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Biomarkers and Proteomics in Sarcomeric Hypertrophic Cardiomyopathy in the Young—FGF-21 Highly Associated with Overt Disease

Österberg, Anna Wålinder ; Östman-Smith, Ingegerd ; Green, Henrik ; Gunnarsson, Cecilia ; Fredrikson, Mats ; Liuba, Petru LU and Fernlund, Eva LU orcid (2024) In Journal of cardiovascular development and disease 11(4).
Abstract

Background: Any difference in biomarkers between genotype-positive individuals with overt hypertrophic cardiomyopathy (HCM), and genotype-positive but phenotype-negative individuals (G+P-) in HCM-associated pathways might shed light on pathophysiological mechanisms. We studied this in young HCM patients. Methods: 29 HCM patients, 17 G+P--individuals, and age- and sex-matched controls were prospectively included. We analyzed 184 cardiovascular disease-associated proteins by two proximity extension assays, categorized into biological pathways, and analyzed with multivariate logistic regression analysis. Significant proteins were dichotomized into groups above/below median concentration in control group. Results: Dichotomized values of... (More)

Background: Any difference in biomarkers between genotype-positive individuals with overt hypertrophic cardiomyopathy (HCM), and genotype-positive but phenotype-negative individuals (G+P-) in HCM-associated pathways might shed light on pathophysiological mechanisms. We studied this in young HCM patients. Methods: 29 HCM patients, 17 G+P--individuals, and age- and sex-matched controls were prospectively included. We analyzed 184 cardiovascular disease-associated proteins by two proximity extension assays, categorized into biological pathways, and analyzed with multivariate logistic regression analysis. Significant proteins were dichotomized into groups above/below median concentration in control group. Results: Dichotomized values of significant proteins showed high odds ratio (OR) in overt HCMphenotype for Fibroblast growth factor-21 (FGF-21) 10 (p = 0.001), P-selectin glycoprotein ligand-1 (PSGL-1) OR 8.6 (p = 0.005), and Galectin-9 (Gal-9) OR 5.91 (p = 0.004). For G+P-, however, angiopoietin-1 receptor (TIE2) was notably raised, OR 65.5 (p = 0.004), whereas metalloproteinase inhibitor 4 (TIMP4) involved in proteolysis, in contrast, had reduced OR 0.06 (p = 0.013). Conclusions: This study is one of the first in young HCM patients and G+P- individuals. We found significantly increased OR for HCM in FGF-21 involved in RAS-MAPK pathway, associated with cardiomyocyte hypertrophy. Upregulation of FGF-21 indicates involvement of the RAS-MAPK pathway in HCM regardless of genetic background, which is a novel finding.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
biomarkers, familial hypertrophic cardiomyopathy, genotype, phenotype, proteomics
in
Journal of cardiovascular development and disease
volume
11
issue
4
article number
105
publisher
MDPI AG
external identifiers
  • scopus:85191684958
ISSN
2308-3425
DOI
10.3390/jcdd11040105
language
English
LU publication?
yes
id
3f403057-af88-4ec4-88da-d9731f0c4f3a
date added to LUP
2024-05-14 13:48:45
date last changed
2024-05-14 13:48:59
@article{3f403057-af88-4ec4-88da-d9731f0c4f3a,
  abstract     = {{<p>Background: Any difference in biomarkers between genotype-positive individuals with overt hypertrophic cardiomyopathy (HCM), and genotype-positive but phenotype-negative individuals (G+P-) in HCM-associated pathways might shed light on pathophysiological mechanisms. We studied this in young HCM patients. Methods: 29 HCM patients, 17 G+P--individuals, and age- and sex-matched controls were prospectively included. We analyzed 184 cardiovascular disease-associated proteins by two proximity extension assays, categorized into biological pathways, and analyzed with multivariate logistic regression analysis. Significant proteins were dichotomized into groups above/below median concentration in control group. Results: Dichotomized values of significant proteins showed high odds ratio (OR) in overt HCMphenotype for Fibroblast growth factor-21 (FGF-21) 10 (p = 0.001), P-selectin glycoprotein ligand-1 (PSGL-1) OR 8.6 (p = 0.005), and Galectin-9 (Gal-9) OR 5.91 (p = 0.004). For G+P-, however, angiopoietin-1 receptor (TIE2) was notably raised, OR 65.5 (p = 0.004), whereas metalloproteinase inhibitor 4 (TIMP4) involved in proteolysis, in contrast, had reduced OR 0.06 (p = 0.013). Conclusions: This study is one of the first in young HCM patients and G+P- individuals. We found significantly increased OR for HCM in FGF-21 involved in RAS-MAPK pathway, associated with cardiomyocyte hypertrophy. Upregulation of FGF-21 indicates involvement of the RAS-MAPK pathway in HCM regardless of genetic background, which is a novel finding.</p>}},
  author       = {{Österberg, Anna Wålinder and Östman-Smith, Ingegerd and Green, Henrik and Gunnarsson, Cecilia and Fredrikson, Mats and Liuba, Petru and Fernlund, Eva}},
  issn         = {{2308-3425}},
  keywords     = {{biomarkers; familial hypertrophic cardiomyopathy; genotype; phenotype; proteomics}},
  language     = {{eng}},
  number       = {{4}},
  publisher    = {{MDPI AG}},
  series       = {{Journal of cardiovascular development and disease}},
  title        = {{Biomarkers and Proteomics in Sarcomeric Hypertrophic Cardiomyopathy in the Young—FGF-21 Highly Associated with Overt Disease}},
  url          = {{http://dx.doi.org/10.3390/jcdd11040105}},
  doi          = {{10.3390/jcdd11040105}},
  volume       = {{11}},
  year         = {{2024}},
}