Novel model of inflammatory neointima formation reveals a potential role of myeloperoxidase in neointimal hyperplasia.
Atherosclerosis, which is characterized by neointima formation, is an inflammatory disease. However, there is no inflammatory product-elicited neointimal model to support the causal role of inflammation in atherogenesis. We reported previously that leukocyte-derived MPO induces vascular injury responses such as endothelial dysfunction. We now test the role of MPO in inflammatory neointima formation. We infused temporarily isolated rat common carotid arteries with MPO (200 nM) and incubated for 1 h. We found that although MPO itself did not induce any neointima formation 2 wk after treatment, in the presence of its substrate, hydrogen peroxide, MPO was able to elicit neointimal hyperplasia. We further confirmed that MPO-induced neointimal hyperplasia is mediated by its product, hypochlorous acid (HOCl). HOCl elicited apoptosis both in intima and media followed by vascular proliferative response and resulted in neointima formation with a heterogeneous cell population. Both histological and functional features of HOCl-treated vessels are similar to those in atherosclerotic lesions. To our knowledge, this is the first direct in vivo demonstration of neointimal formation induced by a product of the inflammatory cascade. The results suggest that MPO may be a mediator for pathological neointima growth. This novel neointimal model could be useful for studying inflammation and atherosclerosis.
Yang
Jian
J
Vascular Biology Center and Dept. of Surgery, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Cheng
Yunhui
Y
Ji
Ruirui
R
Zhang
Chunxiang
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006997:Hypochlorous Acid / Q000378:metabolism / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D017540:Tunica Media / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*
D006997:Hypochlorous Acid; D009195:Peroxidase