title: Cholesterol diet withdrawal leads to an initial plaque instability and subsequent regression of accelerated iliac artery atherosclerosis in rabbits.
abstract: Effect of long term cholesterol diet withdrawal on accelerated atherosclerosis in iliac artery of New Zealand White (NZW) rabbits has not been explored so far. Atherosclerosis was thus induced in rabbits by a combination of balloon injury and atherogenic diet (AD) (1% cholesterol and 6% peanut oil) feeding for 8 weeks (baseline) followed by chow diet (CD) feeding for 4, 8, 16, 32, 50 and 64 weeks. The plaque characterization was done using histology, real time RT-PCR and vasoreactivity studies. Significant elevation in plasma lipids with AD feeding was normalized following 16 weeks of CD feeding. However, baseline comparison showed advanced plaque features even after 8 weeks of CD period with significant elevation in intima/media thickness ratio and plaque area later showing reduction at 50 and 64 weeks CD periods. Lesion lipid accumulation and CD68 positivity was maintained till 16 weeks of CD feeding which significantly reduced from 32 to 64 weeks CD periods. Baseline comparison showed significant increase in ground substance, MMP-9 and significant decrease in α-actin and collagen content at 8 weeks CD period indicating features of unstable plaque. These features regressed up to 64 weeks of CD. Partial restoration of functional vasoconstriction and vasorelaxation was seen after 64 weeks of CD feeding. mRNA expression of MCP-1, VCAM-1, collagen type I and III, MMP-9, TIMP-1, IFN-γ, TNF-α, IL-10 and eNOS supported the above findings. The study thus reveals insights into initial plaque instability and subsequent regression on AD withdrawal in this model. These results are suggestive of an appropriate window for drug intervention for plaque stability/regression and restenosis as well as improves understanding of plaque regression phenomenon in this model.
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute, B.S. 10/1, Sector 10, Jankipuram Extension, Lucknow, Uttar Pradesh, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Khanna
authors.forename: Manish
authors.initials: M
authors.lastname: Jain
authors.forename: Vishal
authors.initials: V
authors.lastname: Singh
authors.forename: Jitendra S
authors.initials: JS
authors.lastname: Kanshana
authors.forename: Prem
authors.initials: P
authors.lastname: Prakash
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Barthwal
authors.forename: Puvvada S R
authors.initials: PS
authors.lastname: Murthy
authors.forename: Madhu
authors.initials: M
authors.lastname: Dikshit
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D050197:Atherosclerosis / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004036:Diet, Atherogenic; D018450:Disease Progression; D005487:Foam Cells / Q000473:pathology; D007083:Iliac Artery / Q000473:pathology* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000473:pathology*; D011817:Rabbits
chemical_list: D000199:Actins; D015815:Cell Adhesion Molecules; D002791:Cholesterol, Dietary; D016207:Cytokines; D018836:Inflammation Mediators; D008055:Lipids; D003094:Collagen; D020780:Matrix Metalloproteinase 9