ArticleCardiovascular diabetology2024
Plasma proteome association with coronary heart disease and carotid intima media thickness: results from the KORA F4 study.
Article in Cardiovascular diabetology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed.
- Proteomic Profile After Intervention With Eplerenone Among Persons With HIV.Open forum infectious diseases · 2026Trial
- Plasma proteomic signatures of subclinical atherosclerosis progression for cardiovascular risk stratification: A cohort study.PLoS medicine · 2026Article
- Article
- Targeted plasma proteomics reveals a central role of upregulated TNFRSF proteins in HIV-associated stroke.Nature communications · 2026Article
- Glycobiology-driven therapeutic targeting of glycan-binding proteins: mechanisms, diseases, and clinical translation.Signal transduction and targeted therapy · 2026Review
- Tissue-specific roles of IGFBP2 in glucose and lipid metabolism in obesity-related metabolic diseases.Frontiers in nutrition · 2026Review
- Article
- Immune Inflammation at the Crossroads of Atherosclerosis and Ischemic Stroke: Mechanisms, Trends, and Translational Perspectives.CNS neuroscience & therapeutics · 2025Review
- Association of Elevated Galectin-4 Concentrations with Obesity, Diabetes, and Cardiovascular Diseases.International journal of molecular sciences · 2025Review
- Emerging Biomarkers and Determinants of Lipoprotein Profiles to Predict CVD Risk: Implications for Precision Nutrition.Nutrients · 2024Review
- Plasma proteomics and carotid intima-media thickness in the UK biobank cohort.Frontiers in cardiovascular medicine · 2024Article
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18 authors.
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Abstract
BACKGROUND AND
aimsAtherosclerosis is the main cause of stroke and coronary heart disease (CHD), both leading mortality causes worldwide. Proteomics, as a high-throughput method, could provide helpful insights into the pathological mechanisms underlying atherosclerosis. In this study, we characterized the associations of plasma protein levels with CHD and with carotid intima-media thickness (CIMT), as a surrogate measure of atherosclerosis.
methodsThe discovery phase included 1000 participants from the KORA F4 study, whose plasma protein levels were quantified using the aptamer-based SOMAscan proteomics platform. We evaluated the associations of plasma protein levels with CHD using logistic regression, and with CIMT using linear regression. For both outcomes we applied two models: an age-sex adjusted model, and a model additionally adjusted for body mass index, smoking status, physical activity, diabetes status, hypertension status, low density lipoprotein, high density lipoprotein, and triglyceride levels (fully-adjusted model). The replication phase included a matched case-control sample from the independent KORA F3 study, using ELISA-based measurements of galectin-4. Pathway analysis was performed with nominally associated proteins (p-value < 0.05) from the fully-adjusted model.
resultsIn the KORA F4 sample, after Bonferroni correction, we found CHD to be associated with five proteins using the age-sex adjusted model: galectin-4 (LGALS4), renin (REN), cathepsin H (CTSH), and coagulation factors X and Xa (F10). The fully-adjusted model yielded only the positive association of galectin-4 (OR = 1.58, 95% CI = 1.30-1.93), which was successfully replicated in the KORA F3 sample (OR = 1.40, 95% CI = 1.09-1.88). For CIMT, we found four proteins to be associated using the age-sex adjusted model namely: cytoplasmic protein NCK1 (NCK1), insulin-like growth factor-binding protein 2 (IGFBP2), growth hormone receptor (GHR), and GDNF family receptor alpha-1 (GFRA1). After assessing the fully-adjusted model, only NCK1 remained significant (β = 0.017, p-value = 1.39e-06). Upstream regulators of galectin-4 and NCK1 identified from pathway analysis were predicted to be involved in inflammation pathways.
conclusionsOur proteome-wide association study identified galectin-4 to be associated with CHD and NCK1 to be associated with CIMT. Inflammatory pathways underlying the identified associations highlight the importance of inflammation in the development and progression of CHD.
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