Title

Partial ligation-induced carotid artery occlusion induces leukocyte recruitment and lipid accumulation-A shear stress model of atherosclerosis

Authors

Authors

H. Merino; S. Parthasarathy;D. K. Singla

Comments

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Abbreviated Journal Title

Mol. Cell. Biochem.

Keywords

Atherosclerosis; Pro-inflammatory cytokines; Shear stress; Carotid; artery; HUMAN CORONARY-ARTERIES; FAMILIAL HYPERCHOLESTEROLEMIA; ENDOTHELIAL; DYSFUNCTION; DISTURBED FLOW; MOUSE; PLAQUE; PROGRESSION; THICKNESS; PATTERNS; BEHAVIOR; Cell Biology

Abstract

Recent studies suggest that disturbed blood flow-induced shear stress can induce atherosclerosis (ATH) in humans and animals without a high fat diet. Therefore, we hypothesize that partial ligation of the left carotid artery can generate disturbed blood flow and shear stress and would lead to ATH in a predisposed genetic model of Apo E-/- mice. The partial left carotid artery model was generated by ligating three out of four branches of the left carotid artery compared with controls which experienced similar surgery conditions but no ligation. Animals were sacrificed 2 weeks post-ligation and examined for plaque formation, infiltration of leukocytes, pro-inflammatory immune response, and blood flow velocity. Our findings suggest a significant (p < 0.05) increase in plaque formation and lipid deposition in the partial ligated animals compared with controls, confirmed with hematoxylin and eosin and oil red O staining. Furthermore, there was a significant (p < 0.05) increase in the number of M1 macrophages and release of pro-inflammatory cytokines, IL-6 and TNF alpha, as compared with the control. Moreover, partial ligated carotid arteries demonstrated disturbed blood flow as their systolic velocity was significantly reduced. In conclusion, our data suggest that partial ligation of the left carotid artery induces disturbed flow and shear stress in the predisposed genetic model of Apo E-/- mice and leads to significantly developed ATH. Similarities to clinical patients who develop ATH independent of a high fat diet show that this could be a potential animal model to examine various parameters in ATH.

Journal Title

Molecular and Cellular Biochemistry

Volume

372

Issue/Number

1-2

Publication Date

1-1-2013

Document Type

Article

Language

English

First Page

267

Last Page

273

WOS Identifier

WOS:000312130500029

ISSN

0300-8177

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