High-Resolution Quantitative Computed Tomography Demonstrating Selective Enhancement of Medium-Size Collaterals by Placental Growth Factor-1 in the Mouse Ischemic Hindlimb

Li, Weiming; Shen, Wen; Gill, Robert M.; Corbly, Angela K.; Jones, Bonita D.; Belagaje, Rama M.; Zhang, Yuke; Tang, Shaoqing; Chen, Yan; Zhai, Yan; Wang, Guo‐Ming; Wagle, Asavari; Hui, Kwan Y.; Westmore, Michael S.; Hanson, Jeffrey; Chen, Yunfei; Simons, Michael; Singh, Jai Pal

doi:10.1161/circulationaha.105.586818

Cited by 30 publications

(25 citation statements)

References 26 publications

(29 reference statements)

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“…This finding indicates that PlGF-induced vasculature is functional. It also agrees with the reported PlGF arteriogenic activity 11,32 and with the observation that PlGF knockout mice delayed wound healing associates with reduced number of "mature" cell-coated vessels. 4 The most striking effects exerted by PlGF gene expression are the increased formation and accelerated maturation of granulation tissue.…”

Section: Discussionsupporting

confidence: 92%

Placenta Growth Factor in Diabetic Wound Healing

Cianfarani

Zambruno

Brogelli

et al. 2006

The American Journal of Pathology

103

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Reduced microcirculation and diminished expression of growth factors contribute to wound healing impairment in diabetes. Placenta growth factor (PlGF), an angiogenic mediator promoting pathophysiological neovascularization, is expressed during cutaneous wound healing and improves wound closure by enhancing angiogenesis. By using streptozotocin-induced diabetic mice, we here demonstrate that PlGF induction is strongly reduced in diabetic wounds. Diabetic transgenic mice overexpressing PlGF in the skin displayed accelerated wound closure compared with diabetic wild-type littermates. Moreover, diabetic wound treatment with an adenovirus vector expressing the human PlGF gene (AdCMV.PlGF) significantly accelerated the healing process compared with wounds treated with a control vector. The analysis of treated wounds showed that PlGF gene transfer improved granulation tissue formation, maturation, and vascularization, as well as monocytes/macrophages local recruitment. Platelet-derived growth factor, fibroblast growth factor-2, and vascular endothelial growth factor mRNA levels were increased in AdCMV.PlGF-treated wounds , possibly enhancing PlGF-mediated effects. Finally , PlGF treatment stimulated cultured dermal fibroblast migration , pointing to a direct role of PlGF in accelerating granulation tissue maturation. In conclusion , our data indicate that reduced PlGF expression contributes to impaired wound healing in diabetes and that PlGF gene transfer to diabetic wounds exerts therapeutic activity by promoting different aspects of the repair process.

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Section: Discussionsupporting

confidence: 92%

Placenta Growth Factor in Diabetic Wound Healing

Cianfarani

Zambruno

Brogelli

et al. 2006

The American Journal of Pathology

103

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“…μCT studies were carried out as described previously (2,48). The ligated right hindlimb vasculature was scanned with a high-resolution μCT imaging system (GE eXplore Locus SP; GE Healthcare) set to an 8-μm effective detector pixel size.…”

Section: Study Approval All Animal Studies Were Approved By the Instmentioning

confidence: 99%

ERK1/2-Akt1 crosstalk regulates arteriogenesis in mice and zebrafish

Ren¹,

Deng²,

et al. 2010

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Arterial morphogenesis is an important and poorly understood process. In particular, the signaling events controlling arterial formation have not been established. We evaluated whether alterations in the balance between ERK1/2 and PI3K signaling pathways could stimulate arterial formation in the setting of defective arterial morphogenesis in mice and zebrafish. Increased ERK1/2 activity in mouse ECs with reduced VEGF responsiveness was achieved in vitro and in vivo by downregulating PI3K activity, suppressing Akt1 but not Akt2 expression, or introducing a constitutively active ERK1/2 construct. Such restoration of ERK1/2 activation was sufficient to restore impaired arterial development and branching morphogenesis in synectin-deficient mice and synectin-knockdown zebrafish. The same approach effectively stimulated arterial growth in adult mice, restoring arteriogenesis in mice lacking synectin and in atherosclerotic mice lacking both LDL-R and ApoB48. We therefore conclude that PI3K-ERK1/2 crosstalk plays a key role in the regulation of arterial growth and that the augmentation of ERK signaling via suppression of the PI3K signaling pathway can effectively stimulate arteriogenesis.

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“…1A. The gracilis collateral pathway has been previously described (15,16,32,33,44,56) and involves the gracilis artery, which originates from the profunda femoral (muscular branch) artery and passes through the superficial anterior and posterior gra- cilis muscles and reinserts into the distal saphenous artery. The deep adductor pathway originates as a branch of the internal iliac artery, passes along the ventral portion of the pelvis, and then penetrates the deeper adductor musculature to reinsert into the saphenous artery proximal to the reinsertion point of the gracilis collateral pathway.…”

Section: Identification Of Major Collateral Pathwaysmentioning

confidence: 99%

Suppressed hindlimb perfusion in Rac2^−/− and Nox2^−/− mice does not result from impaired collateral growth

Distasi

Case

Ziegler

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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arteriogenesis; hindlimb ischemia; necrosis; regeneration; NADPH oxidase 2 IN THE PERIPHERAL CIRCULATION, the dilation and enlargement of preexisting vessels that form collateral pathways subsequent to arterial occlusion are the primary vascular compensations that preserve tissue viability and maintain function. These vessels dilate within seconds (25,39,45,70) and undergo expansion for weeks (20,25,45,69). In various species, the preexisting vessels are the size of the smallest arteries, and they enlarge ϳ100% (14,20,35,45,56). Available clinical studies have indicated that subsequent to arterial occlusion in the peripheral circulation, the primary vessels that enlarge as collaterals are preexisting arteries (4,29,57). The largest of the preexisting vessels are typically those that become the dominant collaterals (35,45,51). Combined anatomic and modeling studies have predicted that hindlimb flow subsequent to femoral artery occlusion is primarily determined by these collaterals (22,56). This is consistent with studies of segmental resistances that demonstrated that compensation in the collateral vessels is of significantly greater hemodynamic importance than adaptations in the distal microvasculature (43,71,75). Nevertheless, few studies investigating the mechanisms of vascular compensation subsequent to arterial occlusion in mice have specifically identified and studied these preexisting vessels that form the primary collateral pathways. Such investigations are needed because angiogenesis and collateral growth are initiated by different stimuli, and differences exist in the molecules and mechanisms that mediate these important processes (7, 11).Leukocytes, especially lymphocytes (63, 74) and macrophages (2,33,37), have been shown to have an important role in vascular compensation to hindlimb ischemia. Recent studies by Tojo et al. (66) and Urao et al. (72) have established that NADPH oxidase 2 (Nox2)-derived ROS from bone marrowderived cells (BMDCs) have an important role in neovascularization in the ischemic mouse hindlimb. The initial report (66) concluded from microsphere data that collateral growth was impaired, but did not specifically identify collateral bypass vessels or measure their diameters.To investigate the hypothesis that Nox2-derived NAD(P)H oxidase mediates primary collateral growth subsequent to arterial occlusion, the present study used Rac2-null (Rac2 Ϫ/Ϫ ) and Nox2-null (Nox2 Ϫ/Ϫ ) mice and a novel method of identifying primary hindlimb collaterals. Rac2 is expressed primarily, if not exclusively, in hematopoietic cells (38, 52) and binds to and activates Nox2-containing NAD(P)H oxidase (24,40). In addition, leukocytes from Rac2 Ϫ/Ϫ and Nox2 Ϫ/Ϫ mice have impaired function related to reduced ROS production (47,66,72). We present a method to identify the dominant or primary collateral that should be the major collateral supplying flow to

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High-Resolution Quantitative Computed Tomography Demonstrating Selective Enhancement of Medium-Size Collaterals by Placental Growth Factor-1 in the Mouse Ischemic Hindlimb

Cited by 30 publications

References 26 publications

Placenta Growth Factor in Diabetic Wound Healing

Placenta Growth Factor in Diabetic Wound Healing

ERK1/2-Akt1 crosstalk regulates arteriogenesis in mice and zebrafish

Suppressed hindlimb perfusion in Rac2^−/− and Nox2^−/− mice does not result from impaired collateral growth

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High-Resolution Quantitative Computed Tomography Demonstrating Selective Enhancement of Medium-Size Collaterals by Placental Growth Factor-1 in the Mouse Ischemic Hindlimb

Cited by 30 publications

References 26 publications

Placenta Growth Factor in Diabetic Wound Healing

Placenta Growth Factor in Diabetic Wound Healing

ERK1/2-Akt1 crosstalk regulates arteriogenesis in mice and zebrafish

Suppressed hindlimb perfusion in Rac2−/− and Nox2−/− mice does not result from impaired collateral growth

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Suppressed hindlimb perfusion in Rac2^−/− and Nox2^−/− mice does not result from impaired collateral growth