Browsing by Author "Djuric, Tamara (9734588600)"

Background: Myocardial infarction (MI) leads to ischemia and afterward to left ventricular (LV) remodeling. Matrix metalloproteinase−1 (MMP1) and −3 (MMP3) belong to the family of endopeptidases and together they can dissolve most of the components of the extracellular matrix. MMP1 and MMP3 variants have been investigated solely in association with ischemic heart disease and LV dysfunction, but not in haplotype. The aims of this study were to investigate the association of haplotypes inferred from MMP1 rs1799750 (−1607 1G/2G; NC_000011.9:g.102670497del) and MMP3 rs35068180 (−1612 5A/6A; NC_000011.9:g.102715952dup) with MI and their effect on the change in echocardiographic parameters of LV structure and function in patients within 6 months after MI. Methods: The study included 325 patients with the first MI and 283 healthy controls. Gene variants were detected by PCR-RFLP method. Parameters of LV structure and function were assessed by conventional 2D echocardiography, 3–5 days and 6 months after the first MI, on a subgroup of 160 patients. Haplotype analysis was performed with Thesias software. Results: Haplotypes 2G-5A and 1G-6A were significantly and independently associated with MI compared with the reference haplotype 2G-6A (adjusted, p = 0.009 and p = 0.026, respectively). After Bonferroni correction for multiple testing, MMP1 and MMP3 haplotypes lost their association with the change in LV long diameter and stroke volume within 6 months after MI. Conclusion: MMP1 and MMP3 haplotypes are strongly associated with MI. Further studies are needed to validate this result and to examine their association with echocardiographic parameters of LV structure and function after MI. © 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.

Background: Myocardial infarction (MI) leads to ischemia and afterward to left ventricular (LV) remodeling. Matrix metalloproteinase−1 (MMP1) and −3 (MMP3) belong to the family of endopeptidases and together they can dissolve most of the components of the extracellular matrix. MMP1 and MMP3 variants have been investigated solely in association with ischemic heart disease and LV dysfunction, but not in haplotype. The aims of this study were to investigate the association of haplotypes inferred from MMP1 rs1799750 (−1607 1G/2G; NC_000011.9:g.102670497del) and MMP3 rs35068180 (−1612 5A/6A; NC_000011.9:g.102715952dup) with MI and their effect on the change in echocardiographic parameters of LV structure and function in patients within 6 months after MI. Methods: The study included 325 patients with the first MI and 283 healthy controls. Gene variants were detected by PCR-RFLP method. Parameters of LV structure and function were assessed by conventional 2D echocardiography, 3–5 days and 6 months after the first MI, on a subgroup of 160 patients. Haplotype analysis was performed with Thesias software. Results: Haplotypes 2G-5A and 1G-6A were significantly and independently associated with MI compared with the reference haplotype 2G-6A (adjusted, p = 0.009 and p = 0.026, respectively). After Bonferroni correction for multiple testing, MMP1 and MMP3 haplotypes lost their association with the change in LV long diameter and stroke volume within 6 months after MI. Conclusion: MMP1 and MMP3 haplotypes are strongly associated with MI. Further studies are needed to validate this result and to examine their association with echocardiographic parameters of LV structure and function after MI. © 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.

Background: After myocardial infarction (MI), adverse left ventricular (LV) remodeling may occur. This is followed by LV hypertrophy and eventually heart failure. The remodeling process is complex and goes through multiple phases. The aim of this study was to investigate the expression of HMGB1, TGF-β1, BIRC3, ADAM17, CDKN1A, and FTO, each involved in a specific step of LV remodeling, in association with the change in the echocardiographic parameters of LV structure and function used to assess the LV remodeling process in the peripheral blood mononuclear cells (PBMCs) of patients six months after the first MI. The expression of selected genes was also determined in PBMCs of controls. Methods: The study group consisted of 99 MI patients, who were prospectively followed-up for 6 months, and 25 controls. Cardiac parameters, measured via conventional 2D echocardiography, were evaluated at two time points: 3–5 days and 6 months after MI. The mRNA expression six-months-post-MI was detected using TaqMan® technology (Applied Biosystems, Thermo Fisher Scientific, Waltham, MA, USA). Results: HMGB1 mRNA was significantly higher in patients with adverse LV remodeling six-months-post-MI than in patients without adverse LV remodeling (p = 0.04). HMGB1 mRNA was significantly upregulated in patients with dilated LV end-diastolic diameter (LVEDD) (p = 0.03); dilated LV end-diastolic volume index (LVEDVi) (p = 0.03); severely dilated LV end-systolic volume index (LVESVi) (p = 0.006); impaired LV ejection fraction (LVEF) (p = 0.01); and LV enlargement (p = 0.03). It was also significantly upregulated in PBMCs from patients compared to controls (p = 0.005). TGF-β1 and BIRC3 mRNA were significantly lower in patients compared to controls (p = 0.02 and p = 0.05, respectively). Conclusions: Our results suggest that HMGB1 is involved in adverse LV remodeling six-months-post-MI, even on the mRNA level. Further research and validation are needed. © 2024 by the authors.

Background: After myocardial infarction (MI), adverse left ventricular (LV) remodeling may occur. This is followed by LV hypertrophy and eventually heart failure. The remodeling process is complex and goes through multiple phases. The aim of this study was to investigate the expression of HMGB1, TGF-β1, BIRC3, ADAM17, CDKN1A, and FTO, each involved in a specific step of LV remodeling, in association with the change in the echocardiographic parameters of LV structure and function used to assess the LV remodeling process in the peripheral blood mononuclear cells (PBMCs) of patients six months after the first MI. The expression of selected genes was also determined in PBMCs of controls. Methods: The study group consisted of 99 MI patients, who were prospectively followed-up for 6 months, and 25 controls. Cardiac parameters, measured via conventional 2D echocardiography, were evaluated at two time points: 3–5 days and 6 months after MI. The mRNA expression six-months-post-MI was detected using TaqMan® technology (Applied Biosystems, Thermo Fisher Scientific, Waltham, MA, USA). Results: HMGB1 mRNA was significantly higher in patients with adverse LV remodeling six-months-post-MI than in patients without adverse LV remodeling (p = 0.04). HMGB1 mRNA was significantly upregulated in patients with dilated LV end-diastolic diameter (LVEDD) (p = 0.03); dilated LV end-diastolic volume index (LVEDVi) (p = 0.03); severely dilated LV end-systolic volume index (LVESVi) (p = 0.006); impaired LV ejection fraction (LVEF) (p = 0.01); and LV enlargement (p = 0.03). It was also significantly upregulated in PBMCs from patients compared to controls (p = 0.005). TGF-β1 and BIRC3 mRNA were significantly lower in patients compared to controls (p = 0.02 and p = 0.05, respectively). Conclusions: Our results suggest that HMGB1 is involved in adverse LV remodeling six-months-post-MI, even on the mRNA level. Further research and validation are needed. © 2024 by the authors.

Background: Previous research has shown that there is an association between galectin-3 (gal-3) protein and cardiovascular pathology. The aim of this study was to investigate the effects of rs2274273 and rs17128183 on genetic susceptibility to advanced carotid atherosclerosis (CA) and its complications. The rs2274273 has been singled out as the lead SNP of the haplotype block containing LGALS-3 (gal-3 gene) associated with gal-3 circulating levels, while rs17128183 constitutes a potentially functional SNP of the same hap-block. We further sought to determine whether these genetic variants have an impact on the expression of LGALS-3 mRNA in human carotid atherosclerotic plaque tissue. Methods: The study encompassed 300 control subjects and 485 patients with advanced CA who had undergone carotid endarterectomy. Rs2274273, rs17128183, and LGALS-3 relative mRNA expression was detected by means of real-time PCR (TaqMan® technology). Results: There were no statistically significant associations of the investigated genetic variants with susceptibility to advanced CA, nor did we find any associations in terms of ultrasonographically defined plaque phenotypes. The relative expression of LGALS-3 mRNA proved to be significantly higher in carriers of the rare alleles (P = 0.039) for both genetic variants. Conclusion: Our exploratory results suggest that while rs2274273 and rs17128183 bear no association with the risk of advanced CA or CA-related complications, these genetic variants are likely to affect LGALS-3 expression levels. In order to reach a definitive conclusion on the role played by rs2274273 and rs17128183 in advanced CA, our results should be further validated. © 2016 Wiley Periodicals, Inc.

Background: Previous research has shown that there is an association between galectin-3 (gal-3) protein and cardiovascular pathology. The aim of this study was to investigate the effects of rs2274273 and rs17128183 on genetic susceptibility to advanced carotid atherosclerosis (CA) and its complications. The rs2274273 has been singled out as the lead SNP of the haplotype block containing LGALS-3 (gal-3 gene) associated with gal-3 circulating levels, while rs17128183 constitutes a potentially functional SNP of the same hap-block. We further sought to determine whether these genetic variants have an impact on the expression of LGALS-3 mRNA in human carotid atherosclerotic plaque tissue. Methods: The study encompassed 300 control subjects and 485 patients with advanced CA who had undergone carotid endarterectomy. Rs2274273, rs17128183, and LGALS-3 relative mRNA expression was detected by means of real-time PCR (TaqMan® technology). Results: There were no statistically significant associations of the investigated genetic variants with susceptibility to advanced CA, nor did we find any associations in terms of ultrasonographically defined plaque phenotypes. The relative expression of LGALS-3 mRNA proved to be significantly higher in carriers of the rare alleles (P = 0.039) for both genetic variants. Conclusion: Our exploratory results suggest that while rs2274273 and rs17128183 bear no association with the risk of advanced CA or CA-related complications, these genetic variants are likely to affect LGALS-3 expression levels. In order to reach a definitive conclusion on the role played by rs2274273 and rs17128183 in advanced CA, our results should be further validated. © 2016 Wiley Periodicals, Inc.

Objectives/Hypothesis: To establish comprehensive transcriptomic profiles of cholesteatoma perimatrix tissue and granulation tissue from chronic otitis media (COM) that did not develop cholesteatoma, which can indicate molecular pathways involved in the cholesteatoma perimatrix pathology and invasiveness. Study Design: Retrospective Case Series. Methods: Transcriptome data were obtained from cholesteatoma perimatrix tissue and COM granulation tissue by an Illumina iScan microarray. Differentially expressed genes (DEGs) were subsequently analyzed using both bioinformatical functional annotation and network analysis. Expression of candidate genes (MMP9 and LCN2) was validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on a larger group of samples. Results: Analysis of the transcriptome led to the identification of 169 differentially expressed genes between investigated tissues. Bioinformatic analysis suggested that most significant biological processes involving DEGs were previously described in cholesteatoma pathology. Network analysis identified ERBB2, TFAP2A, and TP63 as major hubs of the DEGs molecular network. Furthermore, it was observed that the cellular component most significantly enriched in DEGs was extracellular space containing 47 DEGs. Using qRT-PCR, it was confirmed that mRNA levels of the major extracellular hub (MMP9) are increased, whereas its interacting molecule (LCN2) mRNA levels were decreased in cholesteatoma perimatrix tissue compared to COM granulation tissue. Conclusions: The current study approach offers an overall look at molecular mechanisms that describe the cholesteatoma entity by focusing exclusively on the perimatrix processes in comparison to COM granulation tissue. The observed differences in gene expression between cholesteatoma perimatrix and COM granulation tissue could suggest novel markers potentially influenced by the perimatrix–matrix molecular interplay, which is not present in COM without cholesteatoma. Level of Evidence: NA. Laryngoscope, 130:E220–E227, 2020. © 2019 The American Laryngological, Rhinological and Otological Society, Inc.

Backgrounds: Galectin-3 (gal-3) is upregulated in remodeling, and failing myocardium and gal-3 levels are increased in hypertrophy, fibrosis and inflammation. The aim of this study was to investigate the potential role of sex-related differences in the following: risk factors, left ventricular (LV) structural and functional changes, coronary angiography, expression of the gal-3 encoding gene LGALS-3 and plasma gal-3 levels in heart failure (HF). Materials and Methods: This prospective study included 137 men and 44 women with first MI who underwent Doppler echocardiography within 2–4 days of MI and after 6 months. Relative LGALS-3 mRNA expression in peripheral blood mononuclear cells (PBMCs) was detected using TaqMan® technology. Plasma gal-3 concentration was determined by ELISA method. Results: In the acute phase of MI, LV end-diastolic and end-systolic volume indexes (LVEDVI and LVESVI) were significantly lower in women compared to men (58.2 ± 13.1 vs. 46.3 ± 11.1, p < 0.001; 33.7 ± 9.5 vs. 27.0 ± 9.2, p < 0.001, respectively). The incidence of LV hypertrophy (LVH) and HF was significantly higher in women compared to men (70.0% vs. 44.6%, p = 0.03; 37.5% vs.19.5%, p = 0.02, respectively). There was a significant correlation between the grade of LV diastolic dysfunction (LVDD) and plasma gal-3 levels (p < 0.001). The relative expression of LGALS-3 mRNA in PBMCs was higher in females (fold induction = 1.326, S.E. range = 0.748–2.587, p = 0.007). Plasma gal-3 levels were higher in women compared to men (44.66 ± 28.04 vs. 16.30 ± 12.68, p < 0.001) and higher in patients with HF than in patients without HF (31.14 ± 27.09 vs.21.39 ± 18.17, p = 0.025). Conclusions: Gender-specific factors such as LVH, LVDD, LGALS-3 mRNA expression and plasma gal-3 levels may explain the increased incidence of HF in women. The differences in the model and determinants of HF between men and women may be relevant for further therapeutic strategies including the inhibition of gal-3. © 2024 by the authors.

Backgrounds: Galectin-3 (gal-3) is upregulated in remodeling, and failing myocardium and gal-3 levels are increased in hypertrophy, fibrosis and inflammation. The aim of this study was to investigate the potential role of sex-related differences in the following: risk factors, left ventricular (LV) structural and functional changes, coronary angiography, expression of the gal-3 encoding gene LGALS-3 and plasma gal-3 levels in heart failure (HF). Materials and Methods: This prospective study included 137 men and 44 women with first MI who underwent Doppler echocardiography within 2–4 days of MI and after 6 months. Relative LGALS-3 mRNA expression in peripheral blood mononuclear cells (PBMCs) was detected using TaqMan® technology. Plasma gal-3 concentration was determined by ELISA method. Results: In the acute phase of MI, LV end-diastolic and end-systolic volume indexes (LVEDVI and LVESVI) were significantly lower in women compared to men (58.2 ± 13.1 vs. 46.3 ± 11.1, p < 0.001; 33.7 ± 9.5 vs. 27.0 ± 9.2, p < 0.001, respectively). The incidence of LV hypertrophy (LVH) and HF was significantly higher in women compared to men (70.0% vs. 44.6%, p = 0.03; 37.5% vs.19.5%, p = 0.02, respectively). There was a significant correlation between the grade of LV diastolic dysfunction (LVDD) and plasma gal-3 levels (p < 0.001). The relative expression of LGALS-3 mRNA in PBMCs was higher in females (fold induction = 1.326, S.E. range = 0.748–2.587, p = 0.007). Plasma gal-3 levels were higher in women compared to men (44.66 ± 28.04 vs. 16.30 ± 12.68, p < 0.001) and higher in patients with HF than in patients without HF (31.14 ± 27.09 vs.21.39 ± 18.17, p = 0.025). Conclusions: Gender-specific factors such as LVH, LVDD, LGALS-3 mRNA expression and plasma gal-3 levels may explain the increased incidence of HF in women. The differences in the model and determinants of HF between men and women may be relevant for further therapeutic strategies including the inhibition of gal-3. © 2024 by the authors.

Objectives: Galectin-3 affects a variety of biological processes. It is encoded by LGALS-3, located in unique haplotype block in Caucasians. Most of the studies regarding the gal-3 role in atherosclerosis are focused exclusively on protein/mRNA levels. Genetic analyses of LGALS-3 are scarce. We sought to thoroughly examine the genetic background of gal-3 and to analyze tag variants that cover more than 80% variability of the LGALS-3 containing hap-block in association with carotid plaque presence (CPP). According to Tagger server, rs4040064 G/T, rs11628437 G/A and rs7159490 C/T cover 82% (r2 > 0.8) of the genetic variance of this hap-block. Our aims were to investigate possible association of rs4040064, rs11628437 and rs7159490 haplotypes with CPP in patients with advanced carotid atherosclerosis (CA) and to analyze their possible effect on LGALS-3 mRNA expression in carotid plaques. Materials and methods: Study group consisted of 468 patients and 296 controls. Rs4040064, rs11628437, rs7159490 and LGALS-3 mRNA expression were detected by TaqMan® technology. Results: We have found that haplotype TAC was associated with the cerebrovascular insult (CVI) occurrence (OR = 1.68, 95% CI = 1.09-2.58, p = 0.02), compared to the referent haplotype. OR was adjusted for hypertension, age and BMI. TAC also showed higher, but not statistically significant, LGALS-3 expression in carotid plaques. Conclusions: Our results suggest that rs4040064, rs11628437 and rs7159490 bear no association with CPP, neither they affect LGALS-3 mRNA in carotid plaques. However, we showed a significant association of haplotype TAC with the CVI occurrence in CA patients from Serbia. Replication and validation of our results are required. © 2021 Elsevier Inc.

Galectin-3 is encoded by LGALS-3, located in a unique haplotype block in Caucasians. According to the Tagger server, rs4040064, rs11628437, and rs7159490 cover 82% (r2 > 0.8) of the genetic variance of this HapBlock. Our aims were to examine the association of their haplotypes with first myocardial infarction (MI), changes in left ventricular echocardiographic parameters over time, and impact on plasma galectin-3 and LGALS-3 mRNA in peripheral blood mononuclear cells, both 6 months post-MI. The study group consisted of 546 MI patients and 323 controls. Gene expression was assessed in 92 patients and plasma galectin-3 in 189 patients. Rs4040064, rs11628437, rs7159490, and LGALS-3 mRNA expression were detected using TaqMan® technology. Plasma galectin-3 concentrations were determined by the ELISA method. We found that the TGC haplotype could have a protective effect against MI (adjusted OR 0.19 [0.05–0.72], p = 0.015) and that the GAC haplotype had significantly higher galectin-3 concentrations (48.3 [37.3–59.4] ng/mL vs. 18.9 [14.5–23.4] ng/mL, p < 0.0001), both in males and compared to the referent haplotype GGC. Higher plasma Gal-3 was also associated with higher NYHA class and systolic dysfunction. Our results suggest that variants tagging LGALS-3 HapBlock could reflect plasma Gal-3 levels 6 months post-MI and may have a potential protective effect against MI in men. Further replication, validation, and functional studies are needed. © 2022 by the authors.

Galectin-3 is encoded by LGALS-3, located in a unique haplotype block in Caucasians. According to the Tagger server, rs4040064, rs11628437, and rs7159490 cover 82% (r2 > 0.8) of the genetic variance of this HapBlock. Our aims were to examine the association of their haplotypes with first myocardial infarction (MI), changes in left ventricular echocardiographic parameters over time, and impact on plasma galectin-3 and LGALS-3 mRNA in peripheral blood mononuclear cells, both 6 months post-MI. The study group consisted of 546 MI patients and 323 controls. Gene expression was assessed in 92 patients and plasma galectin-3 in 189 patients. Rs4040064, rs11628437, rs7159490, and LGALS-3 mRNA expression were detected using TaqMan® technology. Plasma galectin-3 concentrations were determined by the ELISA method. We found that the TGC haplotype could have a protective effect against MI (adjusted OR 0.19 [0.05–0.72], p = 0.015) and that the GAC haplotype had significantly higher galectin-3 concentrations (48.3 [37.3–59.4] ng/mL vs. 18.9 [14.5–23.4] ng/mL, p < 0.0001), both in males and compared to the referent haplotype GGC. Higher plasma Gal-3 was also associated with higher NYHA class and systolic dysfunction. Our results suggest that variants tagging LGALS-3 HapBlock could reflect plasma Gal-3 levels 6 months post-MI and may have a potential protective effect against MI in men. Further replication, validation, and functional studies are needed. © 2022 by the authors.