Local and Systemic Cellular Immunity in Early Renal Artery Atherosclerosis

Abstract

SummaryBackground and objectives Modern imaging techniques have increased the incidental detection of renal atherosclerotic disease (RAD). Because immune activation may hasten RAD progression, identifying cellular immune markers might provide clues to clinical activity. In this study, cellular immune markers were assessed in early RAD.Design, setting, participants, & measurements Immune cell markers in peripheral blood of two groups of hypertensive patients with normal carotid and coronary arteries were evaluated: 28 patients had incidental RAD and 22 patients had normal renal arteries; 21 renal arteries obtained at necropsy from individuals with history of hypertension and tissue evidence of RAD were examined and matched with 21 individuals with normal renal arteries. Cell subpopulations were measured by flow cytometry in peripheral blood and direct cell count, respectively, using T and dendritic cells monoclonal antibodies.Results Peripheral blood of RAD patients showed increased numbers of cells expressing CD3, CD4, CD83, and CD86. CD4 to CD8 ratio was 8.3 6 1.4 (RAD) to 3.4 6 0.9 (normal; P,0.001). No differences were found in CD25, CD8, and S100 among groups. Postmortem samples from RAD showed increased CD3+, CD4+, CD86+, and S100+ cells, whereas CD25+ and CD8+ were unmodified between groups. CD4+ to CD8+ ratio was higher in the RAD PM group.Conclusions These results are consistent with an increased expression of immune cell markers in early RAD. Additional studies will explore if they may potentially turn into treatment targets to prevent disease progression.

A dipeptidyl peptidase-4 inhibitor, sitagliptin, exerts anti-inflammatory effects in type 2 diabetic patients

“…Therefore, the pro-inflammatory/anti-inflammatory cytokines in monocyte/macrophage may play an important role in atherosclerosis of type 2 diabetic patients. Several lines of evidence suggest that circulating monocytes, precursors of macrophages, display heterogeneity in mice and humans, and its cell heterogeneity influences plaque formation and inflammatory phenotypes of macrophages in adipose tissue and atherosclerotic lesion [15][16][17][18][19]. Swirski FK et al also reported Ly-6C hi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata in mice [20].…”

Renal artery stenosis

“…One must recognize, however, that atherosclerosis is a systemic disorder characterized by activation of multiple inflammatory pathways. Studies of vessels in patients with early ARVD indicate disturbances in both tissue and circulating inflammatory cell types, even before hypertension or parenchymal kidney injury are apparent (8). Recent studies also implicate immune mechanisms in driving experimental hypertension and its target manifestations (9).…”

Paradigm Shifts in Atherosclerotic Renovascular Disease

“…Studies in human atherosclerotic renovascular lesions indicate that subclinical lesions already have localization of inflammatory T-regulatory cells within vessel walls and modification of T cell-associated cytokine release even before reaching critical hemodynamic occlusion. 19 In other patients, segmental vascular occlusion is related to localized dissection and/or shelving of calcified debris that may be unrelated to inflammatory processes altogether. It should not be surprising that effects of large-vessel occlusive lesions may have widely variable effects on arterial pressure regulation and poststenotic processes within the kidney.…”