Wall shear stress and strain modulate experimental aneurysm cellularity.
OBJECTIVE
Clinical evidence indicates that hemodynamic conditions influence abdominal aortic aneurysm (AAA) disease. We modified blood flow to evaluate the effects of wall shear stress (WSS) and relative wall strain (RWS) on aneurysm structure and cellularity.


METHODS
Rodent AAAs were created with porcine pancreatic elastase infusion. In group 1 AAA WSS was increased with left femoral arteriovenous fistula creation, whereas in group 2 AAA WSS was decreased with left iliac artery ligation. Aortic flow, wall motion, and blood pressure were recorded in both groups. AAA diameter, endothelial and smooth muscle cellularity (CD31 and alpha-smooth muscle actin immunostaining), markers for cell proliferation (5-bromodeoxyuridine), endothelial and smooth muscle cell growth factor production (vascular endothelial growth factor-D and platelet-derived growth factor-beta, respectively), and apoptosis (deoxyuridine triphosphate nick end-labeled [TUNEL] stain) were compared between groups when the animals were killed.


RESULTS
Arteriovenous fistula creation increased WSS (high-flow AAA) by 300% and RWS by 150%. Iliac ligation reduced WSS (low-flow AAA) by 60%. Neither procedure significantly altered systolic, diastolic, or mean aortic pressure. When the animals were killed 7 days after elastase infusion, low-flow AAAs were significantly larger than high-flow AAAs. High-flow AAAs also contained more endothelial cells and smooth muscle cells, and evidence of increased growth factor production, cell proliferation, and decreased apoptosis. No difference in type or severity of AAA inflammatory cell infiltrate was noted between groups.


CONCLUSIONS
High flow conditions stimulate endothelial cell and smooth muscle cell proliferation in experimental aneurysms. Enhanced cellularity may stabilize aortic integrity, limiting aneurysm growth. Increased lower extremity activity may prevent or retard AAA disease through salutary effects on aortic remodeling mediated by endothelial cells and smooth muscle cells.
Hoshina
Katsuyuki
K
Division of Vascular Surgery, Stanford University, Palo Alto, Calif, USA.
Sho
Eiketsu
E
Sho
Mien
M
Nakahashi
Takeshi K
TK
Dalman
Ronald L
RL
D000818:Animals; D001012:Aorta, Abdominal / Q000166:cytology* / Q000378:metabolism / Q000503:physiopathology*; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism / Q000503:physiopathology*; D001783:Blood Flow Velocity / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004549:Elastin / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology*; D008955:Models, Cardiovascular; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis; D033081:Shear Strength; D042643:Vascular Endothelial Growth Factor D
D016228:Endothelial Growth Factors; D042643:Vascular Endothelial Growth Factor D; D003094:Collagen; D004549:Elastin; D040262:Receptors, Vascular Endothelial Growth Factor