Increased circulating inflammatory endothelial cells in blacks with essential hypertension

Abstract

Morbidity and mortality attributable to hypertension are higher in black essential hypertensive (EH) compared with white EH patients, possibly related to differential effects on vascular injury and repair. Although circulating endothelial progenitor cells (EPCs) preserve endothelial integrity, inflammatory endothelial cells (IECs) detach from sites of injury and represent markers of vascular damage. We hypothesized that blood levels of IECs and inflammatory markers would be higher in black EH compared with white EH patients. Inferior vena cava and renal vein levels of CD34+/KDR+ (EPC) and VAP-1+ (IEC) cells were measured by fluorescence-activated cell sorting in white EH and black EH patients under fixed sodium intake and blockade of the renin-angiotensin system, and compared with systemic levels in normotensive control subjects (n=19 each). Renal vein and inferior vena cava levels of inflammatory cytokines and EPC homing factors were measured by Luminex. Blood pressure, serum creatinine, lipids, and antihypertensive medications did not differ between white and black EH patients, and EPC levels were decreased in both. Circulating IEC levels were elevated in black EH patients, and inversely correlated with EPC levels (R(2)=0.58; P=0.0001). Systemic levels of inflammatory cytokines and EPC homing factors were higher in black EH compared with white EH patients, and correlated directly with IECs. Renal vein inflammatory cytokines, EPCs, and IECs did not differ from their circulating levels. Most IECs expressed endothelial markers, fewer expressed progenitor cell markers, but none showed lymphocyte or phagocytic cell markers. Thus, increased release of cytokines and IECs in black EH patients may impair EPC reparative capacity and aggravate vascular damage, and accelerate hypertension-related complications.

Keywords: blacks; hypertension; inflammation; progenitor cells.

Figure 1

A: Representative flow cytometric dot plots for CD34+/KDR+ endothelial progenitor cells (EPC) and VAP-1+ inflammatory endothelial cells (IEC) and quantification of their inferior-vena-cava (IVC) and renal-vein (RV) levels in healthy volunteers (HV), Caucasian essential hypertensive (EH) and African American essential hypertensive (AAEH) patients. B: Systemic levels of IEC inversely correlated with circulating EPC levels in AAEH patients (E). *p≤0.05 vs. HV, ‡p≤0.05 vs.EH.

Figure 2

Systemic levels of soluble E selectin (sE Selectin), myeloperoxidase (MPO), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1 delta (MIP-1δ) correlated directly with the number of circulating inflammatory endothelial cells (IEC, A, C, E, G), but inversely with the number of circulating endothelial progenitor cells (EPC, B, D, F, H).