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THE ANTI‐ANGIOGENIC ACTIVITY OF rPAI‐1 23 INHIBITS ANGIOGENIC VASA VASORUM AND ATHERSCLEROTIC PLAQUE GROWTH
Author(s) -
MulliganKehoe Mary Jo,
Drinane Mary C,
Mollmark Jessica I.,
Simons Michael
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a16-d
Subject(s) - vasa vasorum , saline , lumen (anatomy) , angiogenesis , apolipoprotein b , aorta , medicine , endocrinology , cholesterol
: Neovascularized areas in atherosclerosis are primarily supplied by angiogenic vasa vasorum. The vasa vasorum density increases during plaque progression, but the role of angiogenesis in plaque growth is uncertain. A truncated PAI‐1 protein, rPAI‐1 23 , has significant anti‐angiogenic activity. We hypothesized that rPAI‐1 23 inhibition of angiogenic vasa vasorum in atherogenic mice would reduce plaque progression. Methods : Female LDLR −/− /ApoB‐100 mice were fed a high fat diet (HFD) for 14 weeks prior to initiating 6 weeks of rPAI‐1 23 (n= 16) or saline (n=11) treatment with continued HFD. Control animals received chow diet and saline treatment. Lipid content, vasa vasorum density, vessel circumference, plaque and lumen areas were measured. Results : rPAI‐1 23 reduced lipid area by 60% and 30% (p<0.001) in the descending aorta and aortic root, respectively as compared to HFD saline treatment. Measurements of reconstructed vessels in the plaque area show that rPAI‐1 23 decreased vessel area and length by 43 and 37% (p = 0.01), respectively. Carotid artery circumferences in rPAI‐1 23 and saline HFD groups were similar. However, rPAI‐1 23 decreased plaque area by 67% (p<0.001) and increased lumen area by 74% (p<0.001). Conclusions : rPAI‐1 23 inhibits angiogenic vasa vasorum, reduces plaque growth and promotes plaque regression in atherogenic female LDLR −/− /ApoB‐100 mice.