Revascularization in the rabbit hindlimb: dissociation between capillary sprouting and arteriogenesis

Hershey, James C.; Baskin, Elizabeth; Glass, Joan D.; Hartman, Halea A.; Gilberto, David B.; Rogers, Irene; Cook, Jacquelynn J.

doi:10.1016/s0008-6363(00)00232-7

Cited by 166 publications

(179 citation statements)

References 32 publications

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“…Using our method in a rat model of acute femoral artery occlusion, we observed neovascularization and subsequent recovery of perfusion via collaterals, consistent with previous reports [7,8]. Interestingly, in the preparations made early after induction of ischemia (directly postoperatively and at Day 7), a thrombus was present in the part of the ligated femoral artery distal to the site of occlusion.…”

Section: Discussionsupporting

confidence: 89%

A study of neovascularization in the rat ischemic hindlimb using Araldite casting and Spalteholtz tissue clearing

Westerweel

Rookmaaker

Zonneveld

et al. 2005

Cardiovascular Pathology

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Introduction: Understanding neovascularization is an important prerequisite for therapeutic advances aimed at the salvation of ischemic tissues. We explored an alternative strategy to corrosion casting for visualizing neovascularization in a rat hindlimb ischemia model. Methods: Rats were subjected to hindlimb ischemia by femoral artery ligation. Directly after femoral artery occlusion and at 7, 14, 21 and 28 days postsurgery, rats were sacrificed, and neovascularization was evaluated by vascular casting with Araldite plastic and subsequent Spalteholtz tissue clearing. Results: Semitransparent preparations were obtained, in which the casted arteries could be directly and three-dimensionally visualized in detail and in relation to the surrounding tissue. In the vascular casts, collateral formation and recanalization of previously thrombosed arteries were demonstrated. Conclusions: We describe an alternative approach to study neovascularization in animal models. This method, which combines Araldite plastic vascular casting with Spalteholtz tissue clearing, preserves all vasculature as well as the surrounding tissue. In a small time series in rat ischemic hindlimbs, we show that restoration of blood flow after ischemia not only involves newly formed collaterals, but also recanalization of previously thrombosed arterial segments. D

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Section: Discussionsupporting

confidence: 89%

A study of neovascularization in the rat ischemic hindlimb using Araldite casting and Spalteholtz tissue clearing

Westerweel

Rookmaaker

Zonneveld

et al. 2005

Cardiovascular Pathology

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“…For example, it has been shown that the inclusion of BSA facilitates the release of growth factor from a polymer matrix (25). By carefully choosing these parameters, the release profile can be finely controlled, which may be especially important for optimizing the delivery of angiogenic factors (26,27). It has been demonstrated that in vivo release rates can be approximately twice the rates observed in vitro (24).…”

Section: Discussionmentioning

confidence: 99%

In vitro release of vascular endothelial growth factor from gadolinium‐doped biodegradable microspheres

Faranesh

Nastley

Cruz

et al. 2004

Magnetic Resonance in Med

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A drug delivery vehicle was constructed that could be visualized noninvasively with MRI. The biodegradable polymer poly(DL-lactic-co-glycolic acid) (PLGA) was used to fabricate microspheres containing vascular endothelial growth factor (VEGF) and the MRI contrast agent gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). The microspheres were characterized in terms of size, drug and contrast agent encapsulation, and degradation rate. The PLGA microspheres had a mean diameter of 48 ؎ 18 m. The gadolinium loading was 17 ؎ 3 g/mg polymer and the VEGF loading was 163 ؎ 22 ng/mg polymer. Electron microscopy revealed that the Gd was dispersed throughout the microspheres and it was confirmed that the Gd loading was sufficient to visualize the microspheres under MRI. VEGF and Gd-DTPA were released from the microspheres in vitro over a period of ϳ6 weeks in three phases: a burst, followed by a slow steady-state, then a rapid steady-state. Biodegradable Gd-doped microspheres can be effectively used to deliver drugs in a sustained manner, while being monitored noninvasively with MRI.

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“…Capillary sprouting does not translate into improved flow, which depends on the growth of larger collateral vessels. 1 TNF-␣ has been localized to the macrophages of growing collateral arteries. 2 Using reverse transcriptase-polymerase chain reaction, we find TNF-␣ mRNA in the region of collateral artery growth 2 days after femoral artery occlusion in the mouse (C. Keith Ozaki, unpublished data, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…1 Perivascular inflammation and monocyte/macrophage accumulation accompany this process. 2 Tumor necrosis factor-␣ (TNF-␣) is an important proximal mediator of inflammation.…”

mentioning

confidence: 99%

Direct Evidence for Tumor Necrosis Factor-α Signaling in Arteriogenesis

et al. 2002

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Background-Arteriogenesis serves as an efficient mechanism for flow restoration after arterial occlusion. This process is associated with inflammatory mediators such as tumor necrosis factor-␣ (TNF-␣), although their role in arteriogenesis remains unclear. We hypothesized that arteriogenesis is reduced in mice lacking functional TNF-␣ or p55 receptor. To test this hypothesis, we developed a novel microsphere-based murine model of hindlimb perfusion measurement. Methods and Results-Unilateral femoral arteries of nude (nϭ9), TNF-␣ Ϫ/Ϫ (nϭ9), TNF-␣ receptor p55 Ϫ/Ϫ (nϭ8), and p75 Ϫ/Ϫ (nϭ8) mice as well as their appropriate genetic background controls were occluded. The nude mice underwent laser Doppler hindlimb flux measurements preoperatively, postoperatively, and after 7 days. Seven days after ligation, all animals underwent tissue perfusion determinations using fluorescent microspheres. Laser Doppler findings confirmed acute decrease in flux with falsely normal values after 1 week. Microsphere results from control mice showed perfusion restoration to values Ϸ50% of normal within 7 days. Key Words: collateral circulation Ⅲ inflammation Ⅲ microspheres Ⅲ blood flow Ⅲ remodeling A rteriogenesis (remodeling of preexistent arteriolar collateral networks into large collateral conductance arteries) serves as the most efficient mechanism to restore flow after arterial occlusion. 1 Perivascular inflammation and monocyte/macrophage accumulation accompany this process. 2 Tumor necrosis factor-␣ (TNF-␣) is an important proximal mediator of inflammation. Most prototypical inflammatory TNF-␣ signaling occurs by TNF-␣ binding to its p55 receptor. 3 Previous studies have associated TNF-␣ with arteriogenesis. 2 We hypothesized that arteriogenesis proceeds by way of TNF-␣ signaling via the p55 receptor. Specifically, we hypothesized that arteriogenesis is reduced in mice lacking functional TNF-␣ or p55 receptor. We developed and validated a novel model of perfusion measurement in the mouse hindlimb to test this hypothesis. Methods Animal ModelThis study conforms to the Guide for the Care and Use of Laboratory Animals (NIH publication No. 85-23, revised 1996). Nine athymic nude, 8 TNF-␣ receptor p55Ϫ/Ϫ3,4 (N5 backcross onto C57BL/6J, maintained by brother/sister matings) and 9 TNF-␣ Ϫ/Ϫ5(on B6x129 F1 background, maintained by sister/brother matings) (both provided by Dr Carl K. Edwards III, Amgen, Inc, Thousand Oaks, Calif), 8 TNF-␣ receptor p75 Ϫ/Ϫ , 7 B6x129, and 9 C57BL/6J (Jackson Laboratory, Bar Harbor, Maine) mice underwent unilateral femoral artery ligation. The right femoral artery was ligated immediately distal to the inguinal ligament. Because collateral arteries develop from preexisting arteriolar connections spanning from the profunda femoris and circumflexa femoris to the genualis and saphena parva arteries, 4 the femoral artery was not excised to leave these vessels intact. In rabbits, this technique does not lead to ischemia in the region of collateral artery growth or distal to the site of ligation. 5 Wounds were cl...

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Revascularization in the rabbit hindlimb: dissociation between capillary sprouting and arteriogenesis

Cited by 166 publications

References 32 publications

A study of neovascularization in the rat ischemic hindlimb using Araldite casting and Spalteholtz tissue clearing

A study of neovascularization in the rat ischemic hindlimb using Araldite casting and Spalteholtz tissue clearing

In vitro release of vascular endothelial growth factor from gadolinium‐doped biodegradable microspheres

Direct Evidence for Tumor Necrosis Factor-α Signaling in Arteriogenesis

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