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Updated: Feb 7, 2026
In Silico Clinical Trials for Cardiovascular Disease
Published on: May 27, 2022
Current IGFBP-Related Biomarker Research in Cardiovascular Disease-We Need More Structural and Functional Information
Andreas Hoeflich1, Robert David2,3, Rikke Hjortebjerg4,5
1Department of Genome Biology, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany.
Insights
Insulin-like growth factor binding proteins (IGFBPs) show potential as cardiovascular disease biomarkers. Current research limitations highlight the need for better analytical methods to understand their complex roles in heart conditions.
Area of Science:
- Biochemistry
- Cardiology
- Endocrinology
Background:
- Cardiovascular diseases (CVDs) are a leading global cause of mortality.
- The insulin-like growth factor (IGF) system, including IGF binding proteins (IGFBPs), plays a role in atherosclerosis and cardiac pathology.
- IGFBPs modulate IGF bioactivity and half-life, with potential IGF-independent functions and complex hormonal regulation.
Purpose of the Study:
- To review the role of IGFBPs as biomarkers in cardiovascular diseases.
- To highlight the challenges and limitations in current IGFBP biomarker research.
- To emphasize the need for improved analytical methods and a deeper understanding of the IGF-IGFBP system in CVDs.
Main Methods:
- Literature review focusing on studies investigating IGFBPs in cardiovascular health and disease.
- Analysis of the dual role of IGFBPs in tissue and circulation.
- Discussion of regulatory factors including hormones, posttranslational modifications, and proteases.
Main Results:
- Circulating IGFBP levels have shown associations with cardiac parameters in various studies.
- Complex hormonal control and posttranslational modifications of IGFBPs contribute to inconsistent findings in large populations.
- Current analytical methods often fail to distinguish between intact and fragmented IGFBPs, a significant limitation.
Conclusions:
- Selected IGFBPs or IGFBP signatures hold promise for identifying cardiac pathophysiology and cardiovascular risk in specific cohorts.
- A comprehensive understanding of the dynamic IGF-IGFBP system, including proteases, is crucial for advancing their use as reliable biomarkers.
- Future research must focus on advanced analytical techniques and a more integrated view of the IGF-IGFBP system in cardiovascular medicine.
Abstract:
Cardiovascular diseases are the leading cause of death around the world and the insulin-like growth factor (IGF)-system has multiple functions for the pathological conditions of atherosclerosis. IGF binding proteins (IGFBPs) are widely investigated as biomarkers for pathological disorders, including those of the heart. At the tissue level, IGFBP-1 to -6 decrease bioactivity of IGF-I and -II due to their high affinity IGF-binding sites. By contrast, in the circulation, the IGFBPs increase biological half-life of the IGFs and may therefore be regarded as positive regulators of IGF-effects. The IGFBPs may also exert IGF-independent functions inside or outside the cell. Importantly, the circulating IGFBP-concentrations are regulated by trophic, metabolic, and reproductive hormones. In a multitude of studies of healthy subjects and patients with coronary heart diseases, various significant associations between circulating IGFBP-levels and defined parameters have been reported. However, the complex hormonal and conditional control of IGFBPs may explain the lack of clear associations between IGFBPs and parameters of cardiac failure in broader studies including larger populations. Furthermore, the IGFBPs are subject to posttranslational modifications and proteolytic degradation by proteases, upon which the IGFs are released. In this review, we emphasize that, with the exception of IGFBP-4 and in sharp contrast to the preclinical studies, virtually all clinical studies do not have structural or functional information on their biomarker. The use of analytical systems with no discriminatory potential toward intact vs. fragmented IGFBPs represents a major issue in IGFBP-related biomarker research and an important focus point for the future. Overall, measurements of selected IGFBPs or more complex IGFBP-signatures of the family of IGFBPs have potential to identify pathophysiological alterations in the heart or patients with high cardiovascular risk, particularly if defined cohorts are to be assessed. However, a more thorough understanding of the dynamic IGF-IGFBP system as well as its proteases and protease inhibitors in both normal physiology and in cardiovascular diseases is necessary.
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