title: Effects of some anti-diabetic and cardioprotective agents on proliferation and apoptosis of human coronary artery endothelial cells.
abstract: BACKGROUND
  The leading cause of death for patients suffering from diabetes is macrovascular disease. Endothelial dysfunction is often observed in type 2 diabetic patients and it is considered to be an important early event in the pathogenesis of atherogenesis and cardiovascular disease. Many drugs are clinically applied to treat diabetic patients. However, little is known whether these agents directly interfere with endothelial cell proliferation and apoptosis. This study therefore aimed to investigate how anti-diabetic and cardioprotective agents affect human coronary artery endothelial cells (HCAECs).
  
  
  METHODS
  The effect of anti-diabetic and cardioprotective agents on HCAEC viability, proliferation and apoptosis was studied. Viability was assessed using Trypan blue exclusion; proliferation in 5 mM and 11 mM of glucose was analyzed using [3H]thymidine incorporation. Lipoapoptosis of the cells was investigated by determining caspase-3 activity and the subsequent DNA fragmentation after incubation with the free fatty acid palmitate, mimicking diabetic lipotoxicity.
  
  
  RESULTS
  Our data show that insulin, metformin, BLX-1002, and rosuvastatin improved HCAEC viability and they could also significantly increase cell proliferation in low glucose. The proliferative effect of insulin and BLX-1002 was also evident at 11 mM of glucose. In addition, insulin, metformin, BLX-1002, pioglitazone, and candesartan significantly decreased the caspase-3 activity and the subsequent DNA fragmentation evoked by palmitate, suggesting a protective effect of the drugs against lipoapoptosis.
  
  
  CONCLUSIONS
  Our results suggest that the anti-diabetic and cardioprotective agents mentioned above have direct and beneficial effects on endothelial cell viability, regeneration and apoptosis. This may add yet another valuable property to their therapeutic effect, increasing their clinical utility in type 2 diabetic patients in whom endothelial dysfunction is a prominent feature that adversely affect their survival.
authors.affiliation: Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm SE-11883, Sweden. qmnzhang@yahoo.com
authors.forename: Linnéa
authors.initials: L
authors.lastname: Eriksson
authors.forename: Ozlem
authors.initials: O
authors.lastname: Erdogdu
authors.forename: Thomas
authors.initials: T
authors.lastname: Nyström
authors.forename: Qimin
authors.initials: Q
authors.lastname: Zhang
authors.forename: Åke
authors.initials: Å
authors.lastname: Sjöholm
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002316:Cardiotonic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology* / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects*; D005464:Fluorobenzenes / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D008687:Metformin / Q000494:pharmacology; D000077205:Pioglitazone; D011743:Pyrimidines / Q000494:pharmacology; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: C542815:BLX 1002; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002316:Cardiotonic Agents; D005464:Fluorobenzenes; D007004:Hypoglycemic Agents; D007328:Insulin; D011743:Pyrimidines; D013449:Sulfonamides; D013777:Tetrazoles; D045162:Thiazolidinediones; D000068718:Rosuvastatin Calcium; D008687:Metformin; D005947:Glucose; C081643:candesartan; D000077205:Pioglitazone