Age‐related impairment of endothelial progenitor cell migration correlates with structural alterations of heparan sulfate proteoglycans

Abstract

SummaryAging poses one of the largest risk factors for the development of cardiovascular disease. The increased propensity toward vascular pathology with advancing age maybe explained, in part, by a reduction in the ability of circulating endothelial progenitor cells to contribute to vascular repair and regeneration. Although there is evidence to suggest that colony forming unit-Hill cells and circulating angiogenic cells are subject to ageassociated changes that impair their function, the impact of aging on human outgrowth endothelial cell (OEC) function has been less studied. We demonstrate that OECs isolated from cord blood or peripheral blood samples from young and old individuals exhibit different characteristics in terms of their migratory capacity. In addition, age-related structural changes were discovered in OEC heparan sulfate (HS), a glycocalyx component that is essential in many signalling pathways. An age-associated decline in the migratory response of OECs toward a gradient of VEGF significantly correlated with a reduction in the relative percentage of the trisulfated disaccharide, 2-O-sulfated-uronic acid, N, 6-O-sulfated-glucosamine (UA[2S]-GlcNS[6S]), within OEC cell surface HS polysaccharide chains. Furthermore, disruption of cell surface HS reduced the migratory response of peripheral blood-derived OECs isolated from young subjects to levels similar to that observed for OECs from older individuals. Together these findings suggest that aging is associated with alterations in the fine structure of HS on the cell surface of OECs. Such changes may modulate the migration, homing, and engraftment capacity of these repair cells, thereby contributing to the progression of endothelial dysfunction and age-related vascular pathologies.

Age-Dependent Changes in Heparan Sulfate in Human Bruch's Membrane: Implications for Age-Related Macular Degeneration

“…[55][56][57][58] Here, we have seen that such variations can occur within two tissues that are closely positioned (i.e., in the BrM and NSR); this is consistent with the differential distribution of GAG epitopes present within these regions of the human eye that we mapped using phagedisplay antibodies. 34 There also is evidence that HS in particular tissues may undergo gradual changes with age.…”

Neovascularization Potential of Blood Outgrowth Endothelial Cells From Patients With Stable Ischemic Heart Failure Is Preserved

“…Specific reports on BOEC functionality and proliferation potential in various other disease states are, however, not uniform. Functional impairment has been reported, related to age,28 type 2 diabetes,29 obesity,30 pulmonary arterial hypertension,31 and smoking/chronic obstructive pulmonary disease 32. On the other hand, previous reports in treated coronary artery disease26, 33, 34 and arterial hypertension35 documented similar BOEC functionality in comparison to healthy controls.…”

Sulodexide Slows Down the Senescence of Aortic Endothelial Cells Exposed to Serum from Patients with Peripheral Artery Diseases

“…Damage to the endothelial glycocalyx is an important factor initiating the process of atherosclerosis [13]. It was shown that the age-related reduced ability of the endothelial progenitor cells to migrate is linked with the alteration in the structure of heparan sulphate proteoglycans located in the glycocalyx [14]. Previously, we found that sulodexide, which is a mixture of low molecular weight heparin and dermatan sulphate, reduces the senescence of human venous endothelial cells in in vitro conditions [15].…”