Blood Differential Gene Expression in Patients with Chronic Heart Failure and Systemic Iron Deficiency: Pathways Involved in Pathophysiology and Impact on Clinical Outcomes
| Autor: | José González-Costello, Elena García-Romero, Sergi Yun Viladomat, Pedro Moliner Borja, Marta Tajes Orduña, Carles Díez-López, Santiago Jiménez-Marrero, Raul Ramos-Polo, Josep Francesch Manzano, Cristina Enjuanes Grau, Maria del Mar Ras Jiménez, Josep Comín-Colet |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
heart failure
Heart failure Insuficiència cardíaca Bioinformatics Article Mitocondris Transcriptome cardiac metabolism iron deficiency Gene expression medicine Dèficit de ferro business.industry MITOCHONDRIAL FERRITIN General Medicine Iron deficiency medicine.disease Cardiovascular physiology Mitochondria mitochondria Cohort Iron deficiency diseases Medicine Small integral membrane protein 20 business |
| Zdroj: | Journal of Clinical Medicine Volume 10 Issue 21 Journal of Clinical Medicine, Vol 10, Iss 4937, p 4937 (2021) Dipòsit Digital de la UB Universidad de Barcelona |
| ISSN: | 2077-0383 |
| DOI: | 10.3390/jcm10214937 |
| Popis: | Background: Iron deficiency is a common disorder in patients with heart failure and is related with adverse outcomes and poor quality of life. Previous experimental studies have shown biological connections between iron homeostasis, mitochondrial metabolism, and myocardial function. However, the mechanisms involved in this crosstalk are yet to be unfolded. Methods: The present research attempts to investigate the intrinsic biological mechanisms between heart failure and iron deficiency and to identify potential prognostic biomarkers by determining the gene expression pattern in the blood of heart failure patients, using whole transcriptome and targeted TaqMan® low-density array analyses. Results: We performed a stepwise cross-sectional longitudinal study in a cohort of chronic heart failure patients with and without systemic iron deficiency. First, the full transcriptome was performed in a nested case-control exploratory cohort of 7 paired patients and underscored 1128 differentially expressed transcripts according to iron status (cohort1#). Later, we analyzed the messenger RNA levels of 22 genes selected by their statistical significance and pathophysiological relevance, in a validation cohort of 71 patients (cohort 2#). Patients with systemic iron deficiency presented lower mRNA levels of mitochondrial ferritin, sirtuin-7, small integral membrane protein 20, adrenomedullin and endothelin converting enzyme-1. An intermediate mitochondrial ferritin gene expression and an intermediate or low sirtuin7 and small integral membrane protein 20 mRNA levels were associated with an increased risk of all-cause mortality and heart failure admission ((HR 2.40, 95% CI 1.04–5.50, p-value = 0.039), (HR 5.49, 95% CI 1.78–16.92, p-value = 0.003), (HR 9.51, 95% CI 2.69–33.53, p-value < 0.001), respectively). Conclusions: Patients with chronic heart failure present different patterns of blood gene expression depending on systemic iron status that affect pivotal genes involved in iron regulation, mitochondrial metabolism, endothelial function and cardiovascular physiology, and correlate with adverse clinical outcomes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|