2024-03-28T12:04:57Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/103262022-11-03T13:10:57Zcom_20.500.12105_2152com_20.500.12105_2051com_20.500.12105_2144com_20.500.12105_2145col_20.500.12105_2153col_20.500.12105_2146
Repisalud
author
Martínez-López, Diego
author
Roldan-Montero, Raquel
author
Garcia-Marques, Fernando
author
Nunez, Estefania
author
Jorge, Inmaculada
author
Camafeita, Emilio
author
Minguez, Pablo
author
Rodriguez de Cordoba, Santiago
author
Lopez-Melgar, Beatriz
author
Lara-Pezzi, Enrique
author
Fernandez-Ortiz, Antonio
author
Ibáñez, Borja
author
Valdivielso, Jose Manuel
author
Fuster, Valentin
author
Michel, Jean-Baptiste
author
Blanco-Colio, Luis Miguel
author
Vazquez, Jesus
author
Martin-Ventura, Jose Luis
funder
Ministerio de Economía y Competitividad (España)
funder
Comunidad de Madrid (España)
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Fundación La Caixa
funder
Banco Santander
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Fundación ProCNIC
2020-06-10T11:36:38Z
2020-06-10T11:36:38Z
2020-04-28
J Am Coll Cardiol. 2020; 75(16):1926-1941
http://hdl.handle.net/20.500.12105/10326
32327104
10.1016/j.jacc.2020.02.058
1558-3597
Journal of the American College of Cardiology
The mechanisms underlying early atherosclerotic plaque formation are not completely understood. Moreover, plasma biomarkers of subclinical atherosclerosis are lacking.
The purpose of this study was to analyze the temporal and topologically resolved protein changes taking place in human aortas with early atherosclerosis to find new potential diagnostic and/or therapeutic targets.
The protein composition of healthy aortas (media layer) or with early atheroma (fatty streak and fibrolipidic, media and intima layers) was analyzed by deep quantitative multiplexed proteomics. Further analysis was performed by Western blot, immunohistochemistry, real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. Plasma levels of complement C5 were analyzed in relation to the presence of generalized (>2 plaques) or incipient (0 to 2 plaques) subclinical atherosclerosis in 2 independent clinical cohorts (PESA [Progression of Early Subclinical Atherosclerosis] [n = 360] and NEFRONA [National Observatory of Atherosclerosis in Nephrology] [n = 394]).
Proteins involved in lipid transport, complement system, immunoglobulin superfamily, and hemostasis are increased in early plaques. Components from the complement activation pathway were predominantly increased in the intima of fibrolipidic plaques. Among them, increased C5 protein levels were further confirmed by Western blot, enzyme-linked immunosorbent assay and immunohistochemistry, and associated with in situ complement activation. Plasma C5 was significantly increased in individuals with generalized subclinical atherosclerosis in both PESA and NEFRONA cohorts, independently of risk factors. Moreover, in the PESA study, C5 plasma levels positively correlated with global plaque volume and coronary calcification.
Activation of the complement system is a major alteration in early atherosclerotic plaques and is reflected by increased C5 plasma levels, which have promising value as a novel circulating biomarker of subclinical atherosclerosis.
eng
Complement C5 Protein as a Marker of Subclinical Atherosclerosis.
journal article
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URL
https://repisalud.isciii.es/bitstream/20.500.12105/10326/1/ComplementC5ProteinMarker_2020.pdf
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ComplementC5ProteinMarker_2020.pdf
URL
https://repisalud.isciii.es/bitstream/20.500.12105/10326/6/ComplementC5ProteinMarker_2020.pdf.txt
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ComplementC5ProteinMarker_2020.pdf.txt