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1.
Clin Res Cardiol ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39297941

RESUMO

BACKGROUND: Ferritin is commonly used to evaluate iron stores and guide therapeutic decisions regarding intravenous iron supplementation. However, in the context of AHF, inflammation-driven upregulation of ferritin might disrupt its correlation with iron stores, restricting iron bioavailability and potentially amplifying the inflammatory response. AIM: This study aims to assess the clinical and prognostic associations of ferritin levels in an AHF cohort and to determine whether the prognostic value of ferritin is influenced by the presence of infection, inflammatory activation, and other markers of iron deficiency. METHODS: The association between ferritin and clinical outcomes (180 days) in AHF was evaluated in a cohort of 526 patients from the EDIFICA registry. RESULTS: The median ferritin plasma concentration at admission was 180 pg/mL. Patients with higher ferritin levels at admission were predominantly men, exhibiting a high prevalence of chronic kidney disease and alcohol consumption, and presenting with lower blood pressure and a higher incidence of clinical infection. Higher ferritin levels were associated with increased risk of the composite of heart failure hospitalization or cardiovascular death (Tertile 2: HR 1.75; 95% CI 1.10-2.79; p = 0.017; Tertile 3: HR 1.79; 95% CI 1.08-2.97; p = 0.025), independently of classical HF prognostic factors, inflammatory and iron-related markers. No significant associations were found between admission serum iron or transferrin saturation tertiles, iron status categories, or guideline-defined iron deficiency (ID) criteria and the primary composite outcome. However, at discharge, patients who met the criteria for defective iron utilization, low iron storage, or guideline-defined ID had a lower risk of the composite endpoint compared to those with normal iron utilization or who did not meet the guideline-defined ID criteria, respectively. CONCLUSIONS: Elevated ferritin levels are independently associated with poor prognosis in AHF. Low ferritin levels are associated with a favorable outcome and do not carry significant value in identifying ID in this population.

2.
Int J Mol Sci ; 25(15)2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39125899

RESUMO

Pericardial fluid (PF) has been suggested as a reservoir of molecular targets that can be modulated for efficient repair after myocardial infarction (MI). Here, we set out to address the content of this biofluid after MI, namely in terms of microRNAs (miRs) that are important modulators of the cardiac pathological response. PF was collected during coronary artery bypass grafting (CABG) from two MI cohorts, patients with non-ST-segment elevation MI (NSTEMI) and patients with ST-segment elevation MI (STEMI), and a control group composed of patients with stable angina and without previous history of MI. The PF miR content was analyzed by small RNA sequencing, and its biological effect was assessed on human cardiac fibroblasts. PF accumulates fibrotic and inflammatory molecules in STEMI patients, namely causing the soluble suppression of tumorigenicity 2 (ST-2), which inversely correlates with the left ventricle ejection fraction. Although the PF of the three patient groups induce similar levels of fibroblast-to-myofibroblast activation in vitro, RNA sequencing revealed that PF from STEMI patients is particularly enriched not only in pro-fibrotic miRs but also anti-fibrotic miRs. Among those, miR-22-3p was herein found to inhibit TGF-ß-induced human cardiac fibroblast activation in vitro. PF constitutes an attractive source for screening diagnostic/prognostic miRs and for unveiling novel therapeutic targets in cardiac fibrosis.


Assuntos
Fibrose , MicroRNAs , Infarto do Miocárdio , Líquido Pericárdico , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Masculino , Líquido Pericárdico/metabolismo , Feminino , Miocárdio/metabolismo , Miocárdio/patologia , Pessoa de Meia-Idade , Fibroblastos/metabolismo , Idoso , Fator de Crescimento Transformador beta/metabolismo , Infarto do Miocárdio com Supradesnível do Segmento ST/metabolismo , Infarto do Miocárdio com Supradesnível do Segmento ST/patologia , Infarto do Miocárdio com Supradesnível do Segmento ST/genética , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Proteína 1 Semelhante a Receptor de Interleucina-1/genética
3.
Eur J Cardiothorac Surg ; 65(5)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38688560

RESUMO

OBJECTIVES: Patients with severe coronary artery disease who undergo coronary artery bypass grafting consistently demonstrate that continued smoking after surgery increases late mortality rates. Smoking may exert its harmful effects through the ongoing chronic process of atherosclerotic progression both in the grafts and the native system. However, it is not clear whether cardiac mortality is primary and solely responsible for the inferior late survival of current smokers. METHODS: In this retrospective analysis, we included all consecutive patients undergoing primary isolated coronary artery bypass surgery from 1 January 2000 to 30 September 2015 in an Academic Hospital in Northern Portugal. The predictive or independent variable was the patients' smoking history status, a categorical variable with 3 levels: non-smoker (the comparator), ex-smoker for >1 year (exposure 1) and current smoker (exposure 2). The primary end point was long-term all-cause mortality. Secondary outcomes were long-term cause-specific mortality (cardiovascular and noncardiovascular). We fitted overall and Fine and Gray subdistribution hazard models. RESULTS: We identified 5242 eligible patients. Follow-up was 99.7% complete (with 17 patients lost to follow-up). The median follow-up time was 12.79 years (interquartile range, 9.51-16.60). Throughout the study, there were 2049 deaths (39.1%): 877 from cardiovascular causes (16.7%), 727 from noncardiovascular causes (13.9%) and 445 from unknown causes (8.5%). Ex-smokers had an identical long-term survival than non-smokers [hazard ratio (HR) 0.99; 95% confidence interval (CI) 0.88, 1.12; P = 0.899]. Conversely, current smokers had a 24% increase in late mortality risk (HR 1.24; 95% CI 1.07, 1.44; P = 0.004) as compared to non-smokers. While the current smoker status increased the relative incidence of noncardiac death by 61% (HR 1.61; 95% CI 1.27, 2.05, P < 0.001), it did confer a 25% reduction in the relative incidence of cardiac death (HR 0.75; 95% CI 0.59, 0.97; P = 0.025). CONCLUSIONS: Whereas ex-smokers have an identical long-term survival to non-smokers, current smokers exhibit an increase in late all-cause mortality risk at the expense of an increased relative incidence of noncardiac death. By subtracting the inciting risk factor, smoking cessation reduces the relative incidence of cardiac death.


Assuntos
Ponte de Artéria Coronária , Doença da Artéria Coronariana , Fumar , Humanos , Ponte de Artéria Coronária/mortalidade , Ponte de Artéria Coronária/efeitos adversos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/mortalidade , Fumar/efeitos adversos , Fumar/epidemiologia , Medição de Risco/métodos , Fatores de Risco , Período Pré-Operatório , Portugal/epidemiologia
4.
Free Radic Biol Med ; 218: 68-81, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38574975

RESUMO

Sarcopenia is associated with reduced quality of life and premature mortality. The sex disparities in the processes underlying sarcopenia pathogenesis, which include mitochondrial dysfunction, are ill-understood and can be decisive for the optimization of sarcopenia-related interventions. To improve the knowledge regarding the sex differences in skeletal muscle aging, the gastrocnemius muscle of young and old female and male rats was analyzed with a focus on mitochondrial remodeling through the proteome profiling of mitochondria-enriched fractions. To the best of our knowledge, this is the first study analyzing sex differences in skeletal muscle mitochondrial proteome remodeling. Data demonstrated that age induced skeletal muscle atrophy and fibrosis in both sexes. In females, however, this adverse skeletal muscle remodeling was more accentuated than in males and might be attributed to an age-related reduction of 17beta-estradiol signaling through its estrogen receptor alpha located in mitochondria. The females-specific mitochondrial remodeling encompassed increased abundance of proteins involved in fatty acid oxidation, decreased abundance of the complexes subunits, and enhanced proneness to oxidative posttranslational modifications. This conceivable accretion of damaged mitochondria in old females might be ascribed to low levels of Parkin, a key mediator of mitophagy. Despite skeletal muscle atrophy and fibrosis, males maintained their testosterone levels throughout aging, as well as their androgen receptor content, and the age-induced mitochondrial remodeling was limited to increased abundance of pyruvate dehydrogenase E1 component subunit beta and electron transfer flavoprotein subunit beta. Herein, for the first time, it was demonstrated that age affects more severely the skeletal muscle mitochondrial proteome of females, reinforcing the necessity of sex-personalized approaches towards sarcopenia management, and the inevitability of the assessment of mitochondrion-related therapeutics.


Assuntos
Envelhecimento , Músculo Esquelético , Sarcopenia , Animais , Masculino , Feminino , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Ratos , Envelhecimento/metabolismo , Sarcopenia/metabolismo , Sarcopenia/patologia , Mitocôndrias Musculares/metabolismo , Mitocôndrias Musculares/patologia , Estradiol/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Fibrose/metabolismo , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Proteoma/metabolismo , Fatores Sexuais , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mitofagia
5.
Atherosclerosis ; 390: 117461, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38306764

RESUMO

BACKGROUND AND AIMS: Inflammation is a risk factor for major adverse cardiovascular events (MACE). Elevated levels of both high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL6) have been associated with MACE. However, few studies have compared IL6 to hsCRP for cardiovascular risk assessment. Using the MESA (Multi-Ethnic Study of Atherosclerosis) study cohort, we aim to compare IL6 to hsCRP. METHODS: We divided IL6 and hsCRP by their median values and created 4 groups i.e., low-low, high-low, low-high and high-high. The median follow-up was 14 years. RESULTS: 6614 (97 %) participants had complete baseline IL6 and hsCRP data. The correlation between hsCRP and IL6 was modest (Rho = 0.53). IL6 ≥1.2 pg/mL (median) was present in 3309 participants, and hsCRP ≥1.9 mg/L (median) was present in 3339 participants. Compared to participants with low IL6 and low hsCRP, those with high IL6 and high hsCRP were older (64 vs. 60 years), more frequently women (63 % vs. 45 %), and with more cardiovascular co-morbidities. hsCRP outcome associations lost statistical significance when adjusting for IL6: MACE HR (95 %CI) 1.06 (0.93-1.20), p =0.39, whereas IL6 associations remained significant after adjusting for hsCRP: HR (95 %CI) 1.44 (1.25-1.64), p <0.001. The C-index of Framingham score for did not improve with hsCRP but improved with IL6. Compared to participants with low IL6 and low hsCRP, those with high IL6, regardless of hsCRP, experienced an increased risk of MACE, heart failure and mortality. CONCLUSIONS: In a diverse and asymptomatic population, IL6 showed a stronger association with atherosclerotic, heart failure and fatal outcomes than hsCRP.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Insuficiência Cardíaca , Humanos , Feminino , Proteína C-Reativa/análise , Interleucina-6 , Fatores de Risco , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Aterosclerose/complicações , Medição de Risco , Progressão da Doença , Insuficiência Cardíaca/complicações , Fatores de Risco de Doenças Cardíacas
6.
Proteomics Clin Appl ; 18(3): e2300102, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38169112

RESUMO

PURPOSE: The main objective of this study is to characterize and analyze modified peptides in DBS samples. This includes deciphering their specific PTMs and understanding their potential impact on the population or disease cohort under study. EXPERIMENTAL DESIGN: Using mass spectrometry-based proteomic approaches, we performed a comprehensive analysis of DBS samples. Our focus was on the identification and quantification of modified peptides. We also took advantage of recent advances in DBS mass spectrometry to ensure accurate detection and quantification. RESULTS: A comprehensive analysis identified 972 modified peptides in DBS samples. Of these, a subset of 211 peptides was consistently present in all samples, highlighting their potential biological importance and relevance. This indicates a diverse spectrum of PTMs in the proteome of DBS samples. CONCLUSIONS AND CLINICAL RELEVANCE: Integration of mass spectrometry and proteomics has revealed a broad spectrum of modified peptides in DBS samples and highlighted their importance in biological processes and disease progression. Accurate detection of these PTMs may be critical for risk stratification and disease management. This study improves the understanding of molecular mechanisms underlying biological processes and disease development, providing important insights for clinical applications.


Assuntos
Teste em Amostras de Sangue Seco , Espectrometria de Massas , Processamento de Proteína Pós-Traducional , Proteômica , Humanos , Proteômica/métodos , Teste em Amostras de Sangue Seco/métodos , Peptídeos/sangue , Peptídeos/análise , Proteoma/análise
7.
Eur J Cardiothorac Surg ; 65(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38058180

RESUMO

OBJECTIVES: To compare the independent and combined effects of anaemia and red blood cell transfusion on late survival after isolated coronary artery bypass grafting. METHODS: Retrospective analysis of 5243 consecutive patients undergoing primary isolated coronary artery bypass grafting, performed from 2000 to 2015, in a Portuguese Academic Hospital. We identified 1649 patients with preoperative anaemia (A+) and 1422 patients who received a perioperative transfusion (T+)-the 4 possible combinations allowed for the creation of 4 subgroups (A-/T-, A-/T+, A+/T- and A+/T+). The primary endpoint was all-cause mortality at 10 years. We employed inverse probability weighting to control for confounding variables. RESULTS: Thirty-one percent of the patients had preoperative anaemia, and 27.0% had at least one packed red blood cell transfusion. Inverse probability weighting was effective in eliminating differences in all significant baseline characteristics. The primary endpoint of all-cause mortality at 10 years occurred in 568 patients (20.5%) in the A-/T- group, as compared with 204 (24.4%) in the A-/T+ group (hazard ratio, 1.14; 95% confidence interval, 1.00 to 1.31; P = 0.053), 358 (33.8%) in the A+/T- group (hazard ratio, 1.53; 95% confidence interval, 1.38 to 1.71; P < 0.001), 254 (43.6%) in the A+/T+ group (hazard ratio, 2.25; 95% confidence interval, 1.97 to 2.56; P < 0.001). CONCLUSIONS: This longitudinal, population-level study emphasizes the adverse long-term outcomes of preoperative anaemia and perioperative red blood cell transfusion. It stresses the importance of an evidence-based, multimodal and multidisciplinary approach to conserving blood resources and optimizing outcomes in patients at high risk for transfusion.


Assuntos
Anemia , Ponte de Artéria Coronária , Humanos , Estudos Retrospectivos , Ponte de Artéria Coronária/efeitos adversos , Transfusão de Sangue , Transfusão de Eritrócitos , Anemia/complicações , Anemia/terapia
8.
J Vis Exp ; (200)2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37930007

RESUMO

Large animal models of heart failure play an essential role in the development of new therapeutic interventions due to their size and physiological similarities to humans. Efforts have been dedicated to creating a model of pressure-overload induced heart failure, and ascending aortic banding while still supra-coronary and not a perfect mimic of aortic stenosis in humans, closely resembling the human condition. The purpose of this study is to demonstrate a minimally invasive approach to induce left ventricular pressure overload by placing an aortic band, precisely calibrated with percutaneously introduced high-fidelity pressure sensors. This method represents a refinement of the surgical procedure (3Rs), resulting in homogenous trans-stenotic gradients and reduced intragroup variability. Additionally, it enables swift and uneventful animal recovery, leading to minimal mortality rates. Throughout the study, animals were followed for up to 2 months after surgery, employing transthoracic echocardiography and pressure-volume loop analysis. However, longer follow-up periods can be achieved if desired. This large animal model proves valuable for testing new drugs, particularly those targeting hypertrophy and the structural and functional alterations associated with left ventricular pressure overload.


Assuntos
Estenose da Valva Aórtica , Insuficiência Cardíaca , Humanos , Animais , Suínos , Coração , Insuficiência Cardíaca/etiologia , Estenose da Valva Aórtica/cirurgia , Ecocardiografia , Aorta/cirurgia , Hipertrofia Ventricular Esquerda , Modelos Animais de Doenças
9.
Artigo em Inglês | MEDLINE | ID: mdl-37740299

RESUMO

OBJECTIVES: The aim of this sudy was to investigate the presence of an obesity paradox on the long-term mortality of patients undergoing primary isolated coronary artery bypass surgery and to uncover whether any discrepancy found could be attributable to cardiovascular or noncardiovascular causes. METHODS: Retrospective analysis of 5242 consecutive patients with body mass index (BMI) over 18.5 kg/m2 undergoing primary isolated coronary artery bypass surgery, performed from 2000 to 2015, in a Portuguese level III Hospital. The primary end point was long-term all-cause mortality. Secondary outcomes were long-term cause-specific mortality (cardiovascular and noncardiovascular). We fitted overall, and cause-specific hazard models, with BMI forced both as a categorical (using World Health Organization predefined cutoffs) and as a continuous variable. RESULTS: Follow-up was 99.7% complete. The median follow-up time was 12.79 years (interquartile range, 9.51-16.61). The cumulative incidence functions failed to uncover any difference in 15-year all-cause (log-rank test, P = 0.400), cardiovascular (Gray's test, P = 0.996) and noncardiovascular mortality (Gray's test, P = 0.305) between BMI categories. Likewise, extensive multivariable-adjusted Cox regression and cause-specific hazards models failed to demonstrate in-between category differences, with BMI forced as a categorical variable. On the other hand, using BMI as a continuous variable, the model identified the optimal BMI as between 25.8 and 30.3 kg/m2 (nadir around 28.9 kg/m2), albeit this was dependent on the definition of the reference value. CONCLUSIONS: In this longitudinal, population-level analysis of patients undergoing isolated primary coronary artery bypass grafting, we could not attest to any protective effect of obesity on long-term survival.

10.
Am J Physiol Heart Circ Physiol ; 325(4): H774-H789, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37477690

RESUMO

Pregnant women with cardiovascular risk (CVR) factors are highly prone to develop cardiovascular disease later in life. Thus, recent guidelines suggest extending the follow-up period to 1 yr after delivery. We aimed to evaluate cardiovascular remodeling during pregnancy and determine which CVR factors and potential biomarkers predict postpartum cardiac and vascular reverse remodeling (RR). Our study included a prospective cohort of 76 healthy and 54 obese and/or hypertensive and/or with gestational diabetes pregnant women who underwent transthoracic echocardiography, pulse-wave velocity (PWV), and blood collection at the 1st trimester (1T) and 3rd trimester (3T) of pregnancy as well as at the 1st/6th/12th mo after delivery. Generalized linear mixed-effects models was used to evaluate the extent of RR and its potential predictors. Pregnant women develop cardiac hypertrophy, as confirmed by a significant increase in left ventricular mass (LVM). Moreover, ventricular filling pressure (E/e') and atrial volume increased significantly during gestation. Significant regression of left ventricular (LV) volume, LVM, and filling pressures was observed as soon as 1 mo postpartum. The LV global longitudinal strain worsened slightly and recovered at 6 mo postpartum. PWV decreased significantly from 1T to 3T and normalized at 1 mo postpartum. We found that arterial hypertension, smoking habits, and obesity were independent predictors of increased LVM during pregnancy and postpartum. High C-reactive protein (CRP) and low ST2/IL33-receptor levels are potential circulatory biomarkers of worse LVM regression. Arterial hypertension, age, and gestational diabetes positively correlated with PWV. Altogether, our findings pinpoint arterial hypertension as a critical risk factor for worse RR and CRP, and ST2/IL33 receptors as potential biomarkers of postpartum hypertrophy reversal.NEW & NOTEWORTHY This study describes the impact of cardiovascular risk factors (CVR) in pregnancy-induced remodeling and postpartum reverse remodeling (up to 1 yr) by applying advanced statistic methods (multivariate generalized linear mixed-effects models) to a prospective cohort of pregnant women. Aiming to extrapolate to pathological conditions, this invaluable "human model" allowed us to demonstrate that arterial hypertension is a critical CVR for worse RR and that ST2/IL33-receptors and CRP are potential biomarkers of postpartum hypertrophy reversal.


Assuntos
Doenças Cardiovasculares , Diabetes Gestacional , Hipertensão , Gravidez , Feminino , Humanos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Estudos Prospectivos , Proteína 1 Semelhante a Receptor de Interleucina-1 , Interleucina-33 , Fatores de Risco , Período Pós-Parto , Obesidade/complicações , Obesidade/diagnóstico , Cardiomegalia , Biomarcadores , Fatores de Risco de Doenças Cardíacas
11.
Cancers (Basel) ; 15(14)2023 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-37509381

RESUMO

Hematopoietic stem cell transplant (HSCT) is an important treatment option for hematologic malignancies. Acute kidney injury (AKI) is a common complication in HSCTs and is related to worse outcomes. We aimed to create a predictive risk score for AKI in HSCT considering variables available at the time of the transplant. We performed a retrospective cohort study. AKI was defined by the KDIGO classification using creatinine and urinary output criteria. We used survival analysis with competing events. Continuous variables were dichotomized according to the Liu index. A multivariable analysis was performed with a backward stepwise regression. Harrel's C-Statistic was used to evaluate the performance of the model. Points were attributed considering the nearest integer of two times each covariate's hazard ratio. The Liu index was used to establish the optimal cut-off. We included 422 patients undergoing autologous (61.1%) or allogeneic (38.9%) HSCTs for multiple myeloma (33.9%), lymphoma (27.3%), and leukemia (38.8%). AKI cumulative incidence was 59.1%. Variables eligible for the final score were: hematopoietic cell transplant comorbidity index ≥2 (HR: 1.47, 95% CI: 1.08-2.006; p = 0.013), chronic kidney disease (HR: 2.10, 95% CI: 1.31-3.36; p = 0.002), lymphoma or leukemia (HR: 1.69, 95% CI: 1.26-2.25; p < 0.001) and platelet-to-lymphocyte ratio > 171.9 (HR: 1.43, 95% CI: 1.10-1.86; p = 0.008). This is the first predictive risk score for AKI in patients undergoing HSCTs and the first study where the platelet-to-lymphocyte ratio is independently associated with AKI.

12.
Vascular ; : 17085381231175707, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37217256

RESUMO

OBJECTIVES: Chronic venous disease (CVD) is a prevalent pathology, and endothelial dysfunction is recognized as a core of its physiopathology. Flow-mediated dilation (FMD) is one of the most widely used tests for evaluating endothelial function. The aim of this study is to evaluate the influence of varicose vein (VV) surgery on FMD. METHODS: A prospective study with patients with superficial CVD and saphenous incompetence on Doppler ultrasonography that were proposed for VV surgery. The FMD test was performed before and 6 months after the procedure. The operator performing the post-operative evaluation was blinded to the pre-operative result. RESULTS: A total of 42 patients were included in the analysis. The median pre-operative percent change of FMD was 4.20% (±1.30) and the post-operative was 4.56% (±1.25) (p = 0.819). CONCLUSIONS: Our findings do not corroborate the presence of an overall endothelial dysfunction prone to modulation by surgery. Nevertheless, further studies are needed to confirm our findings.

13.
Mol Biol Rep ; 50(3): 2763-2778, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36583779

RESUMO

Galectin-3 (Gal-3) belongs to galectin protein family, a type of ß-galactose-binding lectin having more than one evolutionarily conserved domain of carbohydrate recognition. Gal-3 is mainly located in the cytoplasm, but it also enters the nucleus and is secreted into the extracellular environment and biological fluids such as urine, saliva, and serum. It plays an important role in many biological functions, such as angiogenesis, apoptosis, cell differentiation, cell growth, fibrosis, inflammation, host defense, cellular modification, splicing of pre-mRNA, and transformation. Many previous studies have shown that Gal-3 can be used as a diagnostic or prognostic biomarker for heart ailments, kidney diseases, and other major illnesses including cancer. Moreover, it may also play a major role in risk stratification in different diseases, and in this review, we have summarized the potential roles and application of Gal-3 as diagnostic, prognostic, and risk stratifying biomarker from previously reported studies in heart diseases and cancer, with special emphasis on prostate cancer.


Assuntos
Cardiopatias , Neoplasias da Próstata , Humanos , Masculino , Biomarcadores , Galectina 3/genética , Galectinas/genética , Cardiopatias/diagnóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo
14.
Int J Mol Sci ; 25(1)2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38203721

RESUMO

The salivary glands play a central role in the secretion of saliva, whose composition and volume affect oral and overall health. A lesser-explored dimension encompasses the possible changes in salivary gland proteomes in response to fluctuations in sex hormone levels. This study aimed to examine the effects of chronic exposure to testosterone on salivary gland remodeling, particularly focusing on proteomic adaptations. Therefore, male Wistar rats were implanted with subcutaneous testosterone-releasing devices at 14 weeks of age. Their submandibular glands were histologically and molecularly analyzed 47 weeks later. The results underscored a significant increase in gland mass after testosterone exposure, further supported by histologic evidence of granular duct enlargement. Despite increased circulating sex hormones, there was no detectable shift in the tissue levels of estrogen alpha and androgen receptors. GeLC-MS/MS and subsequent bioinformatics identified 308 proteins in the submandibular glands, 12 of which were modulated by testosterone. Of note was the pronounced upregulation of Klk3 and the downregulation of Klk6 and Klk7 after testosterone exposure. Protein-protein interaction analysis with the androgen receptor suggests that Klk3 is a potential target of androgenic signaling, paralleling previous findings in the prostate. This exploratory analysis sheds light on the response of salivary glands to testosterone exposure, providing proteome-level insights into the associated weight and histological changes.


Assuntos
Proteoma , Testosterona , Masculino , Ratos , Animais , Glândula Submandibular , Proteômica , Espectrometria de Massas em Tandem , Ratos Wistar , Congêneres da Testosterona
15.
Front Endocrinol (Lausanne) ; 13: 1067801, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36518251

RESUMO

Background: Thyroid hormones are important modulators of cardiovascular function. Both hypothyroidism and hyperthyroidism are known to contribute to an increased cardiovascular risk. It remains uncertain whether thyroid hormones level within the euthyroid range are associated with cardiometabolic risk. We aimed to evaluate the association between thyroid function levels within the euthyroid range and cardiovascular risk in a population-based cohort. Methods: Eight hundred thirty-five subjects aged ≥45 years from the EPIPorto population-based cohort were included. We excluded participants with TSH, free T4 (FT4), or free T3 (FT3) outside of the reference range, or with previous cardiovascular or thyroid disease. The associations between thyroid function, cardiovascular risk factors and the 10-year estimated risk of cardiovascular events (using SCORE2 and SCORE2-OP) were evaluated in linear and logistic regression models, crudely and adjusting for age, sex, BMI, diabetes, and smoking. Results: The mean age of the participants was 61.5 (SD 10.5) years and 38.9% were men. Eleven percent of the participants had diabetes, 47.8% had dyslipidemia, and 54.8% had hypertension. The mean body mass index (BMI) was 27.4 (SD 4.6) kg/m2, and the median (percentile25-75) 10-year risk of cardiovascular events was 5.46% (2.92, 10.11). Participants with higher BMI, larger waist circumference and higher hs-CRP had higher levels of FT3 and FT3/FT4 ratio. Lower FT3/FT4 ratio and higher FT4 levels were associated with higher prevalence of diabetes and more adverse lipid profile. Higher TSH, lower FT3 and lower FT3/FT4 ratio were associated with lower eGFR. Lower FT3, lower FT3/FT4 ratio and higher FT4 were associated with an increased 10-year risk of cardiovascular events. Conclusions: In a population-based study, variations of thyroid function within the euthyroid range were associated with cardiovascular risk factors. On one hand, individuals with higher BMI, larger waist circumference and higher hs-CRP had higher levels of FT3 and FT3/FT4 ratio. On the other hand, a decreased conversion of T4 to T3 (lower FT3, lower FT3/FT4 ratio and/or higher FT4) was associated with a higher prevalence of diabetes, a more adverse lipid profile, a lower eGFR and an increased 10-year risk of cardiovascular events.


Assuntos
Doenças Cardiovasculares , Hipertireoidismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína C-Reativa , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Fatores de Risco de Doenças Cardíacas , Lipídeos , Fatores de Risco , Hormônios Tireóideos , Tireotropina , Idoso
16.
Port J Card Thorac Vasc Surg ; 29(3): 45-50, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36197822

RESUMO

A The recent years of the cardiovascular medicine saw a rapid development of advanced imaging modalities. The new era of personalized medicine takes advantage of what can be interpreted from medical images, searching for underlying connections between image phenotyping and biological characteristics to support precise clinical decisions. The application of radiomics in cardiovascular imaging has lagged behind other fields, such as oncology. While the current interpretation of cardiac and vascular images mainly depends on subjective and qualitative analysis, radiomics uses advanced image analysis to extract numerous quantitative features from digital images that are unrecognizable to the naked eye. The goal of this narrative review is to highlight the main findings of the recent use of radiomic analysis in the cardiovascular field. English-language articles published in the database PubMed were used for this review. The keywords used in the search included radiomics, cardiovascular or cardiac or aortic. Radiomics is expected to contribute to a more precise phenotyping of the cardiovascular disease, which can improve diagnostic, prognostic, and therapeutic decision making in the near future.


Assuntos
Doenças Cardiovasculares , Doenças Cardiovasculares/diagnóstico , Coração , Humanos , Processamento de Imagem Assistida por Computador/métodos , Medicina de Precisão/métodos , Prognóstico
17.
Port J Card Thorac Vasc Surg ; 29(3): 21-27, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36197823

RESUMO

BACKGROUND: It is particularly difficult to choose the appropriate prosthesis to treat infective endocarditis. OBJECTIVES: To investigate the outcomes after aortic valve replacement with a stented bioprosthesis (Trifecta) in patients with active or previous infective endocarditis. METHODS: We performed a single-centre, retrospective study including consecutive patients with infective endocarditis who underwent aortic valve replacement between July 2011 and June 2019. Survival and reintervention were assessed as of December 2021. Hospital mortality was defined as death in-hospital or within 30-days of surgery. Kaplan-Meier method was used for time-to-event outcome assessment (all-cause mortality and reoperation). Data are median (minimum and maximum) or absolute (relative) frequencies. RESULTS: We included 51 patients, median age of 69 (40 to 87) years, 78% male. The median follow-up time was 5.4 years and the maximum was 10 years. Most patients (71%) had native valve infective endocarditis and 16% had previous endocarditis. Surgery was urgent in 82%. Hospital mortality occurred in 10 patients (20%). After excluding these patients, 1-, 3-, 6-, and 9-years cumulative survival rates were 93%, 78%, 72%, and 72%, respectively. There were five bioprosthesis-related reoperations: 4 due to endocarditis at 1-year, 3-years, and 5-years on follow-up (n=1, 1 and 2, respectively) and 1 due to non-structural deterioration, 6-years after surgery. CONCLUSIONS: Despite the small sample size, this report supports a satisfactory performance profile of the Trifecta bioprosthesis in the treatment of infective endocarditis.


Assuntos
Endocardite Bacteriana , Implante de Prótese de Valva Cardíaca , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/cirurgia , Endocardite Bacteriana/etiologia , Feminino , Seguimentos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Masculino , Desenho de Prótese , Estudos Retrospectivos , Fatores de Tempo
18.
PLoS One ; 17(9): e0275035, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36149872

RESUMO

BACKGROUND: Several of the most extensively used risk prediction tools for coronary artery bypass grafting outcomes include female sex as an independent risk factor for postoperative outcomes. It is not clear whether this putative increased surgical risk impacts long-term survival. This study aimed to assess sex differences in 10-year all-cause mortality. METHODS: Retrospective analysis of 5340 consecutive patients undergoing primary isolated coronary artery bypass surgery, performed from 2000 to 2015, in a Portuguese level III Hospital. The primary endpoint was all-cause mortality at ten years. We employed an overlap weighting algorithm to minimize confounding. Its target population highlights patients with the most overlap in their observed characteristics, and its corresponding estimand is the average treatment effect in the overlap population. RESULTS: We identified that 5340 patients underwent isolated CABG: 1104 (20.7%) were female, and 4236 (79.3%) were male. Sixteen patients were lost to follow-up (0.3%). The median follow-up time was 12.79 (IQR, 9.52-16.66) years: 12.68 (IQR, 9.48-16.54) years for the male patient group and 13.13 (IQR, 9.75-16.98) years for the female patient group. The primary endpoint of all-cause mortality at ten years occurred in 1106 patients (26.1%) in the male patient group, compared with 315 (28.5%) in the female patient group. The unweighted survival analysis for both groups reveals the worst long-term prognosis for the female cohort (hazard ratio, 1.22; 95% CI, 1.10 to 1.35; p < 0.001), while in the overlap weighted survival analysis, such long-term difference in prognosis disappears (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; p = 0.693). CONCLUSION: In this longitudinal, population-level analysis of patients undergoing primary, isolated CABG, we demonstrated that the female sex is not associated with increased long-term all-cause mortality compared to their male counterparts. Thus, sex should not influence the undertaking of an adequate revascularization strategy.


Assuntos
Doença da Artéria Coronariana , Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Masculino , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
19.
Cytokine ; 160: 156053, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36179534

RESUMO

AIMS: Interleukin-6 (IL-6) is upregulated in response to infectious and inflammatory triggers and independently predicts all-cause mortality in acute heart failure (AHF). However, the association of IL-6 with cardiovascular outcomes and its interplay with C-reactive protein and infection, a major precipitating factor in AHF, remains poorly understood. METHODS AND RESULTS: The association between IL-6 and clinical outcomes (180 days) in AHF was evaluated using a cohort of 164 patients from the EDIFICA registry. Median IL-6 levels at admission were 17.4 pg/mL. Patients in the higher admission IL-6 tertile presented with lower blood pressure and more congestion, were diagnosed more frequently with infection, and had a longer hospital stay. Higher IL-6 levels were associated with increased risk of HF rehospitalization (hazard ratio per log2 3.69, 95% confidence interval (CI) 1.26-10.8, p =.017) and the composite of HF rehospitalization or cardiovascular death (hazard ratio per log2 3.50; 95% CI 1.28-9.57; p =.014), independently of major AHF prognosticators, including B-type natriuretic peptide and renal function. However, no independent associations were found for all-cause rehospitalization or mortality. Despite a moderate correlation of IL-6 with C-reactive protein (CRP) levels (R = .51), the latter were not associated with clinical outcomes in this population. CONCLUSIONS: IL-6 levels associate with higher rate of cardiovascular events in AHF, independently of classical prognosticators and evidence of infection, outperforming CRP as an inflammatory outcome biomarker.


Assuntos
Insuficiência Cardíaca , Interleucina-6/sangue , Peptídeo Natriurético Encefálico , Doença Aguda , Biomarcadores , Proteína C-Reativa , Humanos , Prognóstico , Sistema de Registros
20.
Artigo em Inglês | MEDLINE | ID: mdl-36005896

RESUMO

OBJECTIVES: As definitive data from randomized controlled trials comparing the effect on long-term survival of using single internal mammary artery (SIMA) or bilateral internal mammary artery (BIMA) grafting are not yet available, observational studies allow for long-term follow-up in large and representative populations, which might complement the information potentially derived from randomized trials. To compare long-term survival in patients under 70 years of age undergoing SIMA or BIMA grafting. METHODS: Retrospective analysis of 3384 consecutive patients under 70 years undergoing primary isolated coronary artery bypass grafting, performed from 2000 to 2015, in a Portuguese level III Hospital. We identified 2176 and 1208 patients from the study population who underwent SIMA and BIMA grafting, respectively. The primary end point was all-cause mortality at 10 years. We employed inverse probability weighting to restrict confounding by indication. RESULTS: The mean age of the study population was 59.4 (± 7.6) years, and 567 (16.8%) were females. Inverse probability weighting was effective in eliminating differences in all significant baseline characteristics. Follow-up was 99.88% complete. The median follow-up time was 12.82 (interquartile range, 9.65, 16.74) years: the primary end point of all-cause mortality at 10 years occurred in 463 patients (21.3%) and 166 (13.7%) in the SIMA and BIMA grafting groups, respectively (hazard ratio, 0.78; 95% confidence interval, 0.66-0.92; P = 0.004). CONCLUSIONS: Bilateral internal mammary grafting is associated with lower long-term mortality than single internal mammary grafting. Moreover, this survival benefit comes at no increased perioperative morbidity or mortality cost.


Assuntos
Doença da Artéria Coronariana , Anastomose de Artéria Torácica Interna-Coronária , Idoso , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Anastomose de Artéria Torácica Interna-Coronária/efeitos adversos , Masculino , Artéria Torácica Interna/transplante , Pessoa de Meia-Idade , Morbidade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
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