PMID- 16337042
OWN - NLM
STAT- MEDLINE
DCOM- 20060321
LR  - 20220309
IS  - 0167-5273 (Print)
IS  - 0167-5273 (Linking)
VI  - 106
IP  - 3
DP  - 2006 Jan 26
TI  - Favourable modulation of the inflammatory changes in hypercholesterolemic 
      atherogenesis by a low-molecular-weight heparin derivative.
PG  - 338-47
AB  - BACKGROUND: In the hypercholesterolemic state, the net result of combined 
      oxidative and nitrosative stress is a pro-inflammatory phenotype that is 
      manifested as increased adhesion molecule expression, enhanced leucocyte 
      trafficking, and increased vascular permeability. The present work explores the 
      inflammatory aspects of hypercholesterolemic atherogenesis, and also evaluates 
      the role of a low-molecular-weight heparin derivative (LMWH), Certoparin, on a 
      biochemical basis. METHODS AND RESULTS: Two groups of male Wistar rats were fed 
      an atherogenic diet (normal rat chow plus 4% cholesterol, 1% cholic acid and 0.5% 
      thiouracil-CCT diet) for 2 weeks. While one was left untreated, the other was 
      administered LMWH (300 microg/day/rat commencing on day 8 and continued for a 
      week). Increased concentrations of plasma C-reactive protein and fibrinogen and 
      cardiac TNF-alpha indicated severe inflammation in the atherogenic diet fed rats. 
      In comparison, these biochemical indices of inflammation diminished significantly 
      in the LMWH treated group (p < 0.001). Significant depletion of thiols, along 
      with accentuated activities of the glutathione metabolising was observed in the 
      cardiac and hepatic tissues of the untreated atherogenic rats, indicating 
      heightened oxidative response. Tissue damage was marked by elevated levels of 
      plasma and tissue hexose, hexosamine, hexuronic acid and sialic acid, which were 
      reversed towards normalcy on LMWH administration. The activities of lysosomal 
      enzymes (N-acetyl glucosaminidase, beta-glucuronidase, beta-galactosaminidase and 
      cathepsin-D) showed a marked increase in the CCT-diet fed rats, while LMWH 
      treated rats showed normal activities (p < 0.001). The osmotic fragility test 
      revealed that the untreated hyperlipidemic rat erythrocytes were significantly 
      fragile at high salt concentrations, while the response was normalized in the 
      LMWH treated group (p < 0.05). Further, hypercholesterolemia induced 
      downregulation of physiological nitric oxide levels was corrected upon treatment 
      with heparin-derivative. CONCLUSION: The results of this work highlight the 
      inflammatory changes in atherogenic conditions and that the low-molecular-weight 
      heparin derivative affords substantial protection.
FAU - Deepa, P R
AU  - Deepa PR
AD  - Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic 
      Medical Sciences, University of Madras, Taramani, Chennai 600 113, India. 
      dipa_pr@mailcity.com
FAU - Varalakshmi, P
AU  - Varalakshmi P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Int J Cardiol
JT  - International journal of cardiology
JID - 8200291
RN  - 0 (Anticoagulants)
RN  - 0 (Biomarkers)
RN  - 0 (Blood Proteins)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - V72OT3K19I (certoparin)
SB  - IM
MH  - Animals
MH  - Anticoagulants/*pharmacology
MH  - Atherosclerosis/blood/*immunology
MH  - Biomarkers/blood
MH  - Blood Proteins/analysis/drug effects/*immunology
MH  - Disease Models, Animal
MH  - Heparin, Low-Molecular-Weight/*pharmacology
MH  - Hypercholesterolemia/blood/*immunology
MH  - Male
MH  - Oxidative Stress/drug effects
MH  - Rats
MH  - Rats, Wistar
EDAT- 2005/12/13 09:00
MHDA- 2006/03/22 09:00
CRDT- 2005/12/13 09:00
PHST- 2004/11/17 00:00 [received]
PHST- 2005/02/03 00:00 [revised]
PHST- 2005/02/06 00:00 [accepted]
PHST- 2005/12/13 09:00 [pubmed]
PHST- 2006/03/22 09:00 [medline]
PHST- 2005/12/13 09:00 [entrez]
AID - S0167-5273(05)00433-X [pii]
AID - 10.1016/j.ijcard.2005.02.012 [doi]
PST - ppublish
SO  - Int J Cardiol. 2006 Jan 26;106(3):338-47. doi: 10.1016/j.ijcard.2005.02.012.