Dynamic observation of mechanically-injured mouse femoral artery reveals an antiinflammatory effect of renin inhibitor.

Abstract

OBJECTIVE:

The renin-angiotensin-aldosterone system (RAS) plays a central role in atherosclerosis. To investigate the effects of a direct renin inhibitor aliskiren on vascular inflammation, we conducted leukocyte adhesion assays in vivo and in vitro using a novel real-time imaging system.

METHODS AND RESULTS:

Aliskiren (10 mg/kg/d) or PBS was administered to C57BL/6 mice (6-7 weeks of age; Oriental Yeast, Tokyo, Japan) for 2 weeks via an osmotic pump. Blood pressure was not significantly changed in the 2 groups throughout the experimental period. A perivascular cuff injury was then introduced to the femoral artery and real-time intravital microscopic observation was conducted 24 hours after injury. The number of adherent leukocytes was elevated in the injured mice without aliskiren (43.8+/-9.3/10(-2) mm(2)), whereas that was significantly reduced in the mice with aliskiren (18.4+/-4.4, P<0.05). Treatment of human umbilical vein endothelial cells (HUVECs) with aliskiren significantly reduced the adhesion of THP-1 cells to TNF-alpha-activated HUVECs (P<0.05). Interestingly, TNF-alpha-induced renin activity and angiotensin II production in HUVECs were also blunted by aliskiren. Furthermore, exogenous renin and angiotensin II abrogated the aliskiren-mediated reduction of THP-1 cell adhesion to HUVECs.

CONCLUSIONS:

Our in vivo and in vitro findings indicate a pivotal role for renin inhibition in vascular inflammation independent of blood pressure.

• Authors: Jun Ino, Chiari Kojima, Mizuko Osaka, Kosaku Nitta, Masayuki Yoshida
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 29 Issue 11 Pg. 1858-63 (Nov 2009) ISSN: 1524-4636 [Electronic] United States
• PMID: 19778947 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amides
• Fumarates
• Reactive Oxygen Species
• Tumor Necrosis Factor-alpha
• aliskiren
• Renin

Topics

• Amides (pharmacology)
• Animals
• Blotting, Western
• Cells, Cultured
• Disease Models, Animal
• Endothelial Cells (cytology, drug effects)
• Femoral Artery (drug effects, injuries)
• Fumarates (pharmacology)
• Humans
• In Vitro Techniques
• Mice
• Mice, Inbred C57BL
• Oxidative Stress (physiology)
• Random Allocation
• Reactive Oxygen Species (metabolism)
• Renin (antagonists & inhibitors)
• Renin-Angiotensin System (drug effects, physiology)
• Reverse Transcriptase Polymerase Chain Reaction
• Sensitivity and Specificity
• Tumor Necrosis Factor-alpha (pharmacology)