Association of MMP1 and MMP3 haplotypes with myocardial infarction and echocardiographic parameters of the left ventricle

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

Variants Tagging LGALS-3 Haplotype Block in Association with First Myocardial Infarction and Plasma Galectin-3 Six Months after the Acute Event

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

Katja Pavlič Škerjanc septuagenaria

Ad multos anno

Pojmovanje revolucije v partizanskih dnevnikih Edvarda Kocbeka

Diplomsko delo poskuša osvetliti vprašanje, kako je v svojih dnevnikih, ki jih je med drugo svetovno vojno pisal v partizanih, revolucijo pojmoval pesnik, pisatelj in publicist, predstavnik krščansko-socialistične skupine v Izvršnem odboru Osvobodilne fronte slovenskega naroda Edvard Kocbek (1904-1981). V tem kontekstu je posebna pozornost namenjena vprašanju, ali so stališča o revoluciji, kakor jih najdemo zapisana v Kocbekovih knjižno izdanih partizanskih dnevnikih, vnazajšnja projekcija pisca, ki se je v povojnem obdobju znašel v opoziciji do oblasti Komunistične partije Slovenije, ali razmeroma zvest zapis njegovih stališč med samo drugo svetovno vojno. Avtor sicer izhaja iz predpostavke, da je Kocbek svoje pojmovanje radikalne družbene in osebne preobrazbe, ki ga v dnevnikih označuje z besedno zvezo "slovenska revolucija", zasnoval že v predvojnem obdobju, v času splošne evropske duhovne, politične in gospodarske krize, ko se je v slovenskem javnem življenju uveljavil kot eden vodilnih javnih intelektualcev na katoliški levici. Obenem avtor zagovarja stališče, da je Kocbekovo pojmovanje revolucije bistveno dopolnila izkušnja okupacije Slovenije in odločitev znatnega dela Slovenk in Slovencev za oborožen upor. Diplomsko delo sklepa prikaz ključnih elementov, ki določajo horizont pomenjanja slovenske revolucije. Po avtorjevem mnenju so to: vzajemno dopolnjevanje marksistične teorije in prakse ter krščanske ljubezniangažirani posameznik kot edini legitimni nosilec revolucijskega procesaekstatično osvobajanje posameznika od družbenih avtoritet ter slepega avtomatizma vsakdanjega malomeščanskega življenjazavest o nemožnosti katerekoli revolucije, da bi končnoveljavno razrešila vsa protislovja človeka kot duhovnega in socialnega bitja.Undergraduate thesis attempts to illuminate the question of the conception of revolution as outlined in the personal war-time journals of Edvard Kocbek (1904-1981), a renowned poet, writer, publicist and the representative of Christian socialists in the Executive Committee of the Liberation Front of the Slovene Nation. In this context special examination is given to the question of whether or not Kocbek\u27s views on revolution, as we can discern them from the published books, were substantially modified after the conclusion of the war, when Kocbek found himself in opposition to communist authorities. The author has based his examination of Kocbek\u27s "Slovene revolution", a process of radical personal and social metamorphosis, on the assumption that many aspects of this idea were already conceptualized by Kocbek in the interwar period of great pan-European spiritual, political and economic crisis, when Kocbek himself became widely regarded as one of the leading public intellectuals on the Slovene catholic left. The author further argues that Kocbek\u27s conceptualization of revolution was substantially emended by the experience of occupation and the subsequent decision of many Slovenes to take up arms against the occupying forces. The undergraduate thesis is concluded by a review of the key elements that define the horizon of meaning of Kocbek\u27s Slovene revolution. In author\u27s opinion these are: mutual intertwining of Marxist theory and practice and the concept of Christian lovean actively engaged individual as the only legitimate carrier of the revolutionary processan ecstatic liberation of the individual from the numbing powers of socio-political authority and blind automatism of everyday petit-bourgeois existencea clear understanding that no single one revolution can everlastingly resolve all the problems of the human being as a spiritual and social creature

Association of PHACTR1 intronic variants with the first myocardial infarction and their effect on PHACTR1 mRNA expression in PBMCs

Background: Myocardial infarction (MI) and underlining atherosclerosis are the main causes of death worldwide. Phosphatase and actin regulator 1 (PHACTR1) variants have been associated with early onset MI, coronary artery disease and carotid dissection. PHACTR1 mRNA expression has been detected in tissues and cells related to atherosclerosis. Nonetheless, the true effect of PHACTR1 on vascular diseases is still unknown. Our aim was to examine the association of PHACTR1 intronic variants, rs9349379, rs2026458 and rs2876300, with MI and multi-vessel disease (MVD) and to assess their effect on PHACTR1 and EDN1 mRNA expression in PBMCs of patients six months after MI. Methods: The study enrolled 537 patients with the first MI and 310 controls. Gene expression was assessed in 74 patients six months after MI and 37 healthy controls. Rs9349379, rs2026458, rs2876300 and relative mRNA expressions were detected by TaqMan® technology. Results: The significant association between PHACTR1 variants and MI was not found, either individually or in haplotype. A higher frequency of rs2876300G-allele in MVD was rendered not significant after Bonferroni correction. PHACTR1 mRNA was significantly increased in PBMCs of patients six months after MI compared to controls (p = 0.02). Patients that carry ACG haplotype have increased PHACTR1 mRNA expression in PBMCs (p = 0.04). There was no effect of PHACTR1 variants on EDN1 mRNA expression. Conclusion: Our findings suggest that PHACTR1 intronic variants may have a role in severity and progression of coronary atherosclerosis. Future research is needed to clarify the mechanism underlying the role of PHACTR1 in coronary atherosclerosis and MI. © 2021 Elsevier B.V

The association of glutathione S-transferase T1 and M1 deletions with myocardial infarction

Glutathione S-transferases (GSTs) are the family of enzymes involved in the second line of defense against oxidative stress (OS). The lack of GSTT1/GSTM1 enzyme quantity or activity, due to the presence of homozygous deletion compromises antioxidative defense resulting in OS. OS is the critical mechanism in the pathophysiology of atherosclerosis, coronary artery disease, and myocardial infarction (MI). The increase in reactive oxygen species together with the process of apoptosis plays a role in left ventricular remodeling (LVR) after MI. The associations of GSTT1 and GSTM1 gene polymorphisms with the risk of MI are inconsistent. The aim was to analyze the association of GSTT1/GSTM1 null genotypes with first MI and LVR 8 months after the MI. The study involved 330 controls and 438 consecutive patients with symptoms and signs of first MI. The subgroup of 150 MI patients was prospectively followed up for 6 months. Evidence of maladaptive LVR was obtained by 2D Doppler echocardiography 3-5 days and 6 months after the MI. A multiplex polymerase chain reaction was used to detect the deletion in GSTT1 and GSTM1 genes. GSTM1 null genotype was significantly and independently associated with first MI (adjusted OR = 1.45 95% CI 1.03-2.03, p = 0.03). Association of double null genotypes with maladaptive LVR in patients 6 months after the first MI was no longer significant after adjustment for factors that differed significantly between patients with and without maladaptive LVR. This study demonstrated the association of GSTM1 null genotypes with the risk of MI in the Serbian population

CDKN2B gene expression is affected by 9p21.3 rs10757278 in CAD patients, six months after the MI

Background: Chromosomal region 9p21.3 is most robustly associated with coronary artery disease (CAD) in western European populations. However, heterogeneity in CAD phenotypes leads to uncertainty whether 9p21.3 is associated with stable and/or acute clinical presentations of CAD. 9p21.3 is rich in regulatory elements, but the underlying mechanisms of its actions in CAD remain unclear. We investigate the association of 9p21.3 two haplotype blocks lead variants (rs10757278 and rs518394) with first-ever non-fatal myocardial infarction (MI) in CAD patients and their association with CDKN2B mRNA expression in peripheral blood mononuclear cells 6 months after the event. Methods: We included CAD patients with sustained first MI (n = 523) and controls (n = 583). Gene expression was assessed in 72 patients 6 months after MI and 43 healthy controls. TaqMan® technology was used for the gene expression and genotyping analysis. Results: CDKN2B mRNA was significantly lower in MI patients compared with the controls (p = 0.002) and in patients carrying the rs10757278 G risk allele versus AA homozygotes (p = 0.012) 6 months after the event. While we confirmed the association of rs10757278 with CDKN2B expression in MI patients, we failed to find an association between the investigated variants and MI or disease burden. Conclusions: We suggest a dysregulation of gene expression in the 9p21.3 region six months after acute MI, which is affected by a genetic variant in patients. The rs10757278 rare allele is one factor that might lead to prolonged risk for proatherogenic complications. © 2019 The Canadian Society of Clinical Chemist

HACD4 haplotype confers risk of myocardial infarction among males in the population of Serbia

86th Congress of the European-Atherosclerosis-Society (EAS), Lisbon,PORTUGAL, MAY 05-08, 201

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline