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1.
Cell ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38971151

RESUMO

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841). Neoadjuvant monotherapy with the PARP inhibitor (PARPi) niraparib achieves impressive 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively. We identify effector regulatory T cells (eTregs) as key responders to HRD and neoadjuvant therapies, co-occurring with other tumor-reactive T cells, particularly terminally exhausted CD8+ T cells (Tex). TME-wide interferon signaling correlates with cancer cells upregulating MHC class II and co-inhibitory ligands, potentially driving Treg and Tex fates. Depleting eTregs in HRD mouse models, with or without PARP inhibition, significantly suppresses tumor growth without observable toxicities, underscoring the potential of eTreg-focused therapeutics for HGSOC and other HRD-related tumors.

2.
J Thorac Dis ; 16(4): 2341-2352, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38738257

RESUMO

Background: Intracardiac echocardiography (ICE) is a novel technology with certain advantages in treatment of atrial fibrillation (AF), yet there is limited research on the use of ICE in radiofrequency ablation for AF treatment in China. The aim of this study was to investigate the total fluoroscopy time and dose, safety, and effectiveness of ICE guided vs. traditional fluoroscopy (non-ICE) guided radiofrequency ablation for AF in China. Methods: We conducted a single-center retrospective analysis of patients who underwent ICE or traditional fluoroscopy-guided radiofrequency ablation for AF. The primary endpoint of this study was total fluoroscopy time, and the secondary endpoints included total fluoroscopy dose, acute surgery failure, transseptal puncture time, ablation time, total procedure time, and 6-month surgery success (no AF recurrence or atrial flutter). As an exploratory analysis, outcomes of interest by different types of AF were examined. Results: A total of 97 patients were included in the analysis. Forty-eight were in the ICE group and 49 were in the non-ICE group with comparable demographic and clinical characteristics at the baseline. None of patients experienced acute surgery failure with no major procedure-related complications occurred. The fluoroscopic time and dose were significantly lower in the ICE group compared to the non-ICE group (0.00 vs. 9.67±4.88 min, P<0.001; 0.00 vs. 77.10±44.28 mGy/cm2, P<0.001, respectively). There were no statistically significant differences in transseptal puncture time, ablation time and total procedure time between the two groups. There were two AF recurrences observed during the 6-month follow-up in each group (P>0.99). Conclusions: ICE significantly reduced the fluoroscopic time and dose for radiofrequency catheter ablation in AF patients. There were no significant differences in safety or effectiveness outcomes between the ICE and non-ICE groups.

3.
Mol Cancer Ther ; 22(4): 447-458, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-36780236

RESUMO

Therapy-induced senescence (TIS) is common in tumor cells treated with PARP inhibitors (PARPis) and can serve as a promising target for improving PARPi efficacy. However, whether stromal components within the tumor microenvironment undergo TIS caused by PARPis and contribute to consequential treatment failure remain unclear. We previously revealed that PARPis triggered a senescence-like secretory phenotype in stromal fibroblasts. Here, we further explored PARPi-induced senescence in the stroma, its contribution to PARPi resistance, and opportunities to leverage stromal TIS for improved PARPi sensitivity. In this study, we demonstrated that tumor tissues from patients treated with neoadjuvant PARPis showed a significant senescence-like phenotype in the stroma. Moreover, PARPi-induced senescent cancer-associated fibroblasts (CAFs) displayed a senescence-associated secretory phenotype (SASP) profile that was sufficient to induce tumor resistance to PARPis in both homologous recombination-deficient (HRD) and -proficient ovarian cancer cells. Using the GLAD4U database, we found that bepotastine, an approved H1-antihistamine, inhibited the SASP of PARPi-primed CAFs at clinical serum concentrations. We further demonstrated that bepotastine attenuated fibroblast-facilitated tumor resistance to PARPis in three-dimensional organotypic cultures and HRD-positive patient-derived xenograft models. Mechanistically, bepotastine suppressed PARPi-triggered SASP by inhibiting NF-κB signaling independent of the histamine H1 receptor. Taken together, our results highlight the importance of stromal TIS and SASP in PARPi resistance, and targeting SASP with bepotastine may be a promising therapeutic option for improving PARPi sensitivity in ovarian cancer.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Ovarianas , Feminino , Humanos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , NF-kappa B , Fibroblastos Associados a Câncer/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Fibroblastos , Senescência Celular , Microambiente Tumoral
4.
Front Oncol ; 12: 820696, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35756622

RESUMO

Background: Immunotherapy is the most promising treatment in triple-negative breast cancer (TNBC), and its efficiency is largely dependent on the intra-tumoral immune cells infiltrations. Thus, novel ways to assist immunotherapy by increasing immune cell infiltrations were highly desirable. Methods: To find key immune-related genes and discover novel immune-evoking molecules, gene expression profiles of TNBC were downloaded from Gene Expression Omnibus (GEO). Single-sample gene set enrichment analysis (ssGSEA) and Weighted Gene Co-expression Network Analysis (WGCNA) were conducted to identified hub genes. The CMap database was used subsequently to predicate potential drugs that can modulate the overall hub gene expression network. In vitro experiments were conducted to assess the anti-tumor activity and the pyroptosis phenotypes induced by GW-8510. Results: Gene expression profiles of 198 TNBC patients were downloaded from GEO dataset GSE76124, and ssGSEA was used to divide them into Immune Cell Proficiency (ICP) group and Immune Cell Deficiency (ICD) group. Hub differential expressed gene modules between two groups were identified by WGCNA and then annotated by Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. A cyclin-dependent kinase (CDK) 2 inhibitor, GW-8510 was then identified by the CMap database and further investigated. Treatment with GW-8510 resulted in potent inhibition of TNBC cell lines. More importantly, in vitro and in vivo studies confirmed that GW-8510 and other CDK inhibitors (Dinaciclib, and Palbociclib) can induce pyroptosis by activating caspase-3 and GSDME, which might be the mechanism for their immune regulation potentials. Conclusion: GW-8510, as well as other CDK inhibitors, might serve as potential immune regulators and pyroptosis promotors in TNBC.

5.
Front Oncol ; 12: 852772, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402241

RESUMO

Background: Ovarian cancer (OC) is a heterogeneous gynecological malignancy with a poor prognosis as the majority of patients are diagnosed at an advanced stage. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is recommended for patients who cannot achieve optimal cytoreduction or cannot endure primary debulking surgery (PDS). As there is an increased risk of chemoresistance for platinum-based NACT, it is important to investigate an alternative option. A Poly (ADP-ribose) polymerase inhibitor (PARPi), niraparib, has shown high anti-tumor activity, especially in homologous recombination deficiency (HRD) positive patients with OC. Thus, niraparib as a neoadjuvant treatment agent may help improve surgery accessibility and create survival benefits. Methods: This multicenter, prospective, single-arm, open-label, phase II study plans to recruit 53 patients (aged 18-75 years) with newly diagnosed HRD positive, unresectable (Fagotti score ≥ 8 or upper abdominal computed tomography [CT] score ≥ 3) International Federation of Gynecology and Obstetrics (FIGO) stage III-IV OC. The HRD status was detected by next-generation sequencing and HRD positive patients will be counseled for study participation. Enrolled patients will receive niraparib capsules QD (200mg or 300mg per day) for two cycles (4 weeks/cycle). After neoadjuvant niraparib treatment, patients exhibiting complete response (CR), partial response (PR), or stable disease (SD) will undergo tumor reduction surgery and subsequent standard carboplatin/paclitaxel-based chemotherapy. The primary objectives include the objective response rate (ORR) and R0 resection rate. The rate of treatment interruption/termination and progression-free survival (PFS) will be secondary objectives. The study uses Simon's optimal two-stage design (24 and 21 patients for the first and second stage respectively). The data manager will record all adverse events (AEs). Discussion: This is the first prospective study to evaluate the effectiveness and safety of niraparib in neoadjuvant treatment for advanced OC. The result of this study will provide a solid base for further expanding the clinical applications of the PAPRi and exploring more therapeutic possibilities for patients with HRD positive advanced OC. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT04507841.

6.
J Exp Clin Cancer Res ; 40(1): 292, 2021 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-34538264

RESUMO

BACKGROUND: Ovarian cancer (OC) progression is an unmet medical challenge. Since omental metastases were palpated harder than their primary counterparts during cytoreductive surgery of patients with epithelial ovarian cancer (EOC), we were inspired to investigate OC progression from the perspective of biomechanics. METHODS: Atomic Force Microscope (AFM) was used to measure the Young's modulus of tissues. The collagen-coated polyacrylamide hydrogel (PA gel) system was prepared to mimic the soft and stiff substrates in vitro. The effect of TAGLN was evaluated both in vitro and in vivo using transwell assay, immunofluorescence, western blot analysis and immunohistochemistry. RESULTS: We quantitatively confirmed that omental metastases were stiffer and more abundant in desmoplasia compared with paired primary tumors, and further demonstrated that matrix stiffness could notably regulate OC progression. Remarkably, TAGLN, encoding an actin cross-linking/gelling protein, was identified as a potent mechanosensitive gene that could form a regulation loop with Src activation reacting to environmental stiffness, thus mediating stiffness-regulated OC progression through regulating RhoA/ROCK pathway. CONCLUSIONS: These data demonstrate that targeting extra-cellular matrix (ECM) stiffness could probably hamper OC progression, and of note, targeting TAGLN might provide promising clinical therapeutic value for OC therapy.


Assuntos
Proteínas dos Microfilamentos/metabolismo , Proteínas Musculares/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Transdução de Sinais , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Progressão da Doença , Matriz Extracelular/metabolismo , Feminino , Imunofluorescência , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Camundongos , Proteínas dos Microfilamentos/genética , Modelos Biológicos , Proteínas Musculares/genética , Metástase Neoplásica , Neoplasias Ovarianas/etiologia , Neoplasias Ovarianas/mortalidade , Prognóstico , Microambiente Tumoral , Quinases da Família src/genética , Quinases da Família src/metabolismo
7.
NPJ Precis Oncol ; 5(1): 49, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108603

RESUMO

Cancer-associated fibroblasts (CAFs) play significant roles in drug resistance through different ways. Antitumor therapies, including molecular targeted interventions, not only effect tumor cells but also modulate the phenotype and characteristics of CAFs, which can in turn blunt the therapeutic response. Little is known about how stromal fibroblasts respond to poly (ADP-ribose) polymerase inhibitors (PARPis) in ovarian cancer (OC) and subsequent effects on tumor cells. This is a study to evaluate how CAFs react to PARPis and their potential influence on PARPi resistance in OC. We discovered that OC stromal fibroblasts exhibited intrinsic resistance to PARPis and were further activated after the administration of PARPis. PARPi-challenged fibroblasts displayed a specific secretory profile characterized by increased secretion of CCL5, MIP-3α, MCP3, CCL11, and ENA-78. Mechanistically, increased secretion of CCL5 through activation of the NF-κB signaling pathway was required for PARPi-induced stromal fibroblast activation in an autocrine manner. Moreover, neutralizing CCL5 partly reversed PARPi-induced fibroblast activation and boosted the tumor inhibitory effect of PARPis in both BRCA1/2-mutant and BRCA1/2-wild type xenograft models. Our study revealed that PARPis could maintain and improve stromal fibroblast activation involving CCL5 autocrine upregulation. Targeting CCL5 might offer a new treatment modality in overcoming the reality of PARPi resistance in OC.

8.
Circ Arrhythm Electrophysiol ; 13(9): e008446, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32718185

RESUMO

BACKGROUND: Peri-mitral atrial flutters frequently develop post-atrial fibrillation ablation or postcardiac surgery. The determinants of the flutter wave morphology on surface ECG have been less studied. METHODS: We retrospectively reviewed 24 patients with peri-mitral atrial flutters who underwent biatrial high-resolution mapping at 3 institutions with LUMIPOINT software. We analyzed the overlap between the right atrial (RA) activation time and flutter wave duration and compared the proportion of the endocardial area that was activated in both atria during the flutter wave duration. Biatrial activation patterns and interatrial conductions were also identified. RESULTS: The mean tachycardia cycle length was 264±60 ms, with RA activation time 155±45 ms (60.8±20.6% of the tachycardia cycle length), and the flutter wave duration 107±31 ms (41.6±11.7% of the tachycardia cycle length). The overlap between the RA activation time and the flutter wave duration was 102±29 ms, which takes 68.5±17.2% of the RA activation time and 95.7±9.1% of the flutter wave duration, respectively. Quantitative analysis also showed that during the flutter wave duration, more percentage of the endocardial area was activated in the RA than in the left atrium (73.0±12.7% versus 45.2±13.0%, P<0.001). We consistently observed that the RA anterior wall rightward activation corresponded to the positive component in V1 in both flutter patterns, and the RA downward activation corresponded to the positive component in the counterclockwise group or the upward activation corresponded to the negative component in the clockwise group in the inferior leads. The passive RA activation patterns were varied with spontaneous atrial scarring or previous linear ablation. CONCLUSIONS: ECG flutter wave morphology of peri-mitral atrial flutters is mainly dependent on RA activation patterns.


Assuntos
Potenciais de Ação , Flutter Atrial/diagnóstico , Função do Átrio Direito , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Átrios do Coração/fisiopatologia , Frequência Cardíaca , Idoso , Flutter Atrial/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Tempo
9.
J Cardiovasc Med (Hagerstown) ; 21(3): 200-208, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31977539

RESUMO

AIMS: Atrial fibrillation is the most common sustained arrhythmia in the general population, and circumferential pulmonary vein isolation has emerged as a cornerstone in the treatment of drug-resistant atrial fibrillation. However, there is a paucity of data regarding the CHA2DS2-VASc and SAMe-TT2R2 scores as predictors of outcomes among patients with nonvalvular atrial fibrillation on vitamin K antagonists after radiofrequency catheter ablation (RFCA). METHODS: The current prospective observational study enrolled 304 consecutive patients with atrial fibrillation who underwent RFCA. Warfarin was maintained for at least 3 months after RFCA. The 1-year atrial fibrillation recurrence rate was documented. RESULTS: Persistent atrial fibrillation (P = 0.003), heart failure (P < 0.001), an enlarged left atrium (P = 0.003), current smoking (P < 0.001), the CHA2DS2-VASc score (P = 0.001), and the SAMe-TT2R2 score (P < 0.001) were univariate associated with recurrent atrial fibrillation. Cutoff analysis showed that a CHA2DS2-VASc score at least 3 (areas under the curve = 0.612; 95% confidence interval 0.537-0.687) and a SAMe-TT2R2 score at least 5 (areas under the curve = 0.642, 95% confidence interval 0.575-0.708) had the highest predictive value for atrial fibrillation recurrence. Patients with a CHA2DS2-VASc score at least 3 (P < 0.001) and a SAMe-TT2R2 score at least 5 (P = 0.001) had a higher probability of experiencing atrial fibrillation recurrence after RFCA compared with patients with a CHA2DS2-VASc score less than 3 and a SAMe-TT2R2 score less than 5. CONCLUSION: CHA2DS2-VASc and SAMe-TT2R2 scores were associated with 1-year recurrence of atrial fibrillation in patients on vitamin K antagonists after RFCA. For CHA2DS2-VASc and SAMe-TT2R2 scores, a cutoff value of at least 3 and at least 5 had the highest predictive value for atrial fibrillation recurrence, respectively.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Técnicas de Apoio para a Decisão , Veias Pulmonares/cirurgia , Acidente Vascular Cerebral/prevenção & controle , Vitamina K/antagonistas & inibidores , Varfarina/administração & dosagem , Idoso , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Veias Pulmonares/fisiopatologia , Recidiva , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do Tratamento , Varfarina/efeitos adversos
10.
Basic Res Cardiol ; 111(6): 63, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27660282

RESUMO

Increased macrophage accumulation occurs in the atria of patients with atrial fibrillation (AF). However, the phenotype and functions of the macrophages in AF remain unclear. We investigated the macrophage-atrial myocyte interaction in AF patients and found that the increased macrophages were mainly pro-inflammatory macrophages (iNOS+, Arg1-). Tachypacing of HL-1 atrial myocytes also led to pro-inflammatory macrophage polarization. In addition, lipopolysaccharide (LPS)-stimulated pro-inflammatory macrophages-induced atrial electrical remodeling, evidenced by increased AF incidence and decreased atrial effective refractory period and L-type calcium currents (I Ca-L) in both canine and mouse AF models. Depletion of macrophages relieved LPS-induced atrial electrical remodeling, confirming the role of pro-inflammatory macrophages in the pathogenesis of AF. We also found that the effect of LPS-stimulated macrophages on atrial myocytes was mediated by secretion of interleukin 1 beta (IL-1ß), which inhibited atrial myocyte quaking protein (QKI) expression. IL-1ß knockout in macrophages restored the LPS-stimulated macrophage-induced inhibition of QKI and CACNA1C (α1C subunit of L-type calcium channel) in atrial myocytes. Meanwhile, QKI overexpression in atrial myocytes restored the LPS-stimulated macrophage-induced electrical remodeling through enhanced binding of QKI to CACNA1C mRNA, which upregulated the expression of CACNA1C as well as I Ca-L. In contrast, QKI knockout inhibited CACNA1C expression. Finally, using transcription factor activation profiling plate array and chromatin immunoprecipitation, we revealed that special AT-rich sequence binding protein 1 activated QKI transcription. Taken together, our study uncovered the functional interaction between macrophages and atrial myocytes in AF. AF induced pro-inflammatory macrophage polarization while pro-inflammatory macrophages exacerbated atrial electrical remodeling by secreting IL-1ß, further inhibiting QKI expression in atrial myocytes, which contributed to I Ca-L downregulation. Our study demonstrates a novel molecular mechanism underlying the pathogenesis and progression of AF and suggests that QKI is a potential therapeutic target.


Assuntos
Fibrilação Atrial/fisiopatologia , Comunicação Celular/fisiologia , Macrófagos/metabolismo , Miócitos Cardíacos/metabolismo , Adulto , Idoso , Animais , Fibrilação Atrial/metabolismo , Remodelamento Atrial/fisiologia , Western Blotting , Imunoprecipitação da Cromatina , Cães , Feminino , Átrios do Coração/metabolismo , Humanos , Ativação de Macrófagos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Técnicas de Patch-Clamp , Proteínas de Ligação a RNA/metabolismo , Ratos , Reação em Cadeia da Polimerase em Tempo Real
11.
Acta Biochim Biophys Sin (Shanghai) ; 47(3): 174-82, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25630653

RESUMO

Coronary artery disease (CAD) is a major health problem worldwide. The most severe form of CAD is acute coronary syndrome (ACS). Recent studies have demonstrated the beneficial role of atorvastatin in ACS; however, the mechanisms underlying this effect have not been fully clarified. Growing evidence indicates that activation of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) plays an important role in oxidative stress-induced cardiomyocyte apoptosis during ACS. In this study, we examined whether atorvastatin inhibits H2O2-induced LOX-1 expression and H9c2 cardiomyocyte apoptosis, and investigated the underlying signaling pathway. Treatment of H9c2 cardiomyocytes with H2O2 resulted in elevated expression of LOX-1 mRNA and protein, as well as increased caspase-3 and -9 protein expression and cell apoptosis. H2O2-induced LOX-1 expression, caspase protein expression, and cardiomyocyte apoptosis were attenuated by pretreatment with atorvastatin. Atorvastatin activated H2O2-inhibited phosphorylation of Akt in a concentration-dependent manner. The Akt inhibitor, LY294002, inhibited the effect of atorvastatin on inducing Akt phosphorylation and on suppressing H2O2-mediated caspase up-regulation and cell apoptosis. These findings indicate that atorvastatin protects cardiomyocyte from oxidative stress via inhibition of LOX-1 expression and apoptosis, and that activation of H2O2-inhibited phosphorylation of Akt may play an important role in the protective function of atorvastatin.


Assuntos
Atorvastatina/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cromonas/farmacologia , Peróxido de Hidrogênio/toxicidade , Morfolinas/farmacologia , Miócitos Cardíacos/citologia , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Receptores Depuradores Classe E/antagonistas & inibidores , Receptores Depuradores Classe E/genética , Receptores Depuradores Classe E/metabolismo , Transdução de Sinais/efeitos dos fármacos
12.
Clin Cardiol ; 32(1): 43-6, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19143004

RESUMO

BACKGROUND: Sex hormones play an important role in the development of cardiovascular disease. Testosterone and estradiol have been reported to be down-regulated in subjects with coronary artery disease and heart failure, but has not been studied in atrial fibrillation (AF). HYPOTHESIS: Levels of sex hormones may be associated with susceptibility to lone AF in men. METHODS: Fifty-eight male subjects who had electrocardiographic evidence of paroxysmal or chronic AF and a structurally normal heart on echocardiography were enrolled. Subjects were excluded if they had been taking angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), or statins within 3 mo or had a history of coronary artery disease, rheumatic heart disease, cardiomyopathy, significant valvular disease, hyperthyroidism, or hypertension. Fifty-eight controls were recruited from a healthy outpatient population. Serum total testosterone and estradiol levels were determined using a commercially available radioimmunoassay. RESULTS: Mean levels of testosterone were significantly lower in subjects with lone AF when compared with controls (476 ng/dl versus 514 ng/dl, p = 0.005). No significant differences were found in the estradiol levels between the 2 groups (31.9 pg/ml versus 32.4 pg/ml, p = 0.789). CONCLUSION: Reduced testosterone levels may be associated with susceptibility to lone AF in men.


Assuntos
Fibrilação Atrial/sangue , Testosterona/sangue , Suscetibilidade a Doenças/sangue , Eletrocardiografia , Estradiol/sangue , Humanos , Masculino , Pessoa de Meia-Idade
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