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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1916.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Hemodynamic Regulation of CD34⁺ Cell Localization and Differentiation in Experimental Aneurysms

Eiketsu Sho; Mien Sho; Hiroshi Nanjo; Koichi Kawamura; Hirotake Masuda; Ronald L. Dalman

From the Division of Vascular Surgery (E.S., M.S., R.L.D.), Stanford University, and Surgical Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif; and the Second Department of Pathology (H.N., K.K., H.M.), Akita University School of Medicine, Akita, Japan.

Correspondence to Ronald L. Dalman, B3-119, 3801 Miranda Ave, VAPAHCS, Palo Alto, CA 94304. E-mail rld{at}stanford.edu

Objectives— Bone marrow-derived vascular progenitor cells (CD34⁺) are present in human and animal models of abdominal aortic aneurysm (AAA) disease. These preterminally differentiated cells may modulate disease resistance. We examined the influence of variable hemodynamic conditions on progenitor cell localization and differentiation in experimental AAAs.

Methods and Results— Murine AAAs were created via porcine pancreatic elastase (PPE) infusion. AAA blood flow was increased by aortocaval fistula (ACF) formation (HF-AAA), decreased via left iliac ligation (LF-AAA), or left unchanged (NF-AAA). ACF creation increased flow by 1700%, whereas iliac ligation decreased flow 79% compared with baseline (0.6±0.1 mL/min). Wall shear stress (WSS) increased or decreased accordingly, and remained elevated (9.2±2.0 dynes/cm²) in HF-AAA 14 days after PPE infusion. CD34⁺ cells were identified throughout the aortic wall in all flow conditions. Seven days after PPE infusion, HF-AAAs had more CD34⁺ cells than LF-AAA (187±10 versus 155±7 CD34⁺ cells/cross sectional, P<0.05), more medial smooth muscle cells, fewer infiltrative macrophages, and a smaller diameter than LF-AAA. LF-AAAs also contained more adventitial capillaries (CD34⁺ capillaries 181±12 versus 89±32/cross-sectional area in HF-AAA, P<0.05). The total progenitor cell/capillary index (CD34⁺ capillary plus CD31⁺ capillary/cross sectional area) was higher in LF-AAA (282±31 versus 129±47, P<0.05). Vascular endothelial (VEGF) and platelet-derived growth factor (PDGF) expression varied directly with capillary density between groups. Increased granulocyte-macrophage colony-stimulating factor (GM-CSF) expression was also present in LF-AAAs.

Conclusions— Hemodynamic conditions influence CD34⁺ cell localization and differentiation in experimental AAA. Adventitial capillary angiogenesis may augment inflammation and disease progression. Modulating cell lineage differentiation of mature progenitor cells may represent a novel therapeutic strategy to maintain medial cellularity and extracellular matrix integrity in AAA disease.

Vascular progenitor cells (CD34⁺ cells) localize within murine AAA, contributing to aneurysmal formation and progression. Luminal flow conditions regulate CD34⁺ cell differentiation and localization.

Key Words: blood flow • wall shear stress • vascular progenitor cell • angiogenesis • AAA • smooth muscle cells • macrophages

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