Anxiety and its associated disorders are common in patients with cardiovascular disease and may significantly influence cardiac health. Anxiety disorders are associated with the onset and progression of cardiac disease, and in many instances have been linked to adverse cardiovascular outcomes, including mortality. Both physiologic (autonomic dysfunction, inflammation, endothelial dysfunction, changes in platelet aggregation) and health behavior mechanisms may help to explain the relationships between anxiety disorders and cardiovascular disease. Given the associations between anxiety disorders and poor cardiac health, the timely and accurate identification and treatment of these conditions is of the utmost importance. Fortunately, pharmacologic and psychotherapeutic interventions for the management of anxiety disorders are generally safe and effective. Further study is needed to determine whether interventions to treat anxiety disorders ultimately impact both psychiatric and cardiovascular health.

Rationale B cells are abundant in the adventitia of normal and diseased vessels. Yet, the molecular and cellular mechanisms mediating homing of B cells to the vessel wall and B cell effects on atherosclerosis are poorly understood. Inhibitor of Differentiation-3 (Id3), is important for atheroprotection in mice and polymorphism in the human ID3 gene has been implicated as a potential risk marker of atherosclerosis in humans. Yet the role of Id3 in B cell regulation of atherosclerosis is unknown. Objective To determine if Id3 regulates B cell homing to the aorta and atheroprotection, and identify molecular and cellular mechanisms mediating this effect. Methods and Results Loss of Id3 in Apoe−/− mice resulted in early and increased atherosclerosis. Flow cytometry revealed a defect in Id3−/− Apoe−/− mice in the number of B cells in the aorta, but not the spleen, lymph nodes and circulation. Similarly, B cells transferred from Id3−/− Apoe−/− mice into B cell deficient micereconstituted spleen, lymph node and blood similarly to B cells from Id3+/+ Apoe−/− mice, but aortic reconstitution and B cell-mediated inhibition of diet-induced atherosclerosis was significantly impaired. In addition to retarding initiation of atherosclerosis, B cells homed to regions of existing atherosclerosis, reduced macrophage content in plaque and attenuated progression of disease. The chemokine receptor, CCR6, was identified as an important Id3 target mediating aortic homing and atheroprotection. Conclusions Together, these results are the first to identify the Id3-CCR6 pathway in B cells and demonstrate its role in aortic B cell homing and B cell mediated protection from early atherosclerosis.

Though much of the research on atherosclerosis has focused on the intimal accumulation of lipids and inflammatory cells, there is an increasing amount of interest in the role of the adventitia in coordinating the immune response in atherosclerosis. In this review of the contributions of the adventitia and adventitial lymphocytes to the development of atherosclerosis, we discuss recent research on the formation and structural nature of adventitial immune aggregates, potential mechanisms of crosstalk between the intima, media, and adventitia, specific contributions of B lymphocytes and T lymphocytes, and the role of the vasa vasorum and surrounding perivascular adipose tissue (PVAT). Furthermore, we highlight techniques for the imaging of lymphocytes in the vasculature.

Clinicaltrials.gov, NCT02754895.