High glucose-induced alterations in subendothelial matrix perlecan leads to increased monocyte binding.
OBJECTIVE
Hyperglycemia is an independent risk factor for cardiovascular disease in diabetic patients, although the link between the two is unknown. These studies were designed to model effects of high glucose on an early event in atherogenesis: the binding of monocytes to subendothelial matrix (SEM).


RESULTS
SEM was prepared from human aortic endothelial cells (HAECs) and bovine aortic endothelial cells (BAECs) cultured in the presence of low (5 mmol/L) or high (30 mmol/L) glucose for 3 to 5 days. Monocyte binding was significantly higher (P<0.05) to the SEM of both HAEC and BAEC exposed to high glucose. This increase was a result of changes in SEM heparan sulfate proteoglycans (HSPGs). Metabolic radiolabeling of BAEC demonstrated a 24% decrease in [35S]sulfate incorporation into SEM HSPG produced by cells incubated in 30 mmol/L versus 5 mmol/L glucose, whereas no glucose-associated differences were measured in [35S]methionine incorporation into proteoglycans (PGs) or non-PG proteins. Autoradiography revealed 2 high-molecular weight SEM HSPGs. One was a hybrid PG that contained both heparan sulfate and chondroitin sulfate/dermatan sulfate chains. Both PGs were identified by Western blotting as perlecan.


CONCLUSIONS
These results illustrate that hyperglycemia-induced structural changes in perlecan may result in a SEM that is more favorable to retention of monocytes.
Vogl-Willis
Catherine A
CA
Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Edwards
Iris J
IJ
D053674:Aggrecans; D000818:Animals; D001011:Aorta / Q000166:cytology; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000166:cytology*; D005109:Extracellular Matrix / Q000187:drug effects* / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000502:physiology; D005947:Glucose / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000502:physiology; D019812:Heparan Sulfate Proteoglycans / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D037181:Lectins, C-Type; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D011509:Proteoglycans / Q000502:physiology; D013431:Sulfates / Q000378:metabolism
D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans; D019812:Heparan Sulfate Proteoglycans; D037181:Lectins, C-Type; D011509:Proteoglycans; D013431:Sulfates; C071927:perlecan; D005947:Glucose