What Can We Learn from the Scalp Hair's Trace Element Content? The Relationship with the Advancement of Coronary Artery Disease.

Background: Multiple risk factors for coronary artery disease have been identified without answering one of the leading questions related to the extent of the involvement of the epicardial arteries. Trace elements are involved in various stages of atherosclerotic lesion formation and may play a significant role in the advancement of coronary artery disease. Methods: A total of 157 (92 (59%) men and 65 (41%) women) patients with a median age of 71 (65-75) years presenting with chronic coronary syndrome were enrolled in the prospective single-center analysis. The coronary angiography results were compared with the concentration of trace elements in scalp hair. Results: Through Spearman analysis, a positive correlation between the number of diseased coronary arteries and hair trace element concentration was found for sodium (r = 0.198, p = 0.013), vanadium (r = 0.164, p = 0.040), chromium (r = 0.242, p = 0.002), and nickel (r = 0.176, p = 0.026). A negative relationship was noted between magnesium (r = -0.237, p = 0.003) and calcium (r = -0.217, p = 0.007) and the extent of epicardial lesions. Conclusions: Scalp hair trace element analysis indicates the possible modulatory role of trace elements in advancing coronary artery disease. Since a significant correlation with one- and two-vessel but not with three-vessel disease was noted, it might be considered an "all or nothing" phenomenon. A positive correlation between the number of diseased coronary arteries and sodium, vanadium, chromium, and nickel and an inverse correlation with magnesium and calcium were noted. The presented analysis is hypothesis-generating, and further studies are necessary to corroborate the results from a clinical perspective.

Neutrophil Extracellular Trap Formation in Advanced Heart Failure Patients-Preliminary Report.

In end-stage heart failure, which is characterized by persistent or progressive ventricular dysfunction despite optimal medical therapy, a left ventricular assist device (LVAD) can be beneficial. Congestive heart failure provokes inflammatory and prothrombotic activation. The aim of this study was to evaluate the serum concentration of citrullinated histone 3 (CH3) representing neutrophil extracellular trap (NET) formation in patients referred for LVAD implantation. There were 10 patients with a median age of 61 (57-65) years enrolled in a prospective single-center analysis who underwent LVAD implantation. The CH3 plasma concentration was measured preoperatively and on the 1st and 7th postoperative days, followed by control measurements on the median (Q1-3) 88th (49-143) day. The preoperative CH3 concentration strongly correlated with brain natriuretic peptide (r = 0.879, p < 0.001). Significant differences in CH3 serum concentration were observed between pre- and postoperative measurements, including an increase on the first postoperative day (p < 0.001), as well as a decrease on the seventh day (p = 0.016) and in follow-up (p < 0.001). CH3 concentration, as a marker of NET formation, decreases after LVAD implantation.

Are Hair Scalp Trace Elements Correlated with Atherosclerosis Location in Coronary Artery Disease?

Coronary artery disease is among the leading current epidemiological challenges. The genetic, clinical, and lifestyle-related risk factors are well documented. The reason for specific epicardial artery locations remains unsolved. The coronary artery topography and blood flow characteristics may induce local inflammatory activation. The atherosclerotic plaque formation is believed to represent inflammatory response involving enzymatic processes co-factored by trace elements. The possible relation between trace elements and coronary artery disease location was the subject of the study. There were 175 patients (107 (61) men and 68 (39) females) in a median (Q1-3) age of 71 years (65-76) admitted for coronary angiography due to chronic coronary syndrome. The angiographic results focused on the percentage of lumen stenosis in certain arteries and were compared with the results for hair scalp trace elements. The correlation between left main coronary artery atherosclerotic plaques and nickel (Ni), zinc (Zn), and antimony (Sb) hair scalp concentration was noted. The analysis revealed a positive relation between left descending artery disease and chromium (Cr), sodium (Na), arsenic (As), and molybdenum (Mo) and a negative correlation with strontium (Sr). The atherosclerotic lesion in the circumflex artery revealed correlations in our analysis with sodium (Na), potassium (K), chromium (Cr), nickel (Ni), arsenic (As), and negative with strontium (Sr) (r) hair scalp concentrations. The negative correlations between right coronary artery disease and magnesium (Mg) and strontium (Sr) concentrations were noted. The possible explanation of different epicardial artery involvement and severity by atherosclerotic processes may lay in their topography and blood rheological characteristics that induce different inflammatory reactions co0factored by specific trace elements. The trace element concentration in the hair scalp may correlate with a particular coronary atherosclerotic involvement, including the severity of lumen reduction. This may indicate the missing link between the pathophysiological processes of atherosclerosis development and its location in coronary arteries.

Long-Term Survival after Coronary Artery Surgical Revascularization-Does Ambient Temperature Matter?

Background and Objectives: The progression of global warming results in an increased exposure to extreme heat, leading to exaggeration of preexisting diseases and premature deaths. The aim of the study was to present possible risk factors for all-cause long-term mortality in patients who underwent surgical revascularization, including an assessment of the influence of ambient temperature exposure. Materials and Methods: Retrospective analysis included 153 (123 (80%) males and 30 (20%) females) patients who underwent off-pump revascularization and were followed for a median time of 2533 (1035-3250) days. The demographical, clinical data and ambient temperature exposure were taken into analysis for prediction of all-cause mortality. Individual exposure was calculated based on the place of habitation. Results: In the multivariate logistic regression model with backward stepwise elimination method, risk factors such as dyslipidaemia (p = 0.001), kidney disease (p = 0.005), age (p = 0.006), and body mass index (p = 0.007) were found to be significant for late mortality prediction. In addition to traditional factors, environmental characteristics, including tropical nights (p = 0.043), were revealed to be significant. Conclusions: High night-time ambient temperatures known as tropical nights may be regarded as additional long-term mortality risk factor after surgical revascularization.

Long-Term Nitrogen Dioxide Exposure as a Possible 5-Year Mortality Risk Factor in Diabetic Patients Treated Using Off-Pump Surgical Revascularization-A Retrospective Analysis.

Background: There is mounting evidence that diabetic-related cardiac metabolism abnormalities with oxidative stress and inflammatory mechanism activation align with the functional impairments that result in atherosclerotic lesion formation. Among the possible non-traditional coronary lesion risk factors, environmental exposure may be significant, especially in diabetic patients. Methods: A total of 140 diabetic patients (115 (82%) males and 25 (18%) females) with a mean age of 65 (60-71) underwent surgical revascularization due to multivessel coronary disease. The possible all-cause mortality risk factors, including demographical and clinical factors followed by chronic air pollution exposure, were identified. Results: All patients were operated on using the off-pump technique and followed for 5.6 (5-6.1) years. The multivariable model for 5-year mortality prediction presented the nitrogen dioxide chronic exposure (HR: 3.99, 95% CI: 1.16-13.71, p = 0.028) and completeness of revascularization (HR: 0.19, 95% CI: 0.04-0.86, p = 0.031) as significant all-cause mortality risk factors. Conclusions: Ambient air pollutants such as an excessive chronic nitrogen dioxide concentration (>15 µg/m3) may increase 5-year all-cause mortality in diabetic patients following surgical revascularization.

Randomised, double-blind, placebo-controlled study evaluating the effect of allopurinol on the risk of cardiovascular events in patients with high and very high cardiovascular risk, including the presence of long-COVID-19 syndrome: the ALL-VASCOR study protocol.

INTRODUCTION: Numerous studies, but not all, have suggested a positive effect of allopurinol on the cardiovascular system. The randomised, double-blind, placebo-controlled study evaluating the effect of allopurinol on the risk of cardiovascular events in patients with high and very high cardiovascular risk, including the presence of long-COVID-19 syndrome (ALL-VASCOR) study aims to evaluate the efficacy of allopurinol therapy for improving cardiovascular outcomes in patients at high and very high cardiovascular risk excluding ischaemic heart disease. This is particularly important due to the high cost of cardiovascular disease treatment and its status as one of the leading causes of mortality. METHODS AND ANALYSIS: The ALL-VASCOR study is a randomised, double-blind, placebo-controlled, multicentre trial that examines the effect of allopurinol therapy (200-500 mg of allopurinol daily) versus an equivalent dose of placebo on the risk of cardiovascular events in 1116 patients aged 40-70 with serum uric acid levels above 5 mg/dL at high and very high risk of cardiovascular disease. The ALL-VASCOR study will also assess the occurrence of long-COVID-19 syndrome. The study will measure primary and secondary as well as additional endpoints and the planned intervention will end on 31 July 2028 unless advised otherwise by the Safe Monitoring Board or other applicable authorities. Participant recruitment is planned to begin in March 2024 in Poland. ETHICS AND DISSEMINATION: The study was ethically approved by the Bioethics Committee of Poznan University of Medical Sciences (No 03/23, 12 January 2023). The results are expected after 2028 and will be disseminated in peer-reviewed journals and at international conferences. PROTOCOL VERSION NUMBER: 01-15 November 2022. TRIAL REGISTRATION NUMBER: EudraCT: 2022-003573-32, 27 October 2022, ClinicalTrials: NCT05943821, 13 July 2023.

Assessment of COVID-19 risk factors of early and long-term mortality with prediction models of clinical and laboratory variables.

BACKGROUND: Coronavirus disease (COVID-19) may lead to serious complications and increased mortality. The outcomes of patients who survive the early disease period are burdened with persistent long-term symptoms and increased long-term morbidity and mortality. The aim of our study was to determine which baseline parameters may provide the best prediction of early and long-term outcomes. METHODS: The study group comprised 141 patients hospitalized for COVID-19. Demographic data, clinical data and laboratory parameters were collected. The main study endpoints were defined as in-hospital mortality and 1-year mortality. The associations between the baseline data and the study endpoints were evaluated. Prediction models were created. RESULTS: The in-hospital mortality rate was 20.5% (n = 29). Compared with survivors, nonsurvivors were significantly older (p = 0.001) and presented comorbidities, including diabetes (0.027) and atrial fibrillation (p = 0.006). Assessment of baseline laboratory markers and time to early death revealed negative correlations between time to early death and higher IL-6 levels (p = 0.032; Spearman rho - 0.398) and lower lymphocyte counts (p = 0.018; Pearson r -0.438). The one-year mortality rate was 35.5% (n = 50). The 1-year nonsurvivor subgroup was older (p < 0.001) and had more patients with arterial hypertension (p = 0.009), diabetes (p = 0.023), atrial fibrillation (p = 0.046) and active malignancy (p = 0.024) than did the survivor subgroup. The model composed of diabetes and atrial fibrillation and IL-6 with lymphocyte count revealed the highest value for 1-year mortality risk prediction. CONCLUSIONS: Diabetes and atrial fibrillation, as clinical factors, and LDH, IL-6 and lymphocyte count, as laboratory determinants, are the best predictors of COVID-19 mortality risk.

Demographical and Clinical Factors Predictive for Aortic Dilatation. When should we be Concerned about the Size?

Background: Thoracic aortic aneurysms are often an accidental finding and result from a degenerative process. Medical therapy includes pharmacological control of arterial hypertension and smoking cessation, that slows the growth of aneurysms. An association between the dilatation of the ascending and abdominal aorta has been already reported. The aim of the study was to identify possible demographic and clinical factors that may implicate further imaging diagnostics in patients with ascending aorta dilatation. Methods: There were 181 (93 (53%) males and 88 (47%) females) patients with a median age of 54 (41-62) years who underwent cardiac magnetic resonance due to non-vascular diseases, were enrolled into retrospective analysis. Results: Multivariable analysis revealed ascending aorta dilatation (odds ratios (OR) = 7.45, 95% confidence interval (CI): 1.98-28.0, p = 0.003) and co-existence of coronary artery disease (OR = 8.68, 95% CI: 2.15-35.1, p = 0.002) as significant predictors for thoracic descending aorta dilatation. In patients with abdominal aorta dilatation, the multivariable analysis showed a predictive value of ascending aortic dilatation (OR = 14.8, 95% CI: 2.36-92.8, p = 0.004) and age (OR = 1.04, 95% CI: 1.00-1.08, p = 0.027). In addition, cut-off values were established for age groups determining the risk of thoracic aorta dilatation over 49 years and abdominal aorta dilatation over 54 years. Conclusions: The results of our analysis showed predictive factors, including ascending aorta dilatation and co-existence of coronary artery disease, particularly over 49 years of age for thoracic, while ascending aorta dilatation and age, particularly over 54 years, for abdominal aorta dilatation. These features may be considered to increase clinical vigilance in patients with aortic diameter abnormalities.

Left main coronary artery disease treated with beating heart surgery: 10-year single center results.

Introduction: Left main (LM) coronary disease is believed to represent a complex, advanced, and potentially life-threatening atherosclerotic syndrome that can be treated by either percutaneous or surgical interventions. Despite its satisfactory results, the declined number of off-pump coronary artery bypass grafting (OPCAB) is observed. Aim: To compare 10-year survival and point out possible mortality risk factors in patients referred for left main and multivessel OPCAB surgery followed by transit time bypass measurements. Material and methods: There were 159 patients (128 (81%) men and 31 (19%) women) in a median age of 66 (60-70) years enrolled in retrospective analysis who were referred to surgical intervention due to left main (51, 32%) and multivessel (108, 68%) disease. The regression analysis for long-term mortality risk and the Kaplan-Meyer survival curve were analyzed. Results: Multivariable analysis pointed female sex (HR = 1.08, 95% CI: 1.03-1.14, p = 0.001) and diabetes mellitus (HR = 6.33, 95% CI: 1.86-21.52, p = 0.003) as possible risk factors for 10-year mortality risk. There was no significant difference in Kaplan-Meyer 10-year mortality comparison between left main and multivessel disease patients treated by off-pump surgical revascularization (HR = 0.93, 95% CI: 0.40-2.13, p = 0.86). Conclusions: Off-pump surgery in the left main disease, compared to multivessel disease, represents a safe surgical technique with satisfactory long-term results. The female sex and diabetes mellitus were found as possible risk factors for 10-year mortality risk in multivariable analysis.

Coronary artery culprit lesions progression and ambient temperature exposure - personalised analysis.

Introduction: Global warming is claimed to be an important cardiovascular disease risk factor. The air pollution and ambient temperatures are believed to have a significant influence on increased morbidity and premature deaths. Aim: To point out possible causative factors for coronary angiography progression in patients presenting with chronic coronary syndrome. Material and methods: There were 66 patients (41 [62%] men and 25 [38%] women) with a median age of 71.5 (62-76) years, who underwent repeated coronary angiographies due to chronic coronary syndrome within a median time interval of 145 (96-296) days. In 18 (27%) patients coronary artery lesion progression was observed despite optimal pharmacotherapy. The demographical, clinical, and personalised epidemiological factors including air pollution particles and ambient temperature exposure were taken into account in the analysis. Results: In the multivariate logistic regression model with backward stepwise elimination method, tropical nights (p = 0.047) and mean daily temperatures (p = 0.043) were revealed as predictors of coronary lesion progression > 30%. The analysis of seasonal temperature changes showed significant differences related to minimal winter temperatures between both groups (p = 0.018). Conclusions: Coronary artery lesion progression can be related to either high values of daily temperatures or to low ambient temperature. The dichotomous characteristics of temperature exposure to atherosclerosis progression suggest a detrimental role of environmental extremities on human health.

Alterations of receptors and insulin-like growth factor binding proteins in senescent cells.

The knowledge about cellular senescence expands dynamically, providing more and more conclusive evidence of its triggers, mechanisms, and consequences. Senescence-associated secretory phenotype (SASP), one of the most important functional traits of senescent cells, is responsible for a large extent of their context-dependent activity. Both SASP's components and signaling pathways are well-defined. A literature review shows, however, that a relatively underinvestigated aspect of senescent cell autocrine and paracrine activity is the change in the production of proteins responsible for the reception and transmission of SASP signals, i.e., receptors and binding proteins. For this reason, we present in this article the current state of knowledge regarding senescence-associated changes in cellular receptors and insulin-like growth factor binding proteins. We also discuss the role of these alterations in senescence induction and maintenance, pro-cancerogenic effects of senescent cells, and aging-related structural and functional malfunctions.

The Protective Effect of the Crosstalk between Zinc Hair Concentration and Lymphocyte Count-Preliminary Report.

BACKGROUND: An imbalance between pro- and anti-inflammatory mechanisms is indicated in the pathophysiology of atherosclerotic plaque. The coronary artery and carotid disease, despite sharing similar risk factors, are developed separately. The aim of this study was to analyze possible mechanisms between trace element hair-scalp concentrations and whole blood counts that favor atherosclerotic plaque progression in certain locations. METHODS: There were 65 (36 (55%) males and 29 (45%) females) patients with a median age of 68 (61-73) years enrolled in a prospective, preliminary, multicenter analysis. The study group was composed of 13 patients with stable coronary artery disease (CAD group) referred for surgical revascularization due to multivessel coronary disease, 34 patients with carotid artery disease (carotid group) admitted for vascular procedure, and 18 patients in a control group (control group). RESULTS: There was a significant difference between the CAD and carotid groups regarding lymphocyte (p = 0.004) counts. The biochemical comparison between the coronary and carotid groups revealed significant differences regarding chromium (Cr) (p = 0.002), copper (Cu) (p < 0.001), and zinc (Zn) (p < 0.001) concentrations. Spearman Rank Order Correlations between lymphocyte counts and trace elements in the analyzed groups were performed, revealing a strong correlation with zinc (R = 0.733, p < 0.001) in the control group (non-CAD, non-carotid). CONCLUSION: Significant differences in hair-scalp concentrations related to atherosclerosis location were observed in our analysis. The interplay between zinc concentration and lymphocyte count may play a pivotal role in cardiovascular disease development.

The Interplay between Dyslipidemia and Neighboring Developments in Coronary Artery Disease Progression: A Personalized Approach.

(1) Background: Estimates suggest that up to 10% of global annual cardiovascular deaths could be related to environmental factors. Not only air pollution components, but also noise exposure and climate changes, are highlighted as nontraditional causes of cardiovascular morbidity. The aim of this study was to identify possible urbanization risk factors for the progression of coronary artery disease in a group of patients with chronic coronary syndrome. (2) Method: There were 77 patients (50 (65%) males and 27 (35%) females) with a median age of 70 (60-74) years who underwent repetitive angiography due to chronic coronary syndrome between 2018 and 2022. The Gensini score was calculated for assessment of coronary artery disease advancement. Environmental factors including neighboring developments were taken into account in this analysis, including housing, commercial, and industrial developments within 300, 500, and 700 m distances (buffer) from the place of habitation. (3) Results: The multivariable analysis results for prediction of Gensini score progression in relation to 700 m buffer urbanization pointed out the significance of hyperlipidemia (OR: 4.24, 95% CI 1.34-13.39, p = 0.014), initial Gensini score (OR: 1.02, 95% CI 1.00-1.05, p = 0.112), and neighborhood housing (OR: 0.03, 95% CI 0.01-0.49, p = 0.025). (4) Conclusions: Hyperlipidemia and housing neighborhood can be regarded as possible factors for coronary disease progression in patients with chronic coronary syndrome with the use of optimal medical therapy.

Anisocytosis as a possible predictor of low cardiac output syndrome in children undergoing mitral valve surgery.

PURPOSE: Mitral valve surgery in children involves correcting congenital and acquired pathologies, with a reported mortality rate of 0.9%. Low cardiac output syndrome (LCOS) is a serious complication with the incidence of 20-25%. The aim of the study was to estimate possible prognostic factors of LCOS in children undergoing mitral valve procedure. MATERIAL AND METHOD: This single-center retrospective analysis enrolled children aged <18 years who underwent mitral valve surgery during 24 year period. Preoperative clinical and laboratory parameters, and operative factors were analyzed. RESULTS: Thirty consecutive pediatric patients (11 (37%) males and 19 (63%) females) in median (Q1 - Q3) age of 57 (25-115) months, who underwent mitral valve replacement, were included. The 30-day mortality was 7% (2 patients) and was related to postoperative multiorgan failure. LCOS occurred in 8 (27%) children. The receiver operator curve (ROC) analysis established parameters that have predictive value for LCOS occurrence: cardiopulmonary bypass (CPB) time, with 89 â€‹min as optimal cut-off point (AUC â€‹= â€‹0.744, p â€‹= â€‹0.011) yielding sensitivity of 100% and specificity of 42.9%; left ventricular ejection fraction (LVEF) â€‹< â€‹60 % (AUC â€‹= â€‹0.824, okp â€‹= â€‹0.001) with sensitivity of 62.5% and specificity of 93.75%; and red blood cell distribution width (RDW) above 14.5 % (AUC â€‹= â€‹0.840, p â€‹< â€‹0.001; sensitivity of 87.5% and specificity of 75%). CONCLUSIONS: In mitral valve replacement in pediatric patients, CPBtime above 89 â€‹min, preoperative LVEF below 60% and preoperative RDW above 14.5% can be regarded as the potential predictors of LCOS.

Comprehensive proteomics of monocytes indicates oxidative imbalance functionally related to inflammatory response in chronic kidney disease-related atherosclerosis.

Atherosclerosis-induced cardiovascular events are the leading cause of mortality in chronic kidney disease (CKD) patients. Monocytes are involved in the formation of atherosclerotic plaques and mediate in the overproduction of ROS, promoting inflammation and oxidative stress. However, the relationship between monocytes, inflammation, and oxidative status in CKD-associated atherosclerosis has not been thoroughly investigated. Monocytes and plasma derived from two groups of CKD patients with varying degrees of atherosclerosis and two groups of patients with cardiovascular disease (CVD) and non-CKD atherosclerosis were analyzed. This study was designed to perform a comprehensive proteomic analysis of monocytes in combination with functional bioinformatics. In addition, a targeted investigation of oxidative stress- and inflammatory-related factors to explore CKD-associated atherosclerosis was applied. Dysregulation of proteins involved in lipid oxidation, cell survival, ROS synthesis and metabolism, and inflammatory responses has been revealed. The characteristic disturbances in the monocyte proteome changed with the progression of CKD. A closer examination of oxidative stress's triggers, mediators, and effects on protein and lipid levels showed alterations in the oxidative imbalance between CKD and CVD. CKD monocytes demonstrated a significant increase of oxidized glutathione without changing the level of its reduced form. Evaluation of enzymatic antioxidants, sources of ROS, and modifications caused by ROS also revealed significant alterations between the study groups. In CKD, inflammation and oxidative imbalance correlated and drove each other. However, in CVD, oxidative stress-related factors were associated with each other but not to inflammatory proteins. Moreover, lipid abnormalities were more specific to classical CVD and unrelated to CKD. Such a comprehensive characterization of monocytes and oxidative stress in CKD and CVD patients has never been presented so far. Obtained results support the involvement of distinct mechanisms underlying the acceleration of atherosclerotic and non-atherosclerotic CKD.

Obesity in Hypertensive Patients Is Characterized by a Dawn Phenomenon in Systolic Blood Pressure Values and Variability.

One of the causes of hypertension is excess weight gain, which can also affect the course of this disease. Both the diagnosis and management of hypertension commonly use ambulatory blood pressure monitoring; the results of which correlate more strongly with cardiovascular diseases and cardiovascular death than office blood pressure monitoring. We evaluated blood pressure values and their variability from hour to hour to see if and when they differed between hypertensive patients with and without obesity. The study included 1345 patients who underwent 24 h ambulatory blood pressure monitoring and then were divided into groups according to body mass index and waist circumference. The obtained data were analyzed according to the subjects' wake-up time, and short-term blood pressure variability parameters were calculated as the mean of the absolute values of the differences between consecutive measurements. The systolic blood pressure in obese subjects was significantly higher between 1 and 5 h before waking than in normal-weighted individuals. In turn, the variability in systolic and diastolic blood pressure was higher with increasing body mass index. The difference in systolic blood pressure values and blood pressure variability was most prominent in the last 5 h of sleep in obese patients.

Decreased toll-like receptor 4 and CD11b/CD18 expression on peripheral monocytes of hypertensive patients correlates with a lesser extent of endothelial damage: a preliminary study.

BACKGROUND: Low-grade chronic inflammation is recognized to contribute to the physiopathology of arterial hypertension. Therefore, this study aimed to assess the pro-inflammatory phenotype of peripheral monocytes of hypertensive patients by analyzing Toll-like receptor 4 (TLR4) and CD11b/CD18 surface expression. In the second part, the influence of phenotypic alterations of monocytes on the endothelial status reflected by circulating endothelial cells (CECs) was evaluated. PATIENTS: The study included 60 patients with arterial hypertension, who were divided into two subgroups based on the disease severity according to the applicable criteria. The mild hypertension and resistant hypertension groups included 30 patients each. The control group consisted of 33 normotensive volunteers matched for age and sex. RESULTS: Both in the entire group of patients and individual subgroups, reduced surface expression of TLR4 and CD11b/CD18 was found compared to normotensive volunteers. A reduced percentage of monocytes with the CD14 + TLR4 + immunophenotype was correlated with a lower MFI level of CD18 and CD11b in the entire group of patients and after division only in the mild hypertension group. Reduced surface expression of TLR4 in hypertensive patients correlated with a lower number of CECs. This relationship was not observed in the resistant hypertension group; instead, an independent effect of reduced CD11b/CD18 expression on the reduction of CEC number was demonstrated. CONCLUSION: Our preliminary study showed for the first time that hypertension of varying severity is accompanied by phenotypic changes in monocytes, manifested by reduced surface expression of both TLR4 and CD11b/CD18. These phenotypic changes were associated with a reduced degree of endothelial injury. Our study opens a new, unexplored area of research on the protective features of peripheral monocytes in hypertension.

Mechanisms of carboplatin- and paclitaxel-dependent induction of premature senescence and pro-cancerogenic conversion of normal peritoneal mesothelium and fibroblasts.

Carboplatin (CPT) and paclitaxel (PCT) are the optimal non-surgical treatment of epithelial ovarian cancer (EOC). Although their growth-restricting influence on EOC cells is well known, their impact on normal peritoneal cells, including mesothelium (PMCs) and fibroblasts (PFBs), is poorly understood. Here, we investigated whether, and if so, by what mechanism, CPT and PCT induce senescence of omental PMCs and PFBs. In addition, we tested whether PMC and PFB exposure to the drugs promotes the development of a pro-cancerogenic phenotype. The results showed that CPT and PCT induce G2/M growth arrest-associated senescence of normal peritoneal cells and that the strongest induction occurs when the drugs act together. PMCs senesce telomere-independently with an elevated p16 level and via activation of AKT and STAT3. In PFBs, telomeres shorten along with an induction of p21 and p53, and their senescence proceeds via the activation of ERK1/2. Oxidative stress in CPT + PCT-treated PMCs and PFBs is extensive and contributes causatively to their premature senescence. Both PMCs and PFBs exposed to CPT + PCT fuel the proliferation, migration, and invasion of established (A2780, OVCAR-3, SKOV-3) and primary EOCs, and this activity is linked with an overproduction of multiple cytokines altering the cancer cell transcriptome and controlled by p38 MAPK, NF-κB, STAT3, Notch1, and JAK1. Collectively, our findings indicate that CPT and PCT lead to iatrogenic senescence of normal peritoneal cells, which paradoxically and opposing therapeutic needs alters their phenotype towards pro-cancerogenic. It cannot be excluded that these adverse outcomes of chemotherapy may contribute to EOC relapse in the case of incomplete tumor eradication and residual disease initiation. © 2023 The Pathological Society of Great Britain and Ireland.