RESUMO
Clinical and epidemiological evidence has recently revealed a link between coronary artery disease (CAD) and cancer. Shared risk factors and common biological pathways are probably involved in both pathological conditions. The aim of this paper was to evaluate whether and which conventional risk factors and novel circulating biomarkers could predict cancer incidence and death in patients with CAD. The study included 750 CAD patients, who underwent blood sampling for the evaluation of systemic inflammatory indexes (NLR and SII) and specific biomarkers of oxidative damage (leukocyte telomere length (LTL), mitochondrial DNA copy number (mtDNAcn)). Study participants were followed up for a mean of 5.4 ± 1.2 years. Sixty-seven patients (8.9%) developed cancer during the follow-up time, and nineteen (2.5%) died of cancer. Cox multivariable analysis revealed that age (HR = 1.071; 95% CI: 1.034-1.109; p < 0.001), smoking habit (HR = 1.994; 95% CI: 1.140-3.488; p = 0.016), obesity (HR = 1.708; 95% CI: 1.022-2.854; p = 0.041) and SII (HR = 1.002; 95% CI: 1.001-1.003; p = 0.045) were associated with cancer incidence, while only age (HR = 1.132; 95% CI: 1.052-1.219; p = 0.001) was a predictor of cancer death. Patients with lung and gastrointestinal cancers had significantly higher median mtDNAcn levels than those without cancer. Our study suggests that aggressive risk factor modification and suppression of chronic inflammation may be essential to preventing cancer in CAD patients.
Assuntos
Doença da Artéria Coronariana , Neoplasias , Humanos , Doença da Artéria Coronariana/epidemiologia , Incidência , Leucócitos/patologia , Neoplasias/epidemiologia , Neoplasias/patologia , Fatores de Risco , Biomarcadores , DNA Mitocondrial/genéticaRESUMO
Circulating cell-free DNA (ccf-DNA) and mtDNA (ccf-mtDNA) have often been used as indicators of cell death and tissue damage in acute and chronic disorders, but little is known about changes in ccf-DNA and ccf-mtDNA concentrations following radiation exposure. The aim of the study was to investigate the impact of chronic low-dose radiation exposure on serum ccf-DNA levels and ccf-mtDNA fragments (mtDNA-79 and mtDNA-230) of interventional cardiologists working in high-volume cardiac catheterization laboratory to assess their possible role as useful radiation biomarkers. We enrolled 50 interventional cardiologists (26 males; age = 48.4 ± 10 years) and 50 age- and gender-matched unexposed controls (27 males; age = 47.6 ± 8.3 years). Quant-iT™ dsDNA High-Sensitivity assay was used to measure circulating ccf-DNA isolated from serum samples. Quantitative analysis of mtDNA fragments was performed by real-time PCR. No significant relationships were found between ccf-DNA and ccf-mtDNA, and age, gender, smoking, or other clinical parameters. Ccf-DNA levels (44.2 ± 31.1 vs. 30.6 ± 19.2 ng/ml, P = 0.013), ccf-mtDNA-79 (2.6 ± 2.1 vs. 1.1 ± 0.8, P < 0.01), and ccf-mtDNA-230 copies (2.0 ± 1.8 vs. 1.04 ± 0.9, P = 0.02) were significantly higher in interventional cardiologists compared with the non-exposed group. In a subset (n = 15) of interventional cardiologists with a reliable reconstruction of cumulative professional exposure (59.7 ± 48.4 mSv; range: 1.4-182 mS), ccf-DNA (53.2 ± 41.3 vs. 36.4 ± 22.9 and 32.2 ± 20.5, P = 0.08), mtDNA-79 (2.4 ± 2.1 vs. 2.03 ± 1.7 and 1.09 ± 0.82, P = 0.05), and mtDNA-230 (2.0 ± 2.2 vs. 1.5 ± 1.4 and 1.04 ± 0.9, P = 0.09) tended to be significantly increased in high-exposure subjects compared with both low-exposure interventional cardiologists and controls. Our results provide evidence for a possible role of circulating DNA as a relevant biomarker of cellular damage induced by exposure to chronic low-dose radiation.
Assuntos
DNA Mitocondrial/sangue , DNA/sangue , Exposição Ocupacional/análise , Adulto , Biomarcadores/sangue , Biomarcadores/metabolismo , Serviço Hospitalar de Cardiologia , DNA/genética , DNA Mitocondrial/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Médicos , Reação em Cadeia da Polimerase , Doses de Radiação , Radiação IonizanteRESUMO
Mitochondrial DNA (mtDNA) and telomere shortening have been proposed as important contributors to vascular disease and atherogenesis. The role of mitochondrial and telomere alterations has been examined frequently, but usually separately. Recently, an integrated model in which DNA damage and metabolic pathways intersect in age-associated cardiovascular disease has been proposed. In this study we developed a fast and reliable real-time PCR-based procedure to investigate relative quantification of the 4,977 bp mitochondrial DNA deletion (also indicated as "mtDNA(4977) deletion"), employing TaqMan probes with a multiplex approach. As a validation of the assay, a nested PCR coamplification was performed. Telomere shortening was evaluated by a real-time monochrome multiplex PCR technique employing a SybrGreen-based analysis. The study of mtDNA(4977) deletion and telomere shortening was carried out in atrial biopsies from 11 patients undergoing coronary artery (n = 5) and valve surgery (n = 6). The relative quantifications showed that the amount of mtDNA(4977) deletion was greater in tissue of patients with coronary artery disease (CAD) (P = 0.01) and that telomere length (expressed as telomere length relative to a single copy reference gene) was significantly shorter in tissue of CAD patients, compared to patients without CAD (P = 0.03). Moreover, most conventional risk factors were significantly more frequent in CAD patients, smoking and dyslipidemia having the strongest association with the degree of mtDNA(4977) deletion and a significant correlation with telomere attrition (P = 0.02 and P = 0.006, respectively). In conclusion, the present study suggests that mtDNA(4977) deletion and telomere shortening may represent additional and synergic major risk factors for the pathogenesis of CAD and its complications.
Assuntos
Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/genética , DNA Mitocondrial/genética , Testes Genéticos/métodos , Reação em Cadeia da Polimerase Multiplex , Reação em Cadeia da Polimerase em Tempo Real , Deleção de Sequência/genética , Encurtamento do Telômero/genética , Idoso , Sequência de Bases , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Fatores de RiscoRESUMO
Biobanks are a critical resource for "omics" technologies in order to dissect molecular mechanism and gene-environmental interactions of common diseases, such as cancer, cardiovascular diseases, diabetes, and neurodegenerative diseases. Progress in basic biomedicine may contribute to advance personalised medicine in which treatments will no longer be "one size fits all", but instead "tailored" to the molecular and genetic profile of each patient. Currently, there are major efforts worldwide to professionalize biobanks in order to move ahead from a "do-it-yourself" tissue collection - as is most frequent at present - for providing high quality preservation and storage of biological samples with potentially greater scientific impact. In this paper, we describe our recent experience in the design and development of a high-security liquid nitrogen storage system (-196°C) as a key resource for biomedical research.
Assuntos
Bancos de Espécimes Biológicos/organização & administração , Pesquisa Biomédica/organização & administração , Nitrogênio , Plasma , Soro , Bancos de Espécimes Biológicos/ética , Pesquisa Biomédica/ética , Sangue , Humanos , Itália , Metabolômica , Proteômica , Manejo de Espécimes/normas , TranscriptomaRESUMO
Little information is available on peripheral levels of Hsp72, Hsp60, and anti-Hsp60 antibodies in patients with left ventricular (LV) dysfunction due to non-atherosclerotic cardiac disease. In this study, serum Hsp72, Hsp60 and anti-Hsp60 antibodies, IL-6, and C-reactive protein (CRP) were measured in 44 healthy controls and in 82 patients with angiographically normal coronary arteries (LV ejection fraction [EF] > or = 50%, n=22; -35% to <50%, n=32; <35%, n=28). Patients with more severe disease (more depressed myocardial blood flow at rest and during dipyridamole, indicative of coronary microvascular impairment) showed more elevated circulating Hsp60 and auto-antibodies, Hsp72, and CRP levels. IL-6 was increased progressively as a function of severity of LV dysfunction. Anti-Hsp60 antibodies, Hsp72, and IL-6 were significantly correlated with brain natriuretic peptide (BNP) levels and LV end-diastolic dimensions (LVEDD) values. IL-6 tended to be related with Hsp72 in particular in patients with more severe disease (r = 0.45, P = 0.021). Hsp60 and Hsp72 activation and inflammatory markers were correlated with the extent of cardiac and microvascular dysfunction in patients with angiographycally normal coronary arteries. These results suggest a pathogenic role of infective-metabolic insult and inflammatory reaction in the development of vascular and myocardial damage in patients with heart failure even in the absence of overt coronary artery disease.