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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

ApoC-III is a novel inducer of calcification in human aortic valves

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Autor(es):
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Schlotter, Florian [1] ; Freitas, Renata C. C. de [1] ; Rogers, Maximillian A. [1] ; Blaser, Mark C. [1] ; Wu, Pin-Jou [1] ; Higashi, Hideyuki [1] ; Halu, Arda [1, 2] ; Iqbal, Farwah [3] ; Andraski, Allison B. [4, 5] ; Rodia, Cayla N. [6] ; Kuraoka, Shiori [1] ; Wen, Jennifer R. [1] ; Creager, Michael [1] ; Pham, Tan ; Hutcheson, Joshua D. [7] ; Body, Simon C. [8] ; Kohan, Alison B. [9] ; Sacks, Frank M. [4, 5] ; Aikawa, Masanori [10, 3] ; Singh, Sasha A. [10] ; Aikawa, Elena [10, 3, 11]
Número total de Autores: 21
Afiliação do(s) autor(es):
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[1] Harvard Med Sch, Div Cardiovasc Med, Dept Med, Ctr Interdisciplinary Cardiovasc Sci, Brigham & Wo, Boston, MA 02115 - USA
[2] Harvard Med Sch, Channing Div Network Med, Brigham & Womens Hosp, Boston, MA 02115 - USA
[3] Harvard Med Sch, Div Cardiovasc Med, Dept Med, Ctr Excellence Vasc Biol, Brigham & Womens Hosp, Boston, MA 02115 - USA
[4] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA - USA
[5] Harvard TH Chan Sch Publ Hlth, Dept Mol Metab, Boston, MA - USA
[6] Univ Connecticut, Dept Nutr Sci, Storrs, CT - USA
[7] Florida Int Univ, Dept Biomed Engn, Miami, FL 33199 - USA
[8] Boston Univ, Dept Anesthesiol, Sch Med, Boston, MA 02118 - USA
[9] Univ Pittsburgh, Div Endocrinol & Metab, Dept Med, Pittsburgh, PA - USA
[10] Tan Pham, Harvard Med Sch, Div Cardiovasc Med, Dept Med, Ctr Interdisciplinary Cardiovasc Sci, Brigham & Wo, Boston, MA 02115 - USA
[11] Sechenov First Moscow State Med Univ, Dept Human Pathol, Moscow - Russia
Número total de Afiliações: 11
Tipo de documento: Artigo Científico
Fonte: Journal of Biological Chemistry; v. 296, JAN-JUN 2021.
Citações Web of Science: 3
Resumo

Calcific aortic valve disease (CAVD) occurs when sub-populations of valve cells undergo specific differentiation pathways, promoting tissue fibrosis and calcification. Lipoprotein particles carry oxidized lipids that promote valvular disease, but low-density lipoprotein-lowering therapies have failed in clinical trials, and there are currently no pharmacological interventions available for this disease. Apolipoproteins are known promoters of atherosclerosis, but whether they possess pathogenic properties in CAVD is less clear. To search for a possible link, we assessed 12 apolipoproteins in nonfibrotic/noncalcific and fibrotic/calcific aortic valve tissues by proteomics and immunohistochemistry to understand if they were enriched in calcified areas. Eight apolipoproteins (apoA-I, apoA-II, apoA-IV, apoB, apoC-III, apoD, apoL-I, and apoM) were enriched in the calcific versus nonfibrotic/noncalcific tissues. Apo(a), apoB, apoC-III, apoE, and apoJ localized within the disease-prone fibrosa and colocalized with calcific regions as detected by immunohistochemistry. Circulating apoC-III on lipoprotein(a) is a potential biomarker of aortic stenosis incidence and progression, but whether apoC-III also induces aortic valve calcification is unknown. We found that apoC-III was increased in fibrotic and calcific tissues and observed within the calcification-prone fibrosa layer as well as around calcification. In addition, we showed that apoC-III induced calcification in primary human valvular cell cultures via a mitochondrial dysfunction/inflammation-mediated pathway. This study provides a first assessment of a broad array of apolipoproteins in CAVD tissues, demonstrates that specific apolipoproteins associate with valvular calcification, and implicates apoC-III as an active and modifiable driver of CAVD beyond its potential role as a biomarker. (AU)

Processo FAPESP: 19/22147-0 - Avaliação do perfil de microRNA-proteína exossomais em pacientes com hipercolesterolemia familiar
Beneficiário:Renata Caroline Costa de Freitas
Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado