Circulating endothelial progenitor cells, endothelial function, carotid intima–media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria

Abstract

Aims/hypothesis Type 1 diabetes is associated with premature arterial disease. Bone-marrow derived, circulating endothelial progenitor cells (EPCs) are believed to contribute to endothelial repair. The hypothesis tested was that circulating EPCs are reduced in young people with type 1 diabetes without vascular injury and that this is associated with impaired endothelial function and increased carotid intima-media thickness (CIMT). Methods We compared 74 people with type 1 diabetes with 80 healthy controls. CD34, CD133, vascular endothelial (VE) growth factor receptor-2 (VEGFR-2) and VE-cadherin antibodies were used to quantify EPCs and progenitor cell subtypes using flow-cytometry. Ultrasound assessment of endothelial function by brachial artery flow-mediated dilatation (FMD) and CIMT was made. Circulating endothelial markers, inflammatory markers and plasma plasminogen activator inhibitor-1 (PAI-1) levels were measured. Results CD34+VE-cadherin+, CD133+VE-cadherin+ and CD133+VEGFR-2+ EPC counts were significantly lower in people with diabetes (46-69%; p=0.004-0.043). In people with type 1 diabetes, FMD was reduced by 45% (p<0.001) and CIMT increased by 25% (p<0.001), these being correlated (r=−0.25, p=0.033). There was a significant relationship between FMD and CD34+VE-cadherin+ (r = 0.39, p = 0.001), CD133+VEGFR-2+ (r =0.25, p = 0.037) and CD34+ (r=0.34, p=0.003) counts. Circulating high-sensitivity C-reactive protein, PAI-1, interleukin-6 and E-selectin were significantly higher in the diabetes group (p < 0.001 to p = 0.049), the last two of these correlating with FMD (r=−0.27, p=0.028 and r=−0.24, p=0.048, respectively). Conclusions/interpretation These findings suggest that abnormalities of endothelial function in addition to proinflammatory and pro-thrombotic states are already common in people with type 1 diabetes before development of clinically evident arterial damage. Low EPC counts confirm risk of macrovascular complications and may account for impaired endothelial function and predict future cardiovascular events.

Evaluation of biochemical and clinical markers of endothelial dysfunction and their correlation with urinary albumin excretion in patients with type 1 diabetes mellitus

“…sICAM-1 was significantly higher in diabetics compared to control subjects but there wasn't any difference between diabetic subgroups. In the study of Sibal and cols., sICAM1 was significantly higher in T1DM patients compared to controls supporting our results (24). Bruno and cols.…”

“…This hypothesis is supported by Sibal and cols. who demonstrated that FMD was reduced by % 45 in patients with T1DM without any complications compared to controls (24). Endothelin-1 is a marker of ED and plays role in angiogenesis, fibrosis, inflammation and acts as a vasopressor agent causing HT (25).…”

Endothelial-Regenerating Cells

“…Other than ex vivo cultivation of (purified) blood samples, flow-cytometric analysis of multilabeled blood samples has become a method of choice. 32,[43][44][45][46][47] Detecting untouched EPCs within the in vivo situation ideally in the progeny status with initial EC features is the basic idea of choosing flow cytometry. Among the various surface markers (Table), CD34 and KDR have turned out to be the most popular combination in humans (and Sca-1 and Flk-1, the murine homolog of KDR, in rodents).…”

Endothelial Progenitor Cells: New Targets to Control Autoimmune Disorders

“…However before comparisons can be made between studies, it is important to consider the methods used to quantify EPC numbers in these studies. Circulating EPC numbers were quantified either by surface antigen expression on peripheral blood mononuclear cells (PBMNCs) (Brunner et al, 2009, Sibal et al, 2009, through the culture of early-outgrowth EPC colonies (Asnaghi et al, 2006) or through the uptake of acetylated LDL and binding of UEA-l to cultured PBMNCs (Loomans et al, 2004). To the best of our knowledge, there are currently no reports on the correlation between T1DM and the growth of late-outgrowth EPCs.…”