Browsing by Author "Kuveljic, Jovana (56667762900)"

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.

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.