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Proteomics of left ventricular structure in the Multi-Ethnic Study of Atherosclerosis.
Peterson, Tess E; Lima, Joao A C; Shah, Sanjiv J; Bluemke, David A; Bertoni, Alain G; Liu, Yongmei; Ngo, Debby; Varadarajan, Vinithra; Mychaleckyj, Josyf C; Johnson, Craig W; Psaty, Bruce M; Clish, Clary B; Taylor, Kent D; Durda, Peter; Tracy, Russell P; Gerszten, Robert E; Rich, Stephen S; Rotter, Jerome I; Post, Wendy S; Pankow, James S.
Afiliación
  • Peterson TE; Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
  • Lima JAC; Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
  • Shah SJ; Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
  • Bluemke DA; Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
  • Bertoni AG; Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
  • Liu Y; Department of Medicine, Cardiology and Neurology, Duke University Medical Center, Durham, North Carolina, USA.
  • Ngo D; Division of Cardiovascular Medicine, Beth Israel Deaconess Hospital, Boston, Massachusetts, USA.
  • Varadarajan V; Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
  • Mychaleckyj JC; Department of Genome Sciences, University of Virginia, Charlottesville, Virginia, USA.
  • Johnson CW; Department of Biostatistics, University of Washington, Seattle, Washington, USA.
  • Psaty BM; Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Systems and Population Health, University of Washington, Seattle, Washington, USA.
  • Clish CB; Metabolomics Platform, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Washington, USA.
  • Taylor KD; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, USA.
  • Durda P; Department of Pathology & Laboratory Medicine, University of Vermont, Colchester, Vermont, USA.
  • Tracy RP; Department of Pathology & Laboratory Medicine, University of Vermont, Colchester, Vermont, USA.
  • Gerszten RE; Division of Cardiovascular Medicine, Beth Israel Deaconess Hospital, Boston, Massachusetts, USA.
  • Rich SS; Department of Genome Sciences, University of Virginia, Charlottesville, Virginia, USA.
  • Rotter JI; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, USA.
  • Post WS; Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
  • Pankow JS; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
ESC Heart Fail ; 2024 Sep 12.
Article en En | MEDLINE | ID: mdl-39263947
ABSTRACT

AIMS:

Proteomic profiling offers an expansive approach to biomarker discovery and mechanistic hypothesis generation for LV remodelling, a critical component of heart failure (HF). We sought to identify plasma proteins cross-sectionally associated with left ventricular (LV) size and geometry in a diverse population-based cohort without known cardiovascular disease (CVD). METHODS AND

RESULTS:

Among participants of the Multi-Ethnic Study of Atherosclerosis (MESA), we quantified plasma abundances of 1305 proteins using an aptamer-based platform at exam 1 (2000-2002) and exam 5 (2010-2011) and assessed LV structure by cardiac magnetic resonance (CMR) at the same time points. We used multivariable linear regression with robust variance to assess cross-sectional associations between plasma protein abundances and LV structural characteristics at exam 1, reproduced findings in later-life at exam 5, and explored relationships of associated proteins using annotated enrichment analysis. We studied 763 participants (mean age 60 ± 10 years at exam 1; 53% female; 19% Black race; 31% Hispanic ethnicity). Following adjustment for renal function and traditional CVD risk factors, plasma levels of 3 proteins were associated with LV mass index at both time points with the same directionality (FDR < 0.05) leptin (LEP), renin (REN), and cathepsin-D (CTSD); 20 with LV end-diastolic volume index LEP, NT-proBNP, histone-lysine N-methyltransferase (EHMT2), chordin-like protein 1 (CHRDL1), tumour necrosis factor-inducible gene 6 protein (TNFAIP6), NT-3 growth factor receptor (NTRK3), c5a anaphylatoxin (C5), neurogenic locus notch homologue protein 3 (NOTCH3), ephrin-B2 (EFNB2), osteomodulin (OMD), contactin-4 (CNTN4), gelsolin (GSN), stromal cell-derived factor 1 (CXCL12), calcineurin subunit B type 1 (PPP3R1), insulin-like growth factor 1 receptor (IGF1R), bone sialoprotein 2 (IBSP), interleukin-11 (IL-11), follistatin-related protein 1 (FSTL1), periostin (POSTN), and biglycan (BGN); and 4 with LV mass-to-volume ratio RGM domain family member B (RGMB), transforming growth factor beta receptor type 3 (TGFBR3), ephrin-A2 (EFNA2), and cell adhesion molecule 3 (CADM3). Functional annotation implicated regulation of the PI3K-Akt pathway, bone morphogenic protein signalling, and cGMP-mediated signalling.

CONCLUSIONS:

We report proteomic profiling of LV size and geometry, which identified novel associations and reinforced previous findings on biomarker candidates for LV remodelling and HF. If validated, these proteins may help refine risk prediction and identify novel therapeutic targets for HF.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: ESC Heart Fail Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: ESC Heart Fail Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido