109-14.
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ABSTRACT: Previous studies have suggested that genetic variation in the beta2 (b2-AR) and beta3 (b3-AR) adrenergic receptor genes are associated with obesity and insulin resistance. The aim of this study was to evaluate the influence of beta2 (Gln27>Glu) and beta3 (Trp64>Arg) adrenoreceptor gene polymorphisms on BMI and carbohydrate-lipid metabolism in Polish obese families.
122 persons (84 women, 38 men) from 40 obese families (BMI 33.5I7.7) were included. PCR-RFLP analysis of genotype was plotted against anthropometric parameters and the results of glucose and lipid oral tolerance tests. Venous blood samples were analysed for concentrations of glucose, insulin, free fatty acids, triglycerides, total cholesterol, HDL-chol, LDL-chol, leptin, and vWF.
We found 39% Glu27 with 8% Arg64 allele frequencies. The blood glucose and insulin concentration during OGTT and blood FFA and TG level during OLTT was lower in patients with the Glu/Glu b2-AR polymorphism than Glu/Gln and Gln/Gln. In the obese patients the same effect was observed; however, the percent of fat body mass, leptin concentration, and BMI was higher in this group. Patients with the Trp/Trp polymorphism in the b3-AR gene were characterized by higher glucose and insulin concentration during OGTT and higher blood concentration of FFA and TG during OLTT. These results were independent of BMI value.
The b2-AR 27Glu and b3-AR 64Arg alleles have a protective effect against metabolic disorders in obese families from southern Poland.
Medical science monitor: international medical journal of experimental and clinical research 06/2003; 9(6):CR225-34. · 1.70 Impact Factor
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ABSTRACT: Tumour necrosis factor alpha (TNF-alpha), acting as a modulator of gene expression in adipocytes, has been linked to the development of insulin resistance and obesity. The aim of this study was to investigate whether the A/G variation at position -308 in the TNF-alpha promoter influences the body weight, insulin resistance, and postprandial lipaemia in Polish Caucasians. One hundred twenty one subjects, 38 men and 83 women, representing 40 obese families, were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). TNF-1 (GG) and TNF-2 (GA and AA) allele carriers were compared with respect to body mass index, fat/lean body mass composition, waist-to-hip ratio, as well as fasting lipids, glucose, leptin, and insulin fasting, and during the oral glucose tolerance test (4 points within 2 hours) and oral lipid tolerance test (OLTT; 5 points within 8 hours). The insulin sensitivity indices HOMA-IR (homeostasis model assessment of insulin resistance), ISI-COMP (whole body insulin sensitivity index), ISI-HOMA (hepatic insulin sensitivity), and DELTA (early secretory response to an oral glucose load) were calculated. We detected 64 GG, 56 GA, and 1 AA genotypes. Significant increases of insulin resistance parameters in obese female TNF-2 allele carriers were observed (significantly increased HOMA-IR and decreased ISI-HOMA, ISI-composite). The male TNF-2 carriers were characterised by significantly increased levels of triglyceride and free fatty acids during OLTT as well as fasting glucose. The A/G variation at position -308 in the promoter region of the TNF-alpha gene could be an important genetic factor predisposing to insulin resistance in obese women and increased levels of glucose, triglyceride, and free fatty acids in men.
Clinical Chemistry and Laboratory Medicine 05/2003; 41(4):501-10. · 2.15 Impact Factor
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ABSTRACT: Humanin (HN) is a newly discovered 24-amino acid peptide, which may suppress neuronal cell death. HN cDNA includes an open reading frame (HN-ORF) of 75 bases located 950 bases downstream of the 5' end of the HN cDNA. It has been demonstrated that HN cDNA is 99% identical to the mitochondrial DNA (mtDNA) sequence. HN homologs have been identified as expressed sequence tags (ESTs) in both rats and nematodes. Certain regions that are homologous to the HN cDNA exist on human chromosomes. HN forms homodimers and multimers and this action seems to be essential for peptide function. HN acts as a ligand for formyl peptide receptor-like 1 (FPRL1) and 2 (FPRL2). It has been demonstrated that HN plays a protective role through its antiapoptotic activity that interferes with Bax activation, which suppresses Bax-dependent apoptosis. HN has also been shown to suppress the c-Jun N-terminal kinase (JNK) and ASK/JNK-mediated neuronal cell death. Several studies have also confirmed that HN could be important in the prevention of angiopathy-associated Alzheimer's disease dementia, diseases related to mitochondrial dysfunction (MELAS), and other types of β-amyloid accumulation-associated neurodegeneration. Avery recent study demonstrated a pluripotent cytoprotective effect and mechanisms of HNs in cells not from the CNS, such as germ cells or pancreatic β-cells, and the potent physiological consequences that result from HN interaction with IGFBP3 and STAT3. In vivo studies suggest that HN may also protect against cognitive impairment due to ischemia/reperfusion injury.
Pharmacological reports: PR 62(5):767-77. · 2.44 Impact Factor
