Unusual CD4+CD28nullT Lymphocytes and Recurrence of Acute Coronary Events

ObjectivesWe hypothesized that the expansion of unusual T lymphocytes, CD4+CD28nullT cells, might represent a key pathogenetic mechanism of recurrent instability.BackgroundClinical presentation of acute coronary syndromes (ACS) is variable. Some patients have recurrent episodes of instability, despite optimal treatment, whereas others have a single acute event in their life. The CD4+CD28nullT cells, with a functional profile that favors vascular injury, have recently been found both in peripheral blood and in unstable coronary plaques of patients with ACS.MethodsPeripheral blood T cells from 120 consecutive unstable angina (UA) patients were analyzed for the distribution of T-cell subsets by flow cytometry. Patients were subgrouped according to the occurrence of prior (during the 24 months before the study enrollment) and subsequent (during the 24 months of follow-up) acute coronary events. For 51 patients, the index event was the first ever (G1); 30 patients had prior events (G2); and 39 patients had further events at follow-up (death, myocardial infarction, or UA) or both before and after the index event (G3).ResultsThe CD4+CD28nullT-cell frequency was higher in G3 than in G2 and G1 (median 9.5% [range 2.4% to 48.0%] vs. 5.1% [range 0.4% to 27.8%] and 2.3% [range 0.2% to 22.8%], respectively; p < 0.001). The expansion of these unusual T lymphocytes was higher in patients with elevated C-reactive protein levels, and it was reduced by statin therapy. On multivariate logistic regression analysis, CD4+CD28nullT-cell frequency was an independent predictor of future acute coronary events (odds ratio 3.01, 95% confidence interval 1.1 to 8.25; p = 0.023).ConclusionsA perturbation of T-cell repertoire is strongly associated with the recurrence of acute coronary events, conceivably playing a key pathogenetic role

Bringing Stellar Evolution & Feedback Together: Summary of proposals from the Lorentz Center Workshop, 2022

Stars strongly impact their environment, and shape structures on all scales throughout the universe, in a process known as ``feedback''. Due to the complexity of both stellar evolution and the physics of larger astrophysical structures, there remain many unanswered questions about how feedback operates, and what we can learn about stars by studying their imprint on the wider universe. In this white paper, we summarize discussions from the Lorentz Center meeting `Bringing Stellar Evolution and Feedback Together' in April 2022, and identify key areas where further dialogue can bring about radical changes in how we view the relationship between stars and the universe they live in.Comment: Accepted to the Publications of the Astronomical Society of the Pacifi

Paradoxical preservation of vascular function in severe obesity

BACKGROUND: Obesity is associated with a high risk of coronary artery disease morbidity and mortality. Yet, postmortem studies have shown that severely obese subjects exhibit smooth coronary arteries, thus suggesting that they may be protected from atherosclerosis. We assessed vascular function and its possible determinants in a cohort of normal-weight to severely obese insulin-sensitive subjects (body mass index [BMI] 23.2-49 kg/m(2)). METHODS: Seventy-one healthy, insulin-sensitive subjects (Homeostasis Model Assessment of Insulin Resistance index <2.5), divided into normal-weight (n = 13; BMI = 23.2 +/- 1.6), obese (n = 35; BMI=32.6+/-2.5), and severely obese (n=23; BMI=49.0+/-7.9) groups, were enrolled. Vascular function was evaluated by flow-mediated dilation and carotid intima-media thickness. High-sensitivity C-reactive protein, leptin, adiponectin, vascular growth factors, and CD34+KDR+/CD133+ endothelial progenitor cells, known markers of vascular health/protection, also were measured. RESULTS: Flow-mediated dilation was higher in severely obese than in obese and normal-weight individuals (P=.019 and P=.011 respectively). Intima-media thickness was consistently lower in severely obese than in obese individuals (P=.040) and similar in severely obese and normal-weight individuals (P >.99). Levels of high-sensitivity C-reactive protein and leptin were higher in severely obese than in obese and normal-weight individuals (high-sensitivity C-reactive protein: P=.018 and P=.05, respectively; leptin: P <.001 for both comparisons). CD34+KDR+ endothelial progenitor cells were significantly higher in severely obese versus obese individuals (P=.039). CONCLUSION: Our study demonstrates that vascular function is paradoxically better in severely obese than in obese subjects and similar to that found in normal-weight subjects. Despite higher levels of high-sensitivity C-reactive protein and leptin, severely obese individuals may be partially protected from atherosclerosis, possibly by a greater mobilization of endothelial progenitor cells

Bringing Stellar Evolution and Feedback Together:Summary of Proposals from the Lorentz Center Workshop

Stars strongly impact their environment, and shape structures on all scales throughout the universe, in a process known as “feedback.” Due to the complexity of both stellar evolution and the physics of larger astrophysical structures, there remain many unanswered questions about how feedback operates and what we can learn about stars by studying their imprint on the wider universe. In this white paper, we summarize discussions from the Lorentz Center meeting “Bringing Stellar Evolution and Feedback Together” in 2022 April and identify key areas where further dialog can bring about radical changes in how we view the relationship between stars and the universe they live in.</p

Bringing Stellar Evolution and Feedback Together: Summary of Proposals from the Lorentz Center Workshop

Stars strongly impact their environment, and shape structures on all scales throughout the universe, in a process known as "feedback." Due to the complexity of both stellar evolution and the physics of larger astrophysical structures, there remain many unanswered questions about how feedback operates and what we can learn about stars by studying their imprint on the wider universe. In this white paper, we summarize discussions from the Lorentz Center meeting "Bringing Stellar Evolution and Feedback Together" in 2022 April and identify key areas where further dialog can bring about radical changes in how we view the relationship between stars and the universe they live in