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Updated: May 6, 2026
Ultrasonic Assessment of Myocardial Microstructure
Published on: January 14, 2014
Proteomics of left ventricular structure in the Multi-Ethnic Study of Atherosclerosis
Tess E Peterson1, Joao A C Lima1, Sanjiv J Shah2
1Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Insights
Proteomic profiling identified novel plasma protein associations with left ventricular (LV) remodeling in a diverse cohort. These findings may improve heart failure (HF) risk prediction and reveal new therapeutic targets.
Area of Science:
- Cardiovascular proteomics
- Biomarker discovery
- Heart failure mechanisms
Background:
- Left ventricular (LV) remodeling is central to heart failure (HF) pathogenesis.
- Proteomic profiling offers a comprehensive approach for identifying biomarkers and generating mechanistic hypotheses for LV remodeling.
Purpose of the Study:
- To identify plasma proteins associated with LV size and geometry in a diverse population without known cardiovascular disease (CVD).
- To explore potential biomarkers for LV remodeling and subsequent HF development.
Main Methods:
- Quantified 1305 plasma proteins using aptamer-based technology in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort.
- Assessed LV structure via cardiac magnetic resonance (CMR) at two time points.
- Employed multivariable regression to identify cross-sectional associations, validated findings over time, and used enrichment analysis.
Main Results:
- Identified 3 proteins (leptin, renin, cathepsin-D) associated with LV mass index at both time points.
- Found 20 proteins linked to LV end-diastolic volume index and 4 proteins to LV mass-to-volume ratio.
- Enrichment analysis implicated pathways like PI3K-Akt, bone morphogenic protein, and cGMP-mediated signaling.
Conclusions:
- This proteomic profiling study reveals novel associations with LV size and geometry.
- Identified protein candidates may enhance risk prediction and offer therapeutic targets for LV remodeling and HF.
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.
