scholarly journals The Lipopeptide MALP-2 Promotes Collateral Growth

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 997
Author(s):  
Kerstin Troidl ◽  
Christian Schubert ◽  
Ann-Kathrin Vlacil ◽  
Ramesh Chennupati ◽  
Sören Koch ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Femoral Artery ◽  
Hind Limb ◽  
Immune Defense ◽  
Laser Speckle ◽  
Mesenteric Arteries ◽  
Endothelial Cell Proliferation ◽  
Collateral Arteries ◽  
Collateral Growth

Beyond their role in pathogen recognition and the initiation of immune defense, Toll-like receptors (TLRs) are known to be involved in various vascular processes in health and disease. We investigated the potential of the lipopeptide and TLR2/6 ligand macrophage activating protein of 2-kDA (MALP-2) to promote blood flow recovery in mice. Hypercholesterolemic apolipoprotein E (Apoe)-deficient mice were subjected to microsurgical ligation of the femoral artery. MALP-2 significantly improved blood flow recovery at early time points (three and seven days), as assessed by repeated laser speckle imaging, and increased the growth of pre-existing collateral arteries in the upper hind limb, along with intimal endothelial cell proliferation in the collateral wall and pericollateral macrophage accumulation. In addition, MALP-2 increased capillary density in the lower hind limb. MALP-2 enhanced endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) release from endothelial cells and improved the experimental vasorelaxation of mesenteric arteries ex vivo. In vitro, MALP-2 led to the up-regulated expression of major endothelial adhesion molecules as well as their leukocyte integrin receptors and consequently enhanced the endothelial adhesion of leukocytes. Using the experimental approach of femoral artery ligation (FAL), we achieved promising results with MALP-2 to promote peripheral blood flow recovery by collateral artery growth.

scholarly journals Temporal patterns of blood flow and nitric oxide synthase expression affect macrophage accumulation and proliferation during collateral growth

2010 ◽  
Vol 2 (1) ◽  
pp. 18 ◽  
Author(s):  
Hendrik B Sager ◽  
Ralf Middendorff ◽  
Kim Rauche ◽  
Joachim Weil ◽  
Wolfgang Lieb ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Temporal Patterns ◽  
Collateral Growth ◽  
Oxide Synthase ◽  
Macrophage Accumulation

scholarly journals IL10 Alters Peri-Collateral Macrophage Polarization and Hind-Limb Reperfusion in Mice after Femoral Artery Ligation

2020 ◽  
Vol 21 (8) ◽  
pp. 2821 ◽  
Author(s):  
Alexander M. Götze ◽  
Christian Schubert ◽  
Georg Jung ◽  
Oliver Dörr ◽  
Christoph Liebetrau ◽  
...  
Keyword(s):  
Femoral Artery ◽  
Hind Limb ◽  
Macrophage Activation ◽  
Macrophage Polarization ◽  
Doppler Imaging ◽  
Activated Macrophages ◽  
Artery Ligation ◽  
Alternatively Activated Macrophages ◽  
Collateral Growth ◽  
Alternatively Activated

Arteriogenesis is a process by which a pre-existing arterioarterial anastomosis develops into a functional collateral network following an arterial occlusion. Alternatively activated macrophages polarized by IL10 have been described to promote collateral growth. This study investigates the effect of different levels of IL10 on hind-limb reperfusion and the distribution of perivascular macrophage activation types in mice after femoral artery ligation (FAL). IL10 and anti-IL10 were administered before FAL and the arteriogenic response was measured by Laser-Doppler-Imaging perioperatively, after 3, 7, and 14 d. Reperfusion recovery was accelerated when treated with IL10 and impaired with anti-IL10. Furthermore, symptoms of ischemia on ligated hind-limbs had the highest incidence after application of anti-IL10. Perivascular macrophages were immunohistologically phenotyped using CD163 and CD68 in adductor muscle segments. The proportion of alternatively activated macrophages (CD163+/CD68+) in relation to classically activated macrophages (CD163−/CD68+) observed was the highest when treated with IL10 and suppressed with anti-IL10. This study underlines the proarteriogenic response with increased levels of IL10 and demonstrates an in-vivo alteration of macrophage activation types in the perivascular bed of growing collaterals.

scholarly journals Requirement of β1 integrin for endothelium-dependent vasodilation and collateral formation in hindlimb ischemia

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Carina Henning ◽  
Anna Branopolski ◽  
Dominik Schuler ◽  
Dimitrios Dimitroulis ◽  
Patrik Huelsemann ◽  
...  
Keyword(s):  
Blood Flow ◽  
Endothelial Cell ◽  
Femoral Artery ◽  
Β1 Integrin ◽  
Hindlimb Ischemia ◽  
High Frequency Ultrasound ◽  
Blocking Antibody ◽  
Arterial Lumen ◽  
Collateral Arteries ◽  
Acute Increase

AbstractAn acute increase in blood flow triggers flow-mediated dilation (FMD), which is mainly mediated by endothelial nitric oxide synthase (eNOS). A long-term increase in blood flow chronically enlarges the arterial lumen, a process called arteriogenesis. In several common human diseases, these processes are disrupted for as yet unknown reasons. Here, we asked whether β1 integrin, a mechanosensory protein in endothelial cells, is required for FMD and arteriogenesis in the ischemic hindlimb. Permanent ligation of the femoral artery in C57BL/6 J mice enlarged pre-existing collateral arteries and increased numbers of arterioles in the thigh. In the lower leg, the numbers of capillaries increased. Notably, injection of β1 integrin-blocking antibody or tamoxifen-induced endothelial cell-specific deletion of the gene for β1 integrin (Itgb1) inhibited both arteriogenesis and angiogenesis. Using high frequency ultrasound, we demonstrated that β1 integrin-blocking antibody or endothelial cell-specific depletion of β1 integrin attenuated FMD of the femoral artery, and blocking of β1 integrin function did not further decrease FMD in eNOS-deficient mice. Our data suggest that endothelial β1 integrin is required for both acute and chronic widening of the arterial lumen in response to hindlimb ischemia, potentially via functional interaction with eNOS.

scholarly journals Overexpression of endothelial nitric oxide synthase increases skeletal muscle blood flow and oxygenation in severe rat hind limb ischemia

2003 ◽  
Vol 38 (4) ◽  
pp. 820-826 ◽  
Author(s):  
Lucy S Brevetti ◽  
David S Chang ◽  
Gale L Tang ◽  
Rajabrata Sarkar ◽  
Louis M Messina
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Endothelial Nitric Oxide Synthase ◽  
Hind Limb ◽  
Muscle Blood Flow ◽  
Limb Ischemia ◽  
Skeletal Muscle Blood Flow ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Angiogenesis but not collateral growth is associated with ischemia after femoral artery occlusion

1997 ◽  
Vol 273 (3) ◽  
pp. H1255-H1265 ◽  
Author(s):  
W. D. Ito ◽  
M. Arras ◽  
D. Scholz ◽  
B. Winkler ◽  
P. Htun ◽  
...  
Keyword(s):  
Femoral Artery ◽  
Molecular Mechanisms ◽  
Artery Occlusion ◽  
Sprouting Angiogenesis ◽  
Collateral Arteries ◽  
Femoral Artery Occlusion ◽  
Adductor Muscles ◽  
Collateral Growth ◽  
Collateral Artery ◽  
Vascular Proliferation

It remains unclear whether capillary sprouting (angiogenesis) and in situ growth of muscular collateral arteries share the same or different molecular mechanisms. To study the role of ischemia in these two forms of vascular proliferation, we measured tissue flows and maximum collateral conductances in hindlimbs of 22 rabbits previously subjected to either acute, 7-day, 21-day, or no femoral artery occlusion. After 1 wk of femoral artery occlusion, corkscrew collaterals were observed radiographically in the thigh. These collaterals showed histochemical evidence for active proliferation of endothelial and smooth muscle cells. Maximum collateral conductance increased sixfold in the 1st wk. Perfusion deficits, however, were only observed in the distal adductor muscles (region of collateral reentry). In the lower leg, which suffered from a profound perfusion deficit, conductance increased in the absence of any visible collateral arteries but with evidence for capillary proliferation. This study therefore demonstrates that upon femoral artery occlusion angiogenesis occurs in regions of profound ischemia, whereas no direct correlation can be drawn between ischemia and collateral artery development.

Abstract 321: Prasugrel, a Platelet P2y 12 Receptor Antagonist, Improves Abnormal Gait in a Novel Murine Model of Thrombotic Hind Limb Ischaemia

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Kousaku Ohno ◽  
Atsuyuki Tomizawa ◽  
Makoto Mizuno ◽  
Joseph A Jakubowski ◽  
Atsuhiro Sugidachi
Keyword(s):  
Blood Flow ◽  
Femoral Artery ◽  
Murine Model ◽  
Hind Limb ◽  
Limb Ischaemia ◽  
Phase Duration ◽  
Flow Reduction ◽  
Blood Flow Reduction ◽  
Gait Abnormalities ◽  
Deficient Mice

Background: The efficacy of P2Y 12 inhibition for the prevention of cardiovascular events in patients with peripheral arterial disease (PAD) has been established. However the therapeutic effects on ischaemic limb manifestations are less clear. Accordingly, we developed a novel murine model of thrombotic hind limb ischaemia to reflect that found in patients with PAD exhibiting ischaemic limb symptoms. We further investigated the effects of P2Y 12 inhibition by prasugrel in this model. Methods and Results: Thrombus formation induced by application of ferric chloride to the femoral artery resulted in a significant reduction in blood flow in the injured limb. In gait analysis of the ischaemic limb using the CatWalk system, maximum contact area and stance phase duration were reduced and swing phase duration increased in this model. Blood flow reduction and gait abnormalities gradually recovered over 21 days to levels present before arterial injury. Compared to wild-type (WT) mice, significant increases in blood flow and improvement in gait were observed in P2Y 12 -deficient mice. In addition, daily oral administration of prasugrel (3 mg/kg/day) to WT mice resulted in significant inhibition of blood flow reduction and gait abnormalities to levels found in P2Y 12 deficient mice. Conclusions: In conclusion, acute femoral artery thrombosis resulted in hind limb ischaemia and moderate gait abnormalities in mice. In addition, the present study suggests a therapeutic role for P2Y 12 antagonism in reducing the manifestations of limb ischaemia in PAD.

scholarly journals Endothelial nitric oxide synthase affects both early and late collateral arterial adaptation and blood flow recovery after induction of hind limb ischemia in mice

2010 ◽  
Vol 51 (1) ◽  
pp. 165-173 ◽  
Author(s):  
Brian Park ◽  
Ari Hoffman ◽  
Yagai Yang ◽  
Jinglian Yan ◽  
Guodong Tie ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Hind Limb ◽  
Limb Ischemia ◽  
Hind Limb Ischemia ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Collateral arteries grow from preexisting anastomoses in the rat hindlimb

2002 ◽  
Vol 283 (5) ◽  
pp. H2012-H2020 ◽  
Author(s):  
Sandra Herzog ◽  
Hendrik Sager ◽  
Eugen Khmelevski ◽  
Andrea Deylig ◽  
Wulf D. Ito
Keyword(s):  
Femoral Artery ◽  
Artery Occlusion ◽  
Separate Entity ◽  
Vascular Casts ◽  
Collateral Arteries ◽  
Femoral Artery Occlusion ◽  
Collateral Growth ◽  
Vascular Proliferation ◽  
Collateral Vessels ◽  
Biphasic Process

Previous findings have suggested that collateral arteries grow from preexisting arteriolar anastomoses (“arteriogenesis”). To investigate whether collateral growth occurs without preceding angiogenesis, we obtained vascular casts and postmortem angiographies 3, 7, and 21 days after unilateral femoral artery occlusion in the rat. Proliferation kinetics were determined after 5′-bromo-2′-desoxyuridin infusion. A preexisting anastomosis was identified. Proliferation of this vessel began 24 h after femoral artery occlusion, increased maximally during the first 3 days, and reached 60% at day 7. Cell division was restricted to preexisting anastomoses and occurred neither in directly neighboring arterial vessels nor in capillaries. Collateral vessels doubled their diameter within 7 days and assumed a typical corkscrew appearance (increase of length: 21%). After 7 days of occlusion, we measured a further increase of length (14%) but no proliferation or increase of diameter. We conclude that arteriogenesis is a biphasic process involving rapid proliferation of preexisting arteriolar shunts followed by pronounced remodeling processes. Arteriogenesis occurs independently of angiogenesis and denotes a separate entity of vascular proliferation.

Comparison of femoral artery, femoral vein, and total hind limb blood flow in dogs

1967 ◽  
Vol 114 (5) ◽  
pp. 653-657 ◽  
Author(s):  
Robert D. Wuerflein ◽  
Robert H. Smiley ◽  
Gilbert S. Campbell
Keyword(s):  
Blood Flow ◽  
Femoral Artery ◽  
Hind Limb ◽  
Femoral Vein ◽  
Limb Blood Flow

scholarly journals Assessment of mouse hind limb endothelial function by measuring femoral artery blood flow responses

2011 ◽  
Vol 53 (5) ◽  
pp. 1350-1358 ◽  
Author(s):  
Chao-Hung Wang ◽  
Kuo-Ti Chen ◽  
Hsiu-Fu Mei ◽  
Ju-Fang Lee ◽  
Wen-Jin Cherng ◽  
...  
Keyword(s):  
Blood Flow ◽  
Endothelial Function ◽  
Femoral Artery ◽  
Hind Limb ◽  
Artery Blood Flow ◽  
Femoral Artery Blood Flow
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