REGINA MARIA DE CARVALHO PINTO
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/09 - Laboratório de Pneumologia, Hospital das Clínicas, Faculdade de Medicina
LIM/09 - Laboratório de Pneumologia, Hospital das Clínicas, Faculdade de Medicina
3 resultados
Resultados de Busca
Agora exibindo 1 - 3 de 3
- Age-associated phenotypic imbalance in TCD4 and TCD8 cell subsets: comparison between healthy aged, smokers, COPD patients and young adults(2022) FERNANDES, Juliana Ruiz; PINTO, Thalyta Nery Carvalho; ARRUDA, Lia Barbara; SILVA, Cibele Cristine Berto Marques da; CARVALHO, Celso Ricardo Fernandes de; PINTO, Regina Maria Carvalho; DUARTE, Alberto Jose da Silva; BENARD, GilBackground COPD is associated with an abnormal lung immune response that leads to tissue damage and remodeling of the lung, but also to systemic effects that compromise immune responses. Cigarette smoking also impacts on innate and adaptative immune responses, exerting dual, pro- and anti-inflammatory effects. Previously, we showed that COPD patients presented accelerated telomere shortening and decreased telomerase activity, while, paradoxically, cigarette-smokers exhibited preserved telomerase activity and slower rate of telomere shortening. Results Here, we evaluated the naive, CM, EM and T-EMRA subsets of TCD4 and TCD8 cells according to the expression of CCR7/CD45RA. We compared age-matched COPD patients, cigarette-smokers without clinical-laboratory evidence of pulmonary compromise, and healthy individuals. They were additionally compared with a group of young adults. For each subset we analysed the expression of markers associated with late differentiation, senescence and exhaustion (CD27/CD28/CD57/KLRG1/PD1). We show that COPD patients presented a drastically reduced naive cells pool, and, paradoxically, increased fractions of naive cells expressing late differentiation, senescence or exhaustion markers, likely impacting on their immunocompetence. Pronounced phenotypic alterations were also evidenced in their three memory T-cell subsets compared with the other aged and young groups, suggesting an also dysfunctional memory pool. Surprisingly, our smokers showed a profile closer to the Healthy aged than COPD patients. They exhibited the usual age-associated shift of naive to EM TCD4 and TCD8 cells, but not to CM or T-EMRA T-cells. Nonetheless, their naive T-cells phenotypes were in general similar to those of the Youngs and Healthy aged, suggesting a rather phenotypically preserved subset, while the memory T-cells exhibited increased proportions of cells with the late-differentiation or senescence/exhaustion markers as in the Healthy aged. Conclusion Our study extends previous findings by showing that COPD patients have cells expressing a full range of late differentiated, senescent or exhausted phenotypes encompassing all TCD4 and TCD8 subsets, consistent with a premature immunosenescence phenotype. Surprisingly, the smokers group's results suggest that moderate to heavy chronic cigarette smoking did not accelerate the pace of immunosenescence as compared with the Healthy aged.
- Integrative assessment of cerebral blood regulation in COPD patients(2024) CORRE, Daniel I.; DE-LIMA-OLIVEIRA, Marcelo; NOGUEIRA, Ricardo C.; CARVALHO-PINTO, Regina M.; BOR-SENG-SHU, Edson; PANERAI, Ronney B.; CARVALHO, Celso R. F.; SALINET, Angela S. M.Cerebrovascular responses were compared between COPD and non-COPD participants. The association between COPD severity and cognitive function was also investigated. Cerebral blood velocity in the middle cerebral artery, blood pressure, and end-tidal CO2 were recorded at rest, followed by a brain activation paradigm, and an inhaled gas mixture (5% CO2) to assess cerebral autoregulation (CA), neurovascular coupling (NVC) and cerebrovascular reactivity to carbon dioxide (CVRCO2), respectively. Pulmonary function, blood gas analysis (COPD) and cognitive function (MoCA test) were also performed. No difference in baseline (systemic and cerebral parameters) and CA was found between 20 severe COPD and 21 non-COPD. Reduced NVC and CVRCO2 test were found in the COPD group. Lower pulmonary function was positively correlated with CA, NVC and CVRCO2 in COPD patients. Cognitive impairment (MoCA<26) was associated with lower NVC responses (COPD and non-COPD) and lower pulmonary function (COPD). Both mechanisms, CVRCO2 and NVC, were lower in COPD patients. Moreover, disease severity and cognitive impaired were associated with worse cerebrovascular regulation.
- Long-term tobacco exposure and immunosenescence: Paradoxical effects on T-cells telomere length and telomerase activity(2021) FERNANDES, Juliana Ruiz; PINTO, Thalyta Nery Carvalho; PIEMONTE, Lucas Lopes; ARRUDA, Lia Barbara; SILVA, Cibele Cristine Berto Marques da; CARVALHO, Celso R. F.; PINTO, Regina Maria Carvalho; DUARTE, Alberto J. S.; BENARD, GilImmunosenescence are alterations on immune system that occurs throughout an individual life. The main characteristic of this process is replicative senescence, evaluated by telomere shortening. Several factors implicate on telomere shortening, such as smoking. In this study, we evaluated the influence of smoking and Chronic Obstructive Pulmonary Disease (COPD) on cytokines, telomere length and telomerase activity. Blood samples were collected from subjects aged over 60 years old: Healthy (never smokers), Smokers (smoking for over 30 years) and COPDs (ex-smokers for >= 15 years). A young group was included as control. PBMCs were cultured for assessment of telomerase activity using RT-PCR, and cytokines secretion flow cytometry. CD4+ and CD8+ purified lymphocytes were used to assess telomere length using FlowFISH. We observed that COPD patients have accelerated telomere shortening. Paradoxically, smokers without lung damage showed preserved telomere length, suggesting that tobacco smoking may affect regulatory mechanisms, such as telomerase. Telomerase activity showed diminished activity in COPDs, while Smokers showed increased activity compared to COPDs and Healthy groups. Extracellular environment reflected this unbalance, indicated by an anti-inflammatory profile in Smokers, while COPDs showed an inflammatory prone profile. Further studies focusing on telomeric maintenance may unveil mechanisms that are associated with cancer under long-term smoking.