Faculty of Medicine

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Author: search.filters.author.Josifovska, SlavicaHas files: No

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    THE ROLE OF MATRIX METALLOPROTEINASE-1 AND ENDOTHELIAL NITRIC OXIDE SYNTHASE GENE POLYMORPHISMS IN DEVELOPMENT OF CORONARY ARTERY DISEASE
    (Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, 2024-07)
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    Josifovska, Slavica
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    Pakovski, Kiril
    Coronary artery disease (CAD) is one of the major causes of morbidity and mortality worldwide. The main pathophysiological processes involved in the development of CAD include impaired lipid metabolism, coagulation and chronic inflammation of the coronary vessel wall. There are many well-known traditional or conventional risk factors that may contribute to development of CAD like smoking cigarettes, lack of physical activity, diabetes, obesity, arterial hypertension, dyslipidemia (hypercholesterolemia), psychosocial stress etc. Nevertheless, over the last two decades there has been a significant progress in the field of genetic research and enlightening of the genetic basis of development of CAD. Certain genetic polymorphisms have been found to be linked not only to lipid metabolism and coagulation but also to inflammation and response, tissue maintenance, remodeling and degradation of the extracellular matrix. In this review article we discuss some of the most frequently studied gene polymorphisms in the development of CAD – matrix metalloproteinase-1 (MMP-1) and endothelial nitric oxide synthase (eNOS) gene polymorphisms.
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    ADRENAL GLAND TLR EXPRESSION IN ApoE DEFICIENT HOMOZYGOUS (ApoE KO-/-) MICE WITH IMPAIRED THYROID FUNCTION
    (Macedonian Association of Anatomists and Morphologists, 2023-12)
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    Josifovska, Slavica
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    The main aim of our study was to investigate the expression of TLR receptors in the adrenal gland of ApoE knockout mice in context of ApoE deficiency as well as impaired thyroid function (hypo- and hyperthyroidism). The study was conducted on two following experimental animal groups: hypothyroid homozygous mice (ApoE KO-/-) treated with PTU; hyperthyroid homozygous mice (ApoE KO-/-) treated with L-thyroxine (T4) and two control groups: euthyroid homozygous mice (ApoE KO-/-) and euthyroid wild-type C57BL/6 mice (Bb). Determination of TLR gene expression in the adrenal gland was performed by RT-PCR reaction with semi-quantitative detection of populations of mRNA molecules transcribed from the TLR2, TLR4 and TLR9 genes in the adrenal gland in the treated experimental groups and the two untreated control groups. The results of our study are in support of the hypothesis that both conditions of impaired thyroid function produce TLR agonists that increase the expression of TLR in the adrenal gland (p<0,05). Also, in the untreated/control group of mice (ApoE KO-/-), an increased expression of TLR was found compared to the wild strain C57BL/6 mice (Bb) as a control group (p<0.001).
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    Association of the APOEgene polymorphism with diabetic nephropathy
    (Bioscientifica, 2020-08)
    Hasan, Taner
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    Josifovska, Slavica
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    Trajkovska, Ivana
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    Doneva, Daniela
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    Nedeska, Natasha
    The protein isoformes that are products of the Apolipoprotein E (APOB) gene polymorphism have partially altered biological activity and that may lead to greater susceptibility of the patientsto microvascular complications including Diabetic nephropathy (DN)in patients with the Type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the association between the allele ε2, ε3, and ε4 of the APOE gene, as well as their combination, with the development of DN in patients with T2DM from the North Macedonia. The genotypic and allele frequency of the polymorphisms rs429358 and rs7412 in the APOE gene was determined in a group of patients with T2DM (with and without DN), and in the control group healthy subjects. The study is designed as a case-control genetic association study. The samples from 88 patients with T2DM were analyzed, including 57 patients with DN and 31 without DN and 26 healthy controls. The demographic, clinical and laboratory data were analyzed in addition to the genetic profiling of the patients. Genotyping of the APOE gene polymorphism resulted in determination of the patient’s genotype: ε2/ε2, ε3/ε3, ε4/ε4, ε2/ε3, ε2/ε4 or ε3/ε4, as well as of the alleles: ε2, ε3 or ε4. The results revealed a statistically significant association of the genotype ε2/ε3 (P = 0.016) and the allele ε2 (P = 0.020) with the occurrence of DN compared to the other genotypes and alleles. The presence of this genotype increases the chances of DN by 4,24 folds and the relative risk by 1,50 folds. In conclusion, the correlation of the APOEgene polymorphism and the development of the DN in patients with T2DM was confirmed indicating that there is a potential applicable value in the prognosis and treatment selection.