Reactive Oxidative Species-Modulated Ca2+ Release Regulates ß2 Integrin Activation on CD4+ CD28null T Cells of Acute Coronary Syndrome Patients.

The number and activity of T cell subsets in the atherosclerotic plaques are critical for the prognosis of patients with acute coronary syndrome. ß2 Integrin activation is pivotal for T cell recruitment and correlates with future cardiac events. Despite this knowledge, differential regulation of adhesiveness in T cell subsets has not been explored yet. In this study, we show that in human T cells, SDF-1α-mediated ß2 integrin activation is driven by a, so far, not-described reactive oxidative species (ROS)-regulated calcium influx. Furthermore, we show that CD4+CD28null T cells represent a highly reactive subset showing 25-fold stronger ß2 integrin activation upon SDF-1α stimulation compared with CD28+ T cells. Interestingly, ROS-dependent Ca release was much more prevalent in the pathogenetically pivotal CD28null subset compared with the CD28+ T cells, whereas the established mediators of the classical pathways for ß2 integrin activation (PKC, PI3K, and PLC) were similarly activated in both T cell subsets. Thus, interference with the calcium flux attenuates spontaneous adhesion of CD28null T cells from acute coronary syndrome patients, and calcium ionophores abolished the observed differences in the adhesion properties between CD28+ and CD28null T cells. Likewise, the adhesion of these T cell subsets was indistinguishable in the presence of exogenous ROS/H2O2 Together, these data provide a molecular explanation of the role of ROS in pathogenesis of plaque destabilization.

Association of respiratory infections and the impact of vaccinations on cardiovascular diseases.

Influenza, pneumococcal, severe acute respiratory syndrome coronavirus 2, and respiratory syncytial virus infections are important causes of high morbidity and mortality in the elderly. Beyond the burden of infectious diseases, they are also associated with several non-infectious complications like cardiovascular events. A growing body of evidence in prospective studies and meta-analyses has shown the impact of influenza and pneumococcal vaccines on types of cardiovascular outcomes in the general population. Influenza vaccination showed a potential benefit for primary and secondary prevention of cardiovascular diseases across all ages. A reduced risk of cardiovascular events for individuals aged 65 years and older was associated with pneumococcal vaccination. Despite scientific evidence on the effectiveness, safety, and benefits of the vaccines and recommendations to vaccinate elderly patients and those with risk factors, vaccination rates remain sub-optimal in this population. Doubts about vaccine necessity or efficacy and concerns about possible adverse events in patients and physicians refer to delayed acceptance. Vaccination campaigns targeting increasing professional recommendations and public perceptions should be implemented in the coming years. The aim of this review paper is to summarize the effect of vaccination in the field of cardiovascular disease to achieve a higher vaccination rate in this patient population.