Assessment of Myocardial Diastolic Dysfunction as a Result of Myocardial Infarction and Extracellular Matrix Regulation Disorders in the Context of Mesenchymal Stem Cell Therapy.

The decline in cardiac contractility due to damage or loss of cardiomyocytes is intensified by changes in the extracellular matrix leading to heart remodeling. An excessive matrix response in the ischemic cardiomyopathy may contribute to the elevated fibrotic compartment and diastolic dysfunction. Fibroproliferation is a defense response aimed at quickly closing the damaged area and maintaining tissue integrity. Balance in this process is of paramount importance, as the reduced post-infarction response causes scar thinning and more pronounced left ventricular remodeling, while excessive fibrosis leads to impairment of heart function. Under normal conditions, migration of progenitor cells to the lesion site occurs. These cells have the potential to differentiate into myocytes in vitro, but the changed micro-environment in the heart after infarction does not allow such differentiation. Stem cell transplantation affects the extracellular matrix remodeling and thus may facilitate the improvement of left ventricular function. Studies show that mesenchymal stem cell therapy after infarct reduces fibrosis. However, the authors did not specify whether they meant the reduction of scarring as a result of regeneration or changes in the matrix. Research is also necessary to rule out long-term negative effects of post-acute infarct stem cell therapy.

Analysis of Genetic Variants in the Glucocorticoid Receptor Gene NR3C1 and Stenosis of the Carotid Artery in a Polish Population with Coronary Artery Disease.

Background: Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Early diagnosis and elimination of risk factors are crucial for better managing CVDs. Atherosclerosis, whose development might be associated with glucocorticoids (GCs), is a critical factor in the development of carotid artery (CA) stenosis and most other CVDs. Aim: To investigate the association of Tth111I, N363S, and ER22/23EK-NR3C1 polymorphisms and the incidence of CA stenosis. Methods: The study group consisted of 117 patients diagnosed with coronary artery disease (CAD) and CA stenosis and 88 patients with CAD and ruled out CA stenosis. Genomic DNA was extracted from blood, and genotyping was carried out using Tth111I, N363S, and ER22/23EK-NR3C1 polymorphism sequencing. Results: No significant association between studied polymorphisms and the incidence or the severity of CA stenosis in the Polish population with CAD was found. Conclusion: This is the first study that proves that common NR3C1 gene variants do not influence CA stenosis and probably are not associated with atherosclerosis. The search for genes that can act as prognostic markers in predicting CA stenosis is still ongoing.

Human Cell Organelles in SARS-CoV-2 Infection: An Up-to-Date Overview.

Since the end of 2019, the whole world has been struggling with the life-threatening pandemic amongst all age groups and geographic areas caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). The Coronavirus Disease 2019 (COVID-19) pandemic, which has led to more than 468 million cases and over 6 million deaths reported worldwide (as of 20 March 2022), is one of the greatest threats to human health in history. Meanwhile, the lack of specific and irresistible treatment modalities provoked concentrated efforts in scientists around the world. Various mechanisms of cell entry and cellular dysfunction were initially proclaimed. Especially, mitochondria and cell membrane are crucial for the course of infection. The SARS-CoV-2 invasion depends on angiotensin converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), and cluster of differentiation 147 (CD147), expressed on host cells. Moreover, in this narrative review, we aim to discuss other cell organelles targeted by SARS-CoV-2. Lastly, we briefly summarize the studies on various drugs.

Efficacy of AutoPulse for Mechanical Chest Compression in Patients with Shock-Resistant Ventricular Fibrillation.

INTRODUCTION: Sudden cardiac arrest is one of the most common causes of death. In cases of shock-resistant ventricular fibrillation, immediate transport of patients to the hospital is essential and made possible with use of devices for mechanical chest compression. OBJECTIVES: The efficacy of AutoPulse in patients with shock-resistant ventricular fibrillation was studied. METHODS: This is a multicentre observational study on a population of 480,000, with 192 reported cases of out-of-hospital cardiac arrest. The study included patients with shock-resistant ventricular fibrillation defined as cardiac arrest secondary to ventricular fibrillation requiring ≥3 consecutive shocks. Eventually, 18 patients met the study criteria. RESULTS: The mean duration of resuscitation was 48.4±43 min, 55% of patients were handed over to the laboratory while still in cardiac arrest, 83.3% of them underwent angiography and, in 93.3% of them, infarction was confirmed. Coronary intervention was continued during mechanical resuscitation in 50.0% of patients, 60% of patients survived the procedure, and 27.8% of the patients survived. CONCLUSIONS: Resistant ventricular fibrillation suggests high likelihood of a coronary component to the cardiac arrest. AutoPulse is helpful in conducting resuscitation, allowing the time to arrival at hospital to be reduced.

CXCR2 Receptor: Regulation of Expression, Signal Transduction, and Involvement in Cancer.

Chemokines are a group of about 50 chemotactic cytokines crucial for the migration of immune system cells and tumor cells, as well as for metastasis. One of the 20 chemokine receptors identified to date is CXCR2, a G-protein-coupled receptor (GPCR) whose most known ligands are CXCL8 (IL-8) and CXCL1 (GRO-α). In this article we present a comprehensive review of literature concerning the role of CXCR2 in cancer. We start with regulation of its expression at the transcriptional level and how this regulation involves microRNAs. We show the mechanism of CXCR2 signal transduction, in particular the action of heterotrimeric G proteins, phosphorylation, internalization, intracellular trafficking, sequestration, recycling, and degradation of CXCR2. We discuss in detail the mechanism of the effects of activated CXCR2 on the actin cytoskeleton. Finally, we describe the involvement of CXCR2 in cancer. We focused on the importance of CXCR2 in tumor processes such as proliferation, migration, and invasion of tumor cells as well as the effects of CXCR2 activation on angiogenesis, lymphangiogenesis, and cellular senescence. We also discuss the importance of CXCR2 in cell recruitment to the tumor niche including tumor-associated neutrophils (TAN), tumor-associated macrophages (TAM), myeloid-derived suppressor cells (MDSC), and regulatory T (Treg) cells.

Concentrations of Mg, Ca, Fe, Cu, Zn, P and anthropometric and biochemical parameters in adults with chronic heart failure.

BACKGROUND: The study investigated the relationship between the concentrations of Mg, Ca, Fe, Cu, Zn, P and anthropometric and biochemical parameters in the blood serum of patients with heart failure (HF) and the potential influence on the development and progression of HF. MATERIAL & METHODS: The study included 214 patients (155 men and 59 women), aged 40-87 years, presenting symptoms or signs typical of HF (according to the NYHA functional classification). Serum concentrations were determined for Mg, Ca, Fe, Cu, Zn, P, C-reactive protein (CRP), creatinine, urea, triglyceride levels (TG), total cholesterol (CH), high density protein (HDL), low density protein (LDL). The levels of macro-and microminerals were analysed using inductively coupled serum optical emission spectrometry (ICP-OES). RESULTS: Our study confirmed the role of known risk factors in the development of heart failure, including: overweight, diabetes, hypertension, high triglycerides (TG), high total cholesterol (CH), high levels of low density protein (LDL) and reduced levels of high density protein (HDL), high CRP, high creatinine. Moreover, deficient serum concentrations of Mg (47% of the studied men and 54% of the women) and Cu (in 44% of men and more than 30% of women) were observed, as well as subnormal serum Fe (2% of women) and Zn (1% of men). Elevated serum Ca was found in 50% of men and 49% of women. In 44% of the studied men and 52% of the studied women, P levels in serum were also above-average. The study revealed a significant positive correlation between serum levels of Ca and Mg, and also Ca and Cu in women. In men, serum Cu was positively correlated with Mg and Ca concentrations. In patients from group 1 (NYHA I-II), Mg content was positively correlated with Ca and Cu. In this patient group, Ca was also positively associated with Cu content in serum. In group 2 (NYHA III-IV), serum Mg concentration was significantly positively correlated with that of Cu and Ca. CONCLUSIONS: Changes in the serum concentrations of macro-and microminerals may significantly affect the severity of HF in Polish patients.

The importance of the UGT1A1 variants in the development of osteopenia and osteoporosis in postmenopausal women.

The UDP-glucuronosyltransferase 1A1 (UGT1A1) is involved in the process of estrogen conjugation and elimination. The aim of the study was to analyze whether the UGT1A1 genetic variants are associated with the development of osteopenia and osteoporosis in postmenopausal women. The analysis of the rs4148323 (UGT1A1*6) and rs3064744 (UGT1A1*28) variants in the UGT1A1 gene was conducted using real-time PCR. A significant correlation was observed between the genotypes of the rs3064744 (UGT1A1*28) sequence variant and body mass in women with osteoporosis. The analysis of the Z-score values revealed that women with osteoporosis and carrying the 6/6 variant had the lowest Z-score values as compared to women with the 6/7 and the 7/7 variants (- 1.966 ± 0.242 vs. - 1.577 ± 0.125 and - 1.839 ± 0.233). In addition, the odds ratio for the investigated genotypes (6/6, 6/7, 7/7) indicated an increased risk for osteopenia and osteoporosis in women with the 7/7 homozygous genotype. The analysis of the frequencies of the GG, GA and AA genotypes of the rs4148323 UGT1A1 gene showed no statistically significant differences between the groups. Our analysis revealed that the UGT1A1 rs3064744 variant may affect the risk of developing osteoporosis in postmenopausal Polish women. The UGT1A1 rs4148323 variant is not directly associated with the development of osteopenia and osteoporosis.

The Analysis of NADPH Quinone Reductase 1 (NQO1) Polymorphism in Polish Patients with Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common malignancies in Poland. Based on the findings of clinical trials, it is safe to conclude that genetic predisposition and environmental factors are the main factors responsible for the formation of colorectal cancer.The NQO1 gene plays an important role in reducing endogenous and exogenous quinones as well as quinone compounds to hydroquinones. It is an enzyme which is a part of the body's antioxidant defense system. The aim of the study was to evaluate the correlation between the 609C > T polymorphism of the NQO1 gene and colorectal cancer risk in the Polish population. A total of 512 people were recruited for the study, including 279 patients with colorectal cancer, diagnosed at the University Hospital, Pomeranian Medical University in Szczecin. Genomic DNA was isolated from peripheral blood and the analyzed polymorphism was determined by PCR-RFLP. In the present study, we analyzed the clinical valuesand frequency of NQO1 609C > T polymorphism in patients diagnosed with colorectal cancer and controls. In case of the carriers of the TT genotype of the NQO1 polymorphism, an elevated risk for colorectal cancer was observed (OR = 2.96; 95% CI: 1.02-10.40). The analysis of the clinical parameters concerning the location and characteristics of the tumor stage revealed a statistically significant increase in the risk for colorectal cancer in the carriers of the TT genotype of the NQO1 polymorphism.

A new approach to ticagrelor-based de-escalation of antiplatelet therapy after acute coronary syndrome. A rationale for a randomized, double-blind, placebo-controlled, investigator-initiated, multicenter clinical study.

The risk of ischemic events gradually decreases after acute coronary syndrome (ACS), reaching a stable level after 1 month, while the risk of bleeding remains steady during the whole period of dual antiplatelet treatment (DAPT). Several de-escalation strategies of antiplatelet treatment aiming to enhance safety of DAPT without depriving it of its efficacy have been evaluated so far. We hypothesized that reduction of the ticagrelor maintenance dose 1 month after ACS and its continuation until 12 months after ACS may improve adherence to antiplatelet treatment due to better tolerability compared with the standard dose of ticagrelor. Moreover, improved safety of treatment and preserved anti-ischemic benefit may also be expected with additional acetylsalicylic acid (ASA) withdrawal. To evaluate these hypotheses, we designed the Evaluating Safety and Efficacy of Two Ticagrelor-based De-escalation Antiplatelet Strategies in Acute Coronary Syndrome - a randomized clinical trial (ELECTRA-SIRIO 2), to assess the influence of ticagrelor dose reduction with or without continuation of ASA versus DAPT with standard dose ticagrelor in reducing clinically relevant bleeding and maintaining anti-ischemic efficacy in ACS patients. The study was designed as a phase III, randomized, multicenter, double-blind, investigator-initiated clinical study with a 12-month follow-up (ClinicalTrials.gov Identifier: NCT04718025; EudraCT number: 2020-005130-15).

Procedural and 1-year outcomes following large vessel coronary artery perforation treated by covered stents implantation: Multicentre CRACK registry.

BACKGROUND: Data regarding the clinical outcomes of covered stents (CSs) used to seal coronary artery perforations (CAPs) in the all-comer population are scarce. The aim of the CRACK Registry was to evaluate the procedural, 30-days and 1-year outcomes after CAP treated by CS implantation. METHODS: This multicenter all-comer registry included data of consecutive patients with CAP treated by CS implantation. The primary endpoint was the composite of major adverse cardiac events (MACEs), defined as cardiac death, target lesion revascularization (TLR), and myocardial infarction (MI). RESULTS: The registry included 119 patients (mean age: 68.9 ± 9.7 years, 55.5% men). Acute coronary syndrome, including: unstable angina 21 (17.6%), NSTEMI 26 (21.8%), and STEMI 26 (21.8%), was the presenting diagnosis in 61.3%, and chronic coronary syndromes in 38.7% of patients. The most common lesion type, according to ACC/AHA classification, was type C lesion in 47 (39.5%) of cases. A total of 52 patients (43.7%) had type 3 Ellis classification, 28 patients (23.5%) had type 2 followed by 39 patients (32.8%) with type 1 perforation. Complex PCI was performed in 73 (61.3%) of patients. Periprocedural death occurred in eight patients (6.7%), of which two patients had emergency cardiac surgery. Those patients were excluded from the one-year analysis. Successful sealing of the perforation was achieved in 99 (83.2%) patients. During the follow-up, 26 (26.2%) patients experienced MACE [7 (7.1%) cardiac deaths, 13 (13.1%) TLR, 11 (11.0%) MIs]. Stent thrombosis (ST) occurred in 6 (6.1%) patients [4(4.0%) acute ST, 1(1.0%) subacute ST and 1(1.0%) late ST]. CONCLUSIONS: The use of covered stents is an effective treatment of CAP. The procedural and 1-year outcomes of CAP treated by CS implantation showed that such patients should remain under follow-up due to relatively high risk of MACE.

The importance of NFκB1 rs4648068 and RUNX2 rs7771980 polymorphisms in bone metabolism of postmenopausal Polish women.

OBJECTIVES: Osteoporosis is a multifactorial disease that causes a loss of bone density. However, genetic factors play an increasingly important role in its development. To thoroughly understand the molecular mechanisms, polymorphic variants of genes candidate for osteoporosis are still being sought. The aim of our study was to investigate the influence of NFκB1 gene rs4648068 (A>G) and RUNX2 gene rs7771980 (-1025T>C) polymorphisms on the risk of osteoporosis. MATERIAL AND METHODS: A group of 675 postmenopausal Caucasian women (109 women with osteopenia, 333 with osteoporosis and 233 with normal T-score) were examined. The bone mineral density (BMD) at the lumbar spine (L1-L4) was measured by dual energy x-ray absorptiometry (DXA). The analysis of NFκB1 and RUNX2 polymorphisms was performed using real-time PCR method. RESULTS: Analysis of NFκB1 gene rs4648068 polymorphism showed that the GG genotype was slightly more frequent in the study groups compared to the control group. In the osteoporosis group, patients with the G allele in the genotype have lower bone mineral density values. For the RUNX2 rs7771980 polymorphism, in women with osteopenia we observed an increased incidence of TC heterozygotes compared to the control group (29.40% vs 24.90%, p > 0.05), and in women with osteoporosis, the TT genotype was more common (78.70% vs 73.80%, p > 0.05). No correlation was observed between the genotypes and the clinical parameters. CONCLUSIONS: The analysis showed no significant relationship between the genotypic distribution and the individual clinical parameters. However, it is suggested an association between the rs4648068 polymorphism of the NFκB1 gene and an increased risk of developing osteoporosis.

ANalgesic Efficacy and safety of MOrphiNe versus methoxyflurane in patients with acute myocardial infarction: the rationale and design of the ANEMON-SIRIO 3 study: a multicentre, open-label, phase II, randomised clinical trial.

INTRODUCTION: The unfavourable influence of morphine on the pharmacokinetics of ticagrelor resulting in weaker and retarded antiplatelet effect in patients with acute coronary syndrome (ACS) has been previously shown. Replacing morphine with methoxyflurane, a potent, non-opioid analgesic agent, that does not weaken or delay the effect of antiplatelet agents may improve the clinical efficacy of treatment of patients with ACS. METHODS: The ANEMON-SIRIO 3 study was designed as a multicentre, open-label, phase II, randomised clinical trial aimed to test the analgesic efficacy and safety of methoxyflurane in patients with ACS. The study population will comprise patients with ST-elevation myocardial infarction or non-ST-elevation ACS admitted to the study centres with typical chest pain requiring analgesic treatment. Before percutaneous coronary intervention (PCI) for the patients with index ACS will be randomly assigned in 1:1 ratio to receive methoxyflurane administered by inhalation, or to obtain morphine administered intravenously. Analgesic treatment will be followed by 300 mg loading dose of aspirin and 180 mg loading dose of ticagrelor. Patients will be assessed with regard to pain intensity according to the Numeric Pain Rating Scale at baseline, 3 min after study drug administration and immediately after PCI. Moreover, patients will be actively monitored with regard to the occurrence of side effects of evaluated therapies, as well as adverse events that may be related to insufficient platelet inhibition (no-reflow phenomenon assessed immediately after PCI, administration of GPIIb/IIIa inhibitors during PCI, acute stent thrombosis). ETHICS AND DISSEMINATION: The study will be conducted in six Polish clinical centres from the beginning of in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. TRIAL REGISTRATION DETAILS: ClinicalTrials.gov, NCT04476173.

E-selectin gene haplotypes are associated with the risk of myocardial infarction.

INTRODUCTION: Endothelial dysfunction is one of the most important factors implicated in the pathogenesis of coronary artery disease (CAD). The aim of this study was to investigate the association of the E-selectin gene (SELE) with CAD and CAD-related traits using tagging polymorphisms. MATERIAL AND METHODS: A total of 379 Polish patients who had undergone angiography were included: 261 patients with angiographically documented CAD, 202 CAD patients without myocardial infarction (CAD/MI(-) group) and 59 patients with myocardial infarction (CAD/MI(+) group) as well as 118 healthy control subjects (non-CAD). Eight tagging single nucleotide polymorphisms (SNPs) in the SELE gene were selected using genotype data from HapMap. Genotyping was performed using PCR-RFLP and PCR-DHPLC methods. RESULTS: The most common SELE haplotype in this analysis ([C;G;T;C;G;T], 31.2%) showed a negative association with myocardial infarction (MI) (CAD/MI(+) vs. non-CAD) under the additive (p = 0.001), dominant (p = 0.006) and recessive (p = 0.012) model. Two other haplotypes ([C;G;C;C;A;C], [C;A;C;A;G;T], 5.73% and 18.1%, respectively) were also negatively associated with MI under the additive and dominant model. We also found two haplotypes ([T;G;T;C;G;T], [C;G;C;C;A;T], 1.52% and 6.71%, respectively) associated with the risk for MI (CAD/MI(+) vs. CAD/MI(-)), acting in both additive (p = 0.04, p = 0.007, respectively) and dominant (p = 0.04, p = 0.004, respectively) manner. There was no association with either CAD/MI(-) or with severity of CAD expressed as the number of vessels involved. CONCLUSIONS: Our results suggest that SELE is one of the independent genetic factors modifying the risk of myocardial infarction.

Treatment of patients with acute coronary syndrome: Recommendations for medical emergency teams: Focus on antiplatelet therapies. Updated experts' standpoint.

A group of Polish experts in cardiology and emergency medicine, encouraged by the European Society of Cardiology (ESC) guidelines, have recently published common recommendations for medical emergency teams regarding the pre-hospital management of patients with acute coronary syndrome. Due to the recent publication of the 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation and 2017 focused update on dual antiplatelet therapy in coronary artery disease the current panel of experts decided to update the previous standpoint. Moreover, new data coming from studies presented after the previous document was issued were also taken into consideration.

Angiographic severity of coronary artery disease and cardiovascular risk in acute coronary syndrome in patients with metabolic syndrome.

BACKGROUND: The extent of angiographic lesions, size of infarct, and in-hospital and long-term prognosis in patients with metabolic syndrome (MS) have not been clearly determined. AIM: The aim of the study was to investigate the effect of MS on the severity of coronary artery disease (CAD) and cardio-vascular risk evaluated using the GRACE 2.0 risk score and left ventricular ejection fraction (LVEF) in patients with first acute coronary syndrome (ACS) treated with coronary angioplasty. METHODS: The study was conducted in a group of 160 consecutive patients hospitalised for their first ACS. Coronary angiogra-phy was assessed and an echocardiographic evaluation of LVEF was performed. MS was diagnosed according to the National Cholesterol Education Programme-Adult Treatment Panel III criteria. Cardiovascular risk was evaluated using the GRACE 2.0 score. Statistical analysis was performed using the STATISTICA software version 12.0. RESULTS: Diagnostic criteria for MS were met by 53.5% of the patients. Patients with and without MS did not differ in angio-graphic severity of CAD and cardiovascular risk as evaluated with the GRACE 2.0 score. LVEF was significantly elevated in patients with MS. In the examined group the angiographic severity of CAD correlated positively with age, body mass index (BMI) and the homeostatic model assessment for insulin resistance (HOMA-IR) index. The cardiovascular risk correlated positively with age, BMI, fasting insulin levels, and HOMA-IR, and inversely with blood pressure and triglyceride levels. The multivariable regression model for predicting the LVEF value indicated that the strongest prognostic factor was the type of ACS. CONCLUSIONS: The associations between the angiographic severity of CAD and age, BMI, and insulin resistance (IR) confirm the involvement of these parameters in coronary atherosclerosis. The correlations between the estimated cardiovascular risk and IR indicate the prognostic value of metabolic parameters in patients after first ACS. The type of ACS is the strongest predictor of LVEF at discharge in this population.

Variability of platelet response to clopidogrel is not related to adverse cardiovascular events in patients with stable coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND: Antiplatelet response to clopidogrel and its influence upon the risk of cardiovascular adverse events among patients with stable coronary artery disease undergoing percutaneous coronary intervention (PCI) has not been investigated fully. METHODS: Two hundred eleven patients treated with aspirin and clopidogrel were included in the study. Immediately before PCI, residual platelet reactivity testing with impedance aggregometry assay and a single-nucleotide polymorphism genotyping analysis targeting variants of CYP2C19, ABCB1, and PON1 genes was performed. After the index PCI, the patients were screened for cardiovascular events 6 months following bare-metal stent implantation or 12 months following drug-eluting stent implantation. RESULTS: High on-treatment platelet reactivity (HTPR) was observed in 19.43% individuals and low-TPR (LTPR) in 26.54%. In multivariate analysis, HTPR was significantly (p < 0.05) associated with a history of diabetes, higher systolic blood pressure, and platelet count comparing to that of other patients. LTPR was significantly associated with no history of hypertension, younger age, lower platelet count, absence of the CYP2C19*2 variant, and lower CRP plasma level. Overall, cardiac adverse events were noted in 14.23% patients. Survival analysis with the Cox proportional hazard model showed no influence of residual platelet reactivity during clopidogrel therapy upon both ischemic and hemorrhagic events. However, significant predictors for composite of major adverse cardiac events and hospitalization for cardiovascular causes were identified (the higher CCS class prior to coronary intervention and the higher creatinine serum concentration). CONCLUSIONS: The platelet response to clopidogrel has no impact upon post-procedural adverse events at mid-term follow-up in patients with stable CAD undergoing PCI. This finding suggests that routine platelet reactivity testing is not beneficial in this group of patients.