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Skeletal muscle expression of adipose-specific phospholipase in peripheral artery disease

2020-10Journal article Restricted access
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dc.contributor.authorParmer, Caitlin
dc.contributor.authorDe Sousa-Coelho, Ana Luísa
dc.contributor.authorCheng, Henry S.
dc.contributor.authorDaher, Grace
dc.contributor.authorBurkart, Alison
dc.contributor.authorDreyfuss, Jonathan M.
dc.contributor.authorPan, Hui
dc.contributor.authorPrenner, Joshua C.
dc.contributor.authorKeilson, Jessica M.
dc.contributor.authorPande, Reena
dc.contributor.authorHenkin, Stanislav
dc.contributor.authorFeinberg, Mark W.
dc.contributor.authorPatti, Mary Elizabeth
dc.contributor.authorCreager, Mark A.
dc.date.accessioned2021-06-24T11:35:20Z
dc.date.available2021-06-24T11:35:20Z
dc.date.issued2020-10
dc.description.abstractFlow-limiting atherosclerotic lesions of arteries supplying the limbs are a cause of symptoms in patients with peripheral artery disease (PAD). Musculoskeletal metabolic factors also contribute to the pathophysiology of claudication, which is manifest as leg discomfort that impairs walking capacity. Accordingly, we conducted a case-control study to determine whether skeletal muscle metabolic gene expression is altered in PAD. Calf skeletal muscle gene expression of patients with PAD and healthy subjects was analyzed using microarrays. The top-ranking gene differentially expressed between PAD and controls (FDR < 0.001) wasPLA2G16, which encodes adipose-specific phospholipase A2 (AdPLA) and is implicated in the maintenance of insulin sensitivity and regulation of lipid metabolism. Differential expression was confirmed by qRT-PCR;PLA2G16was downregulated by 68% in patients with PAD (p< 0.001). Expression ofPla2g16was then measured in control (db/+) and diabetic (db/db) mice that underwent unilateral femoral artery ligation. There was significantly reduced expression ofPla2g16in the ischemic leg of both control and diabetic mice (by 51%), with significantly greater magnitude of reduction in the diabetic mice (by 79%). We conclude that AdPLA is downregulated in humans with PAD and in mice with hindlimb ischemia. Reduced AdPLA may contribute to impaired walking capacity in patients with PAD via its effects on skeletal muscle metabolism. Further studies are needed to fully characterize the role of AdPLA in PAD and to investigate its potential as a therapeutic target for alleviating symptoms of claudication.
dc.description.sponsorshipAmerican Diabetes AssociationAmerican Diabetes Association [K12HL083786]
dc.description.sponsorshipNational Heart, Lung, and Blood InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [K12HL083786]
dc.description.sponsorshipAmerican Heart AssociationAmerican Heart Association [10SDG4200060, 18SFRN33900085]
dc.description.sponsorshipJoslin Diabetes Research Center [P30 DK036836]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1177/1358863X20947467
dc.identifier.issn1358-863X
dc.identifier.urihttp://hdl.handle.net/10400.1/16412
dc.language.isoeng
dc.peerreviewedyes
dc.publisherSage
dc.subjectPeripheral artery disease (PAD)
dc.subjectIntermittent claudication
dc.subjectGene expression
dc.subjectGenetics
dc.subjectInsulin resistance
dc.subject.otherCardiovascular System & Cardiology
dc.titleSkeletal muscle expression of adipose-specific phospholipase in peripheral artery disease
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage410
oaire.citation.issue5
oaire.citation.startPage4011358863X20947467
oaire.citation.titleVascular Medicine
oaire.citation.volume25
person.familyNameDe Sousa-Coelho
person.givenNameAna Luísa
person.identifier.ciencia-id691B-A574-28ED
person.identifier.orcid0000-0002-8451-4302
rcaap.rightsrestrictedAccess
rcaap.typearticle
relation.isAuthorOfPublicationc7b0d14f-ae71-45a3-bce1-6dcd1fc66f67
relation.isAuthorOfPublication.latestForDiscoveryc7b0d14f-ae71-45a3-bce1-6dcd1fc66f67

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