Biomarkers and Proteomics in Sarcomeric Hypertrophic Cardiomyopathy in the Young—FGF-21 Highly Associated with Overt Disease
(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
- Österberg, Anna Wålinder ; Östman-Smith, Ingegerd ; Green, Henrik ; Gunnarsson, Cecilia ; Fredrikson, Mats ; Liuba, Petru LU and Fernlund, Eva LU
- organization
- publishing date
- 2024-04
- 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}}, }