PMID- 28207427
OWN - NLM
STAT- MEDLINE
DCOM- 20180105
LR  - 20220331
IS  - 1533-4023 (Electronic)
IS  - 0160-2446 (Linking)
VI  - 69
IP  - 5
DP  - 2017 May
TI  - Progression and Characterization of the Accelerated Atherosclerosis in Iliac 
      Artery of New Zealand White Rabbits: Effect of Simvastatin.
PG  - 314-325
LID - 10.1097/FJC.0000000000000477 [doi]
AB  - OBJECTIVE: Although atherosclerosis is described in New Zealand White rabbit's 
      iliac artery, yet details of time-dependent atherosclerosis progression are not 
      well known. Further, a well characterized accelerated model of atherosclerosis is 
      also required for the screening of candidate drugs to target specific steps of 
      atherosclerosis development. The present study extensively characterizes the 
      time-dependent plaque composition and functional responses of the atherosclerosis 
      in rabbit iliac artery and its modification by simvastatin. METHODS: 
      Atherosclerosis was induced with a combination of balloon injury and atherogenic 
      diet (AD) (1% cholesterol, 6% peanut oil) in rabbit's iliac artery. 
      Atherosclerosis progression was evaluated on days 8, 10, 15, 21, 35, and 56 after 
      AD feeding. The plaque characterization was done using histology, real-time 
      reverse transcription-polymerase chain reaction, and vasoreactivity experiments. 
      The standard anti-hyperlipidemic drug, simvastatin (5 mg.kg.d), was used to 
      investigate its effect on atherosclerotic changes. RESULTS: Plasma lipids were 
      elevated in a progressive manner after AD feeding from days 8 to 56. Similarly, 
      arterial lipids, Monocyte Chemoattractant Protein-1 (MCP-1) level along with 
      infiltration of macrophages in the lesion area were also increased from day 15 
      onward. This resulted in a significant increase in the plaque area and 
      intimal-medial thickness ratio in contrast to normal animals. Inflammatory milieu 
      was observed with a significant increase in expression of pro-inflammatory 
      regulators like MCP-1, Tumor Necrosis Factor-alpha (TNF-alpha) and Vascular Cell Adhesion 
      Molecule-1 (VCAM-1), whereas anti-inflammatory cytokine interleukin 10 decreased 
      as disease progressed. Endothelial dysfunction was also observed, specifically 
      Acetylcholine (ACh)-induced vasorelaxation was reduced from day 8 onward, whereas 
      the phenylephrine-induced vasoconstriction response was progressively reduced 
      from day 15 in the iliac artery. Ground substances including proteoglycans, 
      alpha-actin, and collagen content along with metalloproteinase-9 and Tissue inhibitor 
      of metalloproteinases-1 (TIMP-1) inhibitors were significantly augmented at later 
      time points, day 21 onward. Simvastatin treatment for 35 days, at a dose having 
      no significant effect on plasma lipid levels, significantly reduced 
      atherosclerotic progression as evident by reduced macrophage content, 
      inflammatory burden, and extracellular matrix component like proteoglycans and 
      metalloproteinase-9. CONCLUSIONS: The authors observed that AD feeding with 
      balloon injury in the rabbit iliac artery accelerated the progression of 
      atherosclerosis and exhibited predominant features of type III human lesion 
      within 8 weeks (56 days). Simvastatin treatment for 35 days exhibited 
      anti-atherosclerotic efficacy without significantly lowering the circulating 
      lipids. The current study thus provides an insight into the time-dependent 
      atherosclerotic progression in rabbit iliac artery and highlights its utility for 
      anti-atherosclerotic evaluation of the candidate drugs.
FAU - Kanshana, Jitendra S
AU  - Kanshana JS
AD  - Pharmacology Division, Council of Scientific and Industrial Research-Central Drug 
      Research Institute, Lucknow, India.
FAU - Khanna, Vivek
AU  - Khanna V
FAU - Singh, Vishal
AU  - Singh V
FAU - Jain, Manish
AU  - Jain M
FAU - Misra, Ankita
AU  - Misra A
FAU - Kumar, Sachin
AU  - Kumar S
FAU - Farooqui, Mariya
AU  - Farooqui M
FAU - Barthwal, Manoj K
AU  - Barthwal MK
FAU - Dikshit, Madhu
AU  - Dikshit M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Cardiovasc Pharmacol
JT  - Journal of cardiovascular pharmacology
JID - 7902492
RN  - 0 (Biomarkers)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipids)
RN  - AGG2FN16EV (Simvastatin)
SB  - IM
MH  - Angioplasty, Balloon
MH  - Animals
MH  - Atherosclerosis/blood/*drug therapy/pathology/physiopathology
MH  - Biomarkers/blood
MH  - Diet, High-Fat
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Endothelium, Vascular/drug effects/physiopathology
MH  - Extracellular Matrix/metabolism
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology
MH  - Iliac Artery/*drug effects/metabolism/pathology/physiopathology
MH  - Inflammation Mediators/blood
MH  - Lipids/blood
MH  - Macrophages/drug effects/metabolism
MH  - Male
MH  - *Plaque, Atherosclerotic
MH  - Rabbits
MH  - Simvastatin/*pharmacology
MH  - Time Factors
MH  - Vascular Remodeling/drug effects
MH  - Vasoconstriction/drug effects
MH  - Vasodilation/drug effects
EDAT- 2017/02/17 06:00
MHDA- 2018/01/06 06:00
CRDT- 2017/02/17 06:00
PHST- 2017/02/17 06:00 [pubmed]
PHST- 2018/01/06 06:00 [medline]
PHST- 2017/02/17 06:00 [entrez]
AID - 10.1097/FJC.0000000000000477 [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol. 2017 May;69(5):314-325. doi: 
      10.1097/FJC.0000000000000477.