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Extracellular volume by CMR is associated with serum biomarkers of extracellular matrix turnover and inflammation in hypertensive heart disease
Journal of Cardiovascular Magnetic Resonance volume 18, Article number: O103 (2016)
Background
Cardiac biomarkers have become increasingly important in cardiovascular disease. With the ability to detect focal and diffuse myocardial fibrosis, CMR is an important imaging biomarker. Diffuse myocardial fibrosis, reflected by increased extracellular volume (ECV), may underlie increased cardiovascular risk. ECV could provide a novel tool to evaluate the association myocardial-specific fibrosis and serum biomarkers. We hypothesized that ECV would correlate with known cardiovascular serum biomarkers in hypertensive heart disease.
Methods
Patients with a history of hypertension with or without LVH by any non-invasive imaging modality and healthy volunteers (18 HTN, 13 HTN-LVH, and 13 controls) underwent CMR on a Siemens 1.5T Avanto and blood samples were obtained for biomarker analysis. T1 mapping was performed, using a previously validated modified Look-Locker inversion-recovery (MOLLI) pulse sequence, before 0.15 mmol/kg gadolinium DTPA (native T1) and at 10, 15, and 20 min post-contrast. Mean ECV and native T1 values were determined. Biomarkers were analyzed using the Proseek Multiplex CVD 96 × 96 (Olink Bioscience, Uppsala, Sweden). CMR parameters were compared with blood biomarkers via Pearson's correlation.
Results
Mean age was 57 ± 7, 64 ± 13, and 57 ± 12 for control, HTN, and HTN-LVH groups, respectively. LV mass index (LVMI) (g/m2) was 49.0 ± 6.8, 54.7 ± 10.6, and 82.8 ± 14.1* and ECV was 0.25 ± 0.02, 0.26 ± 0.03, 0.30 ± 0.03* (*p < 0.05 vs. controls and HTN) respectively. Matrix metalloproteinase 7 (MMP-7), C-X-C motif chemokine 1 (CXCL1), and fatty acid binding protein 4 (FABP4) had the highest correlation with ECV in all groups (r values: 0.46; 0.45; 0.44; respectively, p < 0.005 for all) (Fig 1 [CK1]). LVMI was highly correlated with T cell immunoglobulin and mucin domain (TIM-1) and MMP-7 as well (r values: 0.55; 0.46; respectively, p < 0.005 for all).
Conclusions
Increased ECV, seen in patients with HTN-LVH, corresponds with diffuse fibrosis and may be due in large part to systemic inflammation and resulting alterations and remodeling of the extracellular matrix. MMP-7 is involved in extracellular matrix remodeling and is known to be upregulated in cardiac fibrosis and LVH. CXCL-1 and FABP4 also play a role in inflammation. Recent evidence suggests that FABP4 is involved in the integration of metabolic and inflammatory pathways and may play important roles in insulin resistance, atherosclerosis and diastolic dysfunction. The novel finding of the correlation with ECV with these markers suggests a link between altered metabolism and inflammation with cardiac fibrosis.
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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Shaw, P.W., Yang, Y., Gonzalez, J.A. et al. Extracellular volume by CMR is associated with serum biomarkers of extracellular matrix turnover and inflammation in hypertensive heart disease. J Cardiovasc Magn Reson 18 (Suppl 1), O103 (2016). https://doi.org/10.1186/1532-429X-18-S1-O103
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DOI: https://doi.org/10.1186/1532-429X-18-S1-O103
Keywords
- Cardiac Fibrosis
- Fatty Acid Binding
- Extracellular Volume
- Hypertensive Heart Disease
- Extracellular Matrix Remodel