| | |  | | | | Record from Web of Science® | | | | | | |
| TIME-COURSE OF INCREASED CELLULAR PROLIFERATION IN COLLATERAL ARTERIES AFTER ADMINISTRATION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR IN A RABBIT MODEL OF LOWER-LIMB VASCULAR INSUFFICIENCY |
|
|
| Author(s): TAKESHITA S, ROSSOW ST, KEARNEY M, ZHENG LP, BAUTERS C, BUNTING S, FERRARA N, SYMES JF, ISNER JM |
| Source: AMERICAN JOURNAL OF PATHOLOGY Volume: 147 Issue: 6 Pages: 1649-1660 Published: DEC 1995 |
| Times Cited: 94 References: 42 |
| Abstract: Proliferation of vascular cells has been previously shown to contribute to spontaneous development of coronary collaterals. Recent studies from several laboratories have established that collateral artery growth in both the heart and limb can be enhanced by administration of angiogenic growth factors, or therapeutic angiogenesis. In this study, we south (1) to define the extent and time course of endothelial cell (EC) and smooth muscle cell (SMC) proliferation accompanying spontaneous collateral development during limb ischemia and (2) to determine the extent to which proliferative activity of ECs and SMCs is augmented during therapeutic angiogenesis with vascular endothelial growth factor (VEGF), a heparin-binding EC-specific mitogen. Ten days after induction of limb ischemia by surgically excising the femoral artery of rabbits, either VEGF (500 to 1000 mu g) or saline was administered as a bolus into the iliac artery of the ischemic limb. Cellular proliferation was evaluated by bromodeoxyuridine labeling for 24 hours at day 0 (immediately before VEGF administration) and at days 3, 5, and 7 after VEGF. EC proliferation in the midzone collaterals of VEGF-treated animals increased 2.8-fold at day 5 (p < 0.05 versus control), and returned to baseline levels by day 7. SMC proliferation in midzone collaterals also increased 2.7-fold in response to VEGF (P < 0.05). No significant increase in EC or SMC proliferation was observed in either the stem or re-entry collaterals of VEGF-treated animals compared with untreated ischemic control animals. Reduction of hemodynamic deficit in the ischemic limb measured by lower limb blood pressure was documented at day 7 after VEGF (P < 0.01 versus untreated, ischemic control). These data thus (1) establish the contribution of cellular proliferation to collateral vessel development in limb ischemia and (2) support the concept that augmented cellular proliferation concept that augmented cellular proliferation contributes to the enhanced formation of collateral vessels after therapeutic angiogenesis with VEGF. |
| Document Type: Article |
| Language: English |
Addresses:
1. TUFTS UNIV, SCH MED, ST ELIZABETH MED CTR, DEPT MED CARDIOL, BOSTON, MA 02135 USA
2. TUFTS UNIV, SCH MED, ST ELIZABETH MED CTR, DEPT CARDIOTHORAC SURG, BOSTON, MA 02135 USA
3. TUFTS UNIV, SCH MED, ST ELIZABETH MED CTR, DEPT BIOL RES, BOSTON, MA 02135 USA
4. GENENTECH INC, DEPT CARDIOVASC RES, S SAN FRANCISCO, CA 94080 USA |
| Publisher: AMER SOC INVESTIGATIVE PATHOLOGY, INC, 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 |
| Subject Category: Pathology |
| IDS Number: TJ665 |
| ISSN: 0002-9440 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |