Inflammation Is a Histological Characteristic of Skeletal Muscle in Chronic Limb Threatening Ischemia

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorFERREIRA, Joana
dc.contributor.authorAFONSO, Julieta
dc.contributor.authorLONGATTO-FILHO, Adhemar
dc.contributor.authorROQUE, Susana
dc.contributor.authorCARNEIRO, Alexandre
dc.contributor.authorVILE, Isabel
dc.contributor.authorSILVA, Cristina
dc.contributor.authorCUNHA, Cristina
dc.contributor.authorMESQUITA, Amilcar
dc.contributor.authorCOTTER, Jorge
dc.contributor.authorCORREIA-NEVES, Margarida
dc.contributor.authorMANSILHA, Armando
dc.contributor.authorCUNHA, Pedro
dc.date.accessioned2024-04-05T19:36:26Z
dc.date.available2024-04-05T19:36:26Z
dc.date.issued2024
dc.description.abstractBackground: The loss of skeletal muscle is a prognostic factor in several diseases including in patients with chronic limb threatening ischemia (CLTI). Patients with CLTI also have a lower skeletal mass and area when compared to those with claudication. However, there are no currently available data regarding the histological characteristics of core muscles in patients with CLTI. This study aims to determine the differences in core skeletal muscles between patients with claudication and those with CLTI. The second aim is to evaluate the differences in myokines, which are molecules secreted by skeletal muscle, between patients with claudication and those with CLTI. Methods: An observational, prospective study was conducted from January 2018 to July 2022 involving consecutive patients with peripheral arterial disease (PAD). The clinical characteristics were registered. In PAD patients with surgical indication for common femoral artery approach, samples of sartorius skeletal muscle (and not from the limb muscles directly involved in the ischemic process) were collected. The samples were submitted to histological characterization on hematoxylin-eosin and to immunohistochemical analysis to detect CD45+ leukocytes and CD163+ macrophages. The extent of the inflammatory cells (leukocytes and macrophages) was semiquantitatively assessed using a 0 -to -4 grade scale as follows: absent (0t), mild (t), moderate (tt), severe (ttt), and very severe (tttt). Serum levels of myokines: irisin, myostatin, IL -8, and lL-6 were determined with multiplex bead -based immunoassay. Results: 119 patients (mean age: 67.58 +/- 9.60 years old, 79.80% males) 64 with claudication and 54 with CLTI were enrolled in the study. No differences were registered between patients with claudication and those with CLTI on age, gender, cardiovascular risk factors, and medication, except on smoking habits. There was a significantly higher prevalence of smokers and a higher smoking load in the claudication group. Samples of sartorius skeletal muscle from 40 patients (14 with claudication and 26 with CLTI) were submitted to histological analysis. No differences were found in skeletal muscle fibers preservation, trauma, or hemorrhage (on hematoxylin-eosin staining). However, in the immunohistochemistry study, we found more inflammatory cells CD45+ leukocytes in patients with CLTI when compared to those with claudication [CD45+ > moderate (tt): claudication (n = 14): 4; 28.57%; CLTI (n = 25): 16; 64.00%; P = 0.034]. Patients with CLTI also had higher tissue levels of CD163+ macrophages, but this difference was not significant [CD163+ > moderate (tt): claudication (n = 13): 7; 53.85%; CLTI (n = 27): 21; 77.78%; P = 0.122]. The serum levels of the myokines, irisin, and myostatin were below the lower limit of detection, in the majority of patients, so no valid results were obtained. However, patients with CLTI had a higher serum level of Interleukin (IL) -6 and IL -8. Conclusions: CLTI patients exhibit increased quantities of leukocytes in their sartorius muscle, as well as elevated serum levels of myokines IL -8 and IL -6. Inflamed skeletal muscle can contribute to the loss of muscle mass and account for the lower density of skeletal muscle observed in CLTI. Additionally, inflamed skeletal muscle may contribute to the development of systemic inflammation through the secretion of pro -inflammatory cytokines into the systemic circulation. Halting the inflammatory process could eventually improve the prognosis of CLTI patients.eng
dc.description.indexMEDLINE
dc.description.indexPubMed
dc.description.indexScopus
dc.description.indexDimensions
dc.description.indexWoS
dc.description.sponsorshipNorthern Portugal Regional Operational Program under the Portugal Partnership Agreement, through the European Regional Development Fund (FEDER) [NORTE-01e0145-FEDER-000013]
dc.description.sponsorshipNational funds, through the Foundation for Science and Technology (FCT) [UIDB/50026/2020, UIDP/50026/2020]
dc.description.sponsorshipPortuguese Society of Vascular Surgery
dc.identifier.citationANNALS OF VASCULAR SURGERY, v.99, p.10-18, 2024
dc.identifier.doi10.1016/j.avsg.2023.09.094
dc.identifier.eissn1615-5947
dc.identifier.issn0890-5096
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/59095
dc.language.isoeng
dc.publisherELSEVIER SCIENCE INCeng
dc.relation.ispartofAnnals of Vascular Surgery
dc.rightsrestrictedAccesseng
dc.rights.holderCopyright ELSEVIER SCIENCE INCeng
dc.subject.othermyostatineng
dc.subject.othercoagulationeng
dc.subject.otheractivationeng
dc.subject.otherapoptosiseng
dc.subject.otherdiseaseeng
dc.subject.otheririsineng
dc.subject.otherleveleng
dc.subject.wosSurgeryeng
dc.subject.wosPeripheral Vascular Diseaseeng
dc.titleInflammation Is a Histological Characteristic of Skeletal Muscle in Chronic Limb Threatening Ischemiaeng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryPortugal
hcfmusp.affiliation.countryisopt
hcfmusp.author.externalFERREIRA, Joana:Ctr Hosp Univ Sao Joao, Vasc Surg Dept & Physiol & Surg, Porto, Portugal; Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Med, Braga, Portugal; ICVS 3Bs PT Govt Associated Lab, Braga, Portugal; Hosp Senhora Oliveira, Acad Ctr, Guimaraes, Portugal; Hosp Tras Os Montes & Alto Douro Prof Doutor Nuno, Clin Acad Ctr, Vila Real, Portugal; Ctr Hosp Univ Sao Joao, P-4200319 Porto, Portugal
hcfmusp.author.externalAFONSO, Julieta:Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Med, Braga, Portugal; ICVS 3Bs PT Govt Associated Lab, Braga, Portugal
hcfmusp.author.externalROQUE, Susana:Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Med, Braga, Portugal; ICVS 3Bs PT Govt Associated Lab, Braga, Portugal
hcfmusp.author.externalCARNEIRO, Alexandre:Radiol Dept, Unidade Local Saude Alto Minho, Viana Do Castelo, Portugal
hcfmusp.author.externalVILE, Isabel:Hosp Senhora Oliveira, Acad Ctr, Guimaraes, Portugal; Hosp Senhora Oliveira, Med Dept, Guimaraes, Portugal; Hosp Senhora Oliveira, Ctr Res & Treatment Arterial Hypertens & Cardiovas, Internal Med Dept, Guimaraes, Portugal
hcfmusp.author.externalSILVA, Cristina:Hosp Senhora Oliveira, Acad Ctr, Guimaraes, Portugal; Hosp Senhora Oliveira, Med Dept, Guimaraes, Portugal; Hosp Senhora Oliveira, Ctr Res & Treatment Arterial Hypertens & Cardiovas, Internal Med Dept, Guimaraes, Portugal
hcfmusp.author.externalCUNHA, Cristina:Hosp Senhora Oliveira, Acad Ctr, Guimaraes, Portugal; Hosp Senhora Oliveira, Med Dept, Guimaraes, Portugal; Hosp Senhora Oliveira, Ctr Res & Treatment Arterial Hypertens & Cardiovas, Internal Med Dept, Guimaraes, Portugal
hcfmusp.author.externalCOTTER, Jorge:Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Med, Braga, Portugal; ICVS 3Bs PT Govt Associated Lab, Braga, Portugal; Hosp Senhora Oliveira, Acad Ctr, Guimaraes, Portugal; Hosp Senhora Oliveira, Med Dept, Guimaraes, Portugal; Hosp Senhora Oliveira, Ctr Res & Treatment Arterial Hypertens & Cardiovas, Internal Med Dept, Guimaraes, Portugal
hcfmusp.author.externalCORREIA-NEVES, Margarida:Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Med, Braga, Portugal; ICVS 3Bs PT Govt Associated Lab, Braga, Portugal
hcfmusp.author.externalMANSILHA, Armando:Ctr Hosp Univ Sao Joao, Vasc Surg Dept & Physiol & Surg, Porto, Portugal; Hosp Senhora Oliveira, Vasc Surg Dept, Guimaraes, Portugal; Ctr Hosp Univ Porto, Dept Angiol & Vasc Surg, Porto, Portugal; Univ Porto, Fac Med, Porto, Portugal
hcfmusp.author.externalCUNHA, Pedro:Univ Minho, Life & Hlth Sci Res Inst ICVS, Sch Med, Braga, Portugal; ICVS 3Bs PT Govt Associated Lab, Braga, Portugal; Hosp Senhora Oliveira, Acad Ctr, Guimaraes, Portugal; Hosp Senhora Oliveira, Med Dept, Guimaraes, Portugal; Hosp Senhora Oliveira, Ctr Res & Treatment Arterial Hypertens & Cardiovas, Internal Med Dept, Guimaraes, Portugal
hcfmusp.citation.scopus1
hcfmusp.contributor.author-fmusphcADHEMAR LONGATTO FILHO
hcfmusp.description.beginpage10
hcfmusp.description.endpage18
hcfmusp.description.volume99
hcfmusp.origemWOS
hcfmusp.origem.dimensionspub.1165578848
hcfmusp.origem.pubmed37931803
hcfmusp.origem.scopus2-s2.0-85178221468
hcfmusp.origem.wosWOS:001168235400001
hcfmusp.publisher.cityNEW YORKeng
hcfmusp.publisher.countryUSAeng
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