PMID- 16644678
OWN - NLM
STAT- MEDLINE
DCOM- 20060626
LR  - 20220310
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 55
IP  - 5
DP  - 2006 May
TI  - Human vascular smooth muscle cells from diabetic patients are resistant to 
      induced apoptosis due to high Bcl-2 expression.
PG  - 1243-51
AB  - An emerging body of evidence suggests that vascular remodeling in diabetic 
      patients involves a perturbation of the balance between cell proliferation and 
      cell death. Our aim was to study whether arteries and vascular smooth muscle 
      cells (VSMCs) isolated from diabetic patients exhibit resistance to apoptosis 
      induced by several stimuli. Internal mammary arteries (IMAs) were obtained from 
      patients who had undergone coronary artery bypass graft surgery. Arteries from 
      diabetic patients showed increasing levels of Bcl-2 expression in the media 
      layer, measured by immunofluorescence and by Western blotting. Human IMA VSMCs 
      from diabetic patients showed resistance to apoptosis, measured as DNA 
      fragmentation and caspase-3 activation, induced by C-reactive protein (CRP) and 
      other stimuli, such as hydrogen peroxide and 7beta-hydroxycholesterol. The 
      diabetic cells also exhibited overexpression of Bcl-2. Knockdown of Bcl-2 
      expression with Bcl-2 siRNA in cells from diabetic patients reversed the 
      resistance to induced apoptosis. Consistent with the above, we found that 
      pretreatment of nondiabetic VSMCs with high glucose abolished the degradation of 
      Bcl-2 induced by CRP. Moreover, cell proliferation was increased in diabetic 
      compared with nondiabetic cells. This differential effect was potentiated by 
      glucose. We conclude that the data provide strong evidence that arterial 
      remodeling in diabetic patients results from a combination of decreased apoptosis 
      and increased proliferation.
FAU - Ruiz, Emilio
AU  - Ruiz E
AD  - Department of Pharmacology, School of Medicine, Universidad Complutense, 28040 
      Madrid, Spain.
FAU - Gordillo-Moscoso, Antonio
AU  - Gordillo-Moscoso A
FAU - Padilla, Eugenia
AU  - Padilla E
FAU - Redondo, Santiago
AU  - Redondo S
FAU - Rodriguez, Enrique
AU  - Rodriguez E
FAU - Reguillo, Fernando
AU  - Reguillo F
FAU - Briones, Ana M
AU  - Briones AM
FAU - van Breemen, Cornelis
AU  - van Breemen C
FAU - Okon, Elena
AU  - Okon E
FAU - Tejerina, Teresa
AU  - Tejerina T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 3OWL53L36A (Mannitol)
RN  - 9007-34-5 (Collagen)
RN  - 9007-58-3 (Elastin)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Aged
MH  - Apoptosis/*physiology
MH  - Collagen/analysis
MH  - Coronary Vessels/pathology/*physiopathology
MH  - Diabetic Angiopathies/genetics/physiopathology/*surgery
MH  - Elastin/analysis
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Glucose/pharmacology
MH  - Humans
MH  - Internal Mammary-Coronary Artery Anastomosis
MH  - Male
MH  - Mannitol/pharmacology
MH  - Middle Aged
MH  - Muscle, Smooth, Vascular/pathology/*physiopathology
MH  - Proto-Oncogene Proteins c-bcl-2/*genetics
EDAT- 2006/04/29 09:00
MHDA- 2006/06/27 09:00
CRDT- 2006/04/29 09:00
PHST- 2006/04/29 09:00 [pubmed]
PHST- 2006/06/27 09:00 [medline]
PHST- 2006/04/29 09:00 [entrez]
AID - 55/5/1243 [pii]
AID - 10.2337/db05-0949 [doi]
PST - ppublish
SO  - Diabetes. 2006 May;55(5):1243-51. doi: 10.2337/db05-0949.