Differential Arterial/Venous Expression of NG2 Proteoglycan in Perivascular Cells Along Microvessels: Identifying a Venule‐Specific Phenotype

Murfee, Walter L.; Skalak, Thomas C.; Peirce, Shayn M.

doi:10.1080/10739680590904955

Cited by 123 publications

(128 citation statements)

References 33 publications

(55 reference statements)

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“…In quiescent rat mesenteric tissues NG2 labeling identifies smooth muscle cells along arterioles and vascular pericytes along all capillary vessels, yet not by smooth muscle cells along venules (Murfee et al, 2005). Our observations in typical SHR mesenteric networks indicate that a subset of capillaries are covered by NG2-positive pericytes and that pre-and post-capillary vessels positive for SM α-actin expression (data not shown) lack NG2 arterial/venous identification.…”

Section: Role For Perivascular Cells In Hypertensionmentioning

confidence: 62%

“…In the SHR networks NG2-positive labeling is present only on a subset of capillaries ( Figure 2A). Pericyte specific NG2-positive cell labeling along capillaries was confirmed by identification of the characteristic elongated, wrapping morphology ( Figure 3; Murfee et al, 2005). These NG2 labeling patterns seemed to be associated with the SHR and WKY architectural differences.…”

Section: Resultsmentioning

confidence: 83%

“…Capillaries were identified based on either vessel diameter (<10 μm) or blind-ended location. Pericyte specific NG2 positive cell labeling along capillaries was confirmed by identification of the typical elongated pericyte morphology (Murfee et al, 2005). Finally, for the evaluation of lymphatic vessels in the SHR and WKY tissues, additional mesenteric sectors were harvested from adult Wistar rats and immunolabeled for PECAM following the protocol as described above.…”

Section: Microvascular Network Evaluation and Image Acquisitionmentioning

confidence: 99%

“…Similar to methods previously described (Murfee et al, 2007;Murfee et al, 2005), tissue specimens were labeled with one of the following immunolabeling protocols using primary antibodies against: A) platelet endothelial adhesion molecule (PECAM; CD31); or B) PECAM + neuron-glia antigen 2 (NG2). For the PECAM group 2 tissues were labeled per animal.…”

Section: In-situ Immunohistochemistrymentioning

confidence: 99%

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Chapter 12 Structure of Microvascular Networks in Genetic Hypertension

Murfee

Schmid‐Schönbein

2008

Methods in Enzymology

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Microvascular rarefaction, defined by a loss of terminal arterioles, small venules and/or capillaries, is a common characteristic of the hypertension syndrome. While rarefaction has been associated with vessel specific free radical production, deficient leukocyte adhesion, and cellular apoptosis, the relationships of rarefaction with structural alterations at the network and cellular level remain largely unexplored. The objective of this study was to examine the architecture and perivascular cell phenotypes along microvascular networks in hypertensive versus normotensive controls in the context of imbalanced angiogenesis. Mesenteric tissues from age-matched adult male spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were harvested and immnolabeled for PECAM and neuron-glia antigen 2 (NG2). Evaluation of intact rat mesenteric microvascular networks rats suggests that network alterations associated with hypertension are more complex than just a loss of vessels. Typical SHR versus WKY networks demonstrate a reduced branching architecture marked by more proximal arteriole/venous anastomoses and an absence of NG2 labeling along arterioles. Although less frequent, larger SHR microvascular networks display regions of dramatically increased vascular density. SHR and WKY lymphatic networks demonstrate increased vessel diameters and vascular density compared to networks in normotensive Wistar rats (the strain from which both the SHR and WKY originated). These observations provide a rationale for investigating the presence of local angiogenic factors and response of microvascular networks to therapies aimed at reversing rarefaction in genetic hypertension.

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Section: Role For Perivascular Cells In Hypertensionmentioning

confidence: 62%

Section: Resultsmentioning

confidence: 83%

Section: Microvascular Network Evaluation and Image Acquisitionmentioning

confidence: 99%

Section: In-situ Immunohistochemistrymentioning

confidence: 99%

See 2 more Smart Citations

Chapter 12 Structure of Microvascular Networks in Genetic Hypertension

Murfee

Schmid‐Schönbein

2008

Methods in Enzymology

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“…Tissue samples immunostained for neuron-glial antigen 2 (NG2), a proteoglycan expressed in arterioles and not venules, were processed as described above for CD31 (17). The rabbit polyclonal anti-NG2 (Millipore, Billerica, MA) was diluted to 1:200 in PBS with 1% BSA.…”

Section: Methodsmentioning

confidence: 99%

Mesenchymal stem cells contribute to vascular growth in skeletal muscle in response to eccentric exercise

Huntsman

Zachwieja

Zou

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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-The ␣ 7␤1-integrin is an adhesion molecule highly expressed in skeletal muscle that can enhance regeneration in response to eccentric exercise. We have demonstrated that mesenchymal stem cells (MSCs), predominantly pericytes, accumulate in muscle (mMSCs) overexpressing the ␣ 7B-integrin (MCK:␣7B; ␣7Tg) and contribute to new fiber formation following exercise. Since vascularization is a common event that supports tissue remodeling, we hypothesized that the ␣ 7-integrin and/or mMSCs may stimulate vessel growth following eccentric exercise. Wild-type (WT) and ␣ 7Tg mice were subjected to single or multiple (3 times/wk, 4 wk) bouts of downhill running exercise. Additionally, 1,1=-dioctadecyl-3,3,3=,3=-tetramethylindocarbocyanine perchlorate (DiI) -labeled mMSCs were intramuscularly injected into WT recipients. A subset of recipient mice were run downhill before injection to recapitulate the exercised microenvironment. While total number of CD31 ϩ vessels declined in both WT and ␣7Tg muscle following a single bout of exercise, the number of larger CD31 ϩ vessels with a visible lumen was preferentially increased in ␣7Tg mice following eccentric exercise training (P Ͻ 0.05). mMSC transplantation similarly increased vessel diameter and the total number of neuron-glial antigen-2 (NG2 ϩ ) arterioles postexercise. Secretion of arteriogenic factors from mMSCs in response to mechanical strain, including epidermal growth factor and granulocyte macrophage-colony stimulating factor, may account for vessel remodeling. In conclusion, this study demonstrates that the ␣ 7-integrin and mMSCs contribute to increased vessel diameter size and arteriolar density in muscle in response to eccentric exercise. The information in this study has implications for the therapeutic treatment of injured muscle and disorders that result in vessel occlusion, including peripheral artery disease.integrin; pericyte; remodeling; angiogenesis; arteriole INTEGRINS ARE TRANSMEMBRANE adhesion proteins comprised of noncovalently bound ␣-and ␤-subunits. Integrins form clusters and recruit cytoskeletal and cytoplasmic proteins to the cell membrane to provide a mechanism of communication between the outside and inside of the cell (10). In skeletal muscle, the ␣ 7 ␤ 1 -integrin is the predominant heterodimer based on high levels of protein expression, and its primary function is to ensure adhesion by providing a stabilizing link between the actin cytoskeleton and the external environment, specifically, laminin (6). Transgenic expression of the integrin in mouse muscle can suppress macrophage infiltration, sarcolemmal damage, and reductions in force following eccentric exercise (3, 4, 13). Our recently published work also suggests ␣ 7BX2 -integrin overexpression (MCK:␣ 7BX2 ; ␣ 7 Tg) can increase myogenesis, hypertrophic signaling, myofibrillar content, fiber cross-sectional area, muscle cross-sectional area, and maximal isometric force following single or multiple bouts of eccentric exercise (13, 34), a type of exercise that results in muscle lengthening during...

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Selective Endothelial Hyperactivation of Oncogenic KRAS Induces Brain Arteriovenous Malformations in Mice

Park

Kim

Huang³

et al. 2021

Annals of Neurology

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Objective: Brain arteriovenous malformations (bAVMs) are a leading cause of hemorrhagic stroke and neurological deficits in children and young adults, however, no pharmacological intervention is available to treat these patients. Although more than 95% of bAVMs are sporadic without family history, the pathogenesis of sporadic bAVMs is largely unknown, which may account for the lack of therapeutic options. KRAS mutations are frequently observed in cancer, and a recent unprecedented finding of these mutations in human sporadic bAVMs offers a new direction in the bAVM research. Using a novel adeno-associated virus targeting brain endothelium (AAV-BR1), the current study tested if endothelial KRAS G12V mutation induces sporadic bAVMs in mice. Methods: Five-week-old mice were systemically injected with either AAV-BR1-GFP or -KRAS G12V . At 8 weeks after the AAV injection, bAVM formation and characteristics were addressed by histological and molecular analyses. The effect of MEK/ERK inhibition on KRAS G12V -induced bAVMs was determined by treatment of trametinib, a US Food and Drug Administration (FDA)-approved MEK/ERK inhibitor. Results: The viral-mediated KRAS G12V overexpression induced bAVMs, which were composed of a tangled nidus mirroring the distinctive morphology of human bAVMs. The bAVMs were accompanied by focal angiogenesis, intracerebral hemorrhages, altered vascular constituents, neuroinflammation, and impaired sensory/cognitive/motor functions. Finally, we confirmed that bAVM growth was inhibited by trametinib treatment. Interpretation: Our innovative approach using AAV-BR1 confirms that KRAS mutations promote bAVM development via the MEK/ERK pathway, and provides a novel preclinical mouse model of bAVMs which will be useful to develop a therapeutic strategy for patients with bAVM.

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Differential Arterial/Venous Expression of NG2 Proteoglycan in Perivascular Cells Along Microvessels: Identifying a Venule‐Specific Phenotype

Cited by 123 publications

References 33 publications

Chapter 12 Structure of Microvascular Networks in Genetic Hypertension

Chapter 12 Structure of Microvascular Networks in Genetic Hypertension

Mesenchymal stem cells contribute to vascular growth in skeletal muscle in response to eccentric exercise

Selective Endothelial Hyperactivation of Oncogenic KRAS Induces Brain Arteriovenous Malformations in Mice

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