About: Development of a two-stage limb ischemia model to better simulate human peripheral artery disease

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About: Development of a two-stage limb ischemia model to better simulate human peripheral artery disease Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Development of a two-stage limb ischemia model to better simulate human peripheral artery disease
Creator	Golledge, Jonathan Jose, Roby Krishna, Smriti Li, Jiaze Mohamed Omer, Safraz Morton, Susan
source	PMC
abstract	Peripheral arterial disease (PAD) develops due to the narrowing or blockage of arteries supplying blood to the lower limbs. Surgical and endovascular interventions are the main treatments for advanced PAD but alternative and adjunctive medical therapies are needed. Currently the main preclinical experimental model employed in PAD research is based on induction of acute hind limb ischemia (HLI) by a 1-stage procedure. Since there are concerns regarding the ability to translate findings from this animal model to patients, we aimed to develop a novel clinically relevant animal model of PAD. HLI was induced in male Apolipoprotein E (ApoE(−/−)) deficient mice by a 2-stage procedure of initial gradual femoral artery occlusion by ameroid constrictors for 14 days and subsequent excision of the femoral artery. This 2-stage HLI model was compared to the classical 1-stage HLI model and sham controls. Ischemia severity was assessed using Laser Doppler Perfusion Imaging (LDPI). Ambulatory ability was assessed using an open field test, a treadmill test and using established scoring scales. Molecular markers of angiogenesis and shear stress were assessed within gastrocnemius muscle tissue samples using quantitative polymerase chain reaction. HLI was more severe in mice receiving the 2-stage compared to the 1-stage ischemia induction procedure as assessed by LDPI (p = 0.014), and reflected in a higher ischemic score (p = 0.004) and lower average distance travelled on a treadmill test (p = 0.045). Mice undergoing the 2-stage HLI also had lower expression of angiogenesis markers (vascular endothelial growth factor, p = 0.004; vascular endothelial growth factor- receptor 2, p = 0.008) and shear stress response mechano-transducer transient receptor potential vanilloid 4 (p = 0.041) within gastrocnemius muscle samples, compared to animals having the 1-stage HLI procedure. Mice subjected to the 2-stage HLI receiving an exercise program showed significantly greater improvement in their ambulatory ability on a treadmill test than a sedentary control group. This study describes a novel model of HLI which leads to more severe and sustained ischemia than the conventionally used model. Exercise therapy, which has established efficacy in PAD patients, was also effective in this new model. This new model maybe useful in the evaluation of potential novel PAD therapies.
has issue date	2020-02-26(xsd:dateTime)
bibo:doi	10.1038/s41598-020-60352-4
bibo:pmid	32103073
has license	cc-by
sha1sum (hex)	4c2cd49bfcf2c38a171d98cb6688f633f52f4e79
schema:url	https://doi.org/10.1038/s41598-020-60352-4
resource representing a document's title	Development of a two-stage limb ischemia model to better simulate human peripheral artery disease
has PubMed Central identifier	PMC7044206
has PubMed identifier	32103073
schema:publication	Sci Rep
resource representing a document's body	covid:4c2cd49bfcf2c38a171d98cb6688f633f52f4e79#body_text
is schema:about of	named entity 'therapies' named entity 'develop' named entity 'score' named entity 'acute' named entity 'assessed' named entity 'open field test' named entity 'male' named entity 'test' named entity 'ability' named entity 'preclinical' named entity 'angiogenesis' named entity 'severe' named entity 'ABILITY TO' named entity 'EFFICACY' named entity 'VASCULAR ENDOTHELIAL GROWTH FACTOR' named entity 'ANIMAL MODEL' named entity 'MOLECULAR MARKERS' named entity 'TO TRANSLATE' named entity 'RECEPTOR' named entity 'ability' named entity 'subsequent' named entity 'growth factor' named entity 'animals' named entity 'sustained' named entity 'induced' named entity 'potential' named entity 'endovascular' named entity 'travelled' named entity 'model' named entity 'markers' named entity 'gastrocnemius muscle' named entity 'imaging' named entity 'shear stress' named entity 'based' named entity 'assessed' named entity 'average' named entity 'severe' named entity 'improvement' named entity 'gradual' named entity 'Doppler' named entity 'employed' named entity 'animal model' named entity 'vascular endothelial growth factor' named entity 'transient receptor potential' named entity 'pAD' named entity 'ApoE' named entity 'deficient mice' named entity 'Exercise therapy' named entity 'peripheral arterial disease' named entity 'pAD' named entity 'Mice' named entity 'gastrocnemius muscle' named entity 'open field test' named entity 'shear stress' named entity 'arteries' named entity 'quantitative polymerase chain reaction' named entity 'angiogenesis' named entity 'PAD' named entity 'shear stress' named entity 'ischemia' named entity 'femoral artery' named entity 'medical therapies' named entity 'control group' named entity 'Mice' named entity 'limb ischemia' named entity 'peripheral arterial disease' named entity 'evaluation' named entity 'gastrocnemius muscle' named entity 'lower limbs' named entity 'ischemic' named entity 'mice' named entity 'animal model' named entity 'peripheral artery disease' named entity 'ENDOTHELIAL GROWTH FACTOR' named entity 'MEDICAL THERAPIES' named entity 'ESTABLISHED'

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