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Correlation of adrenomedullin gene expression in peripheral blood leukocytes with severity of ischemic stroke
Jia Liu1, Jun Yan, Judith M Greer
11The University of Queensland , UQ Centre for Clinical Research.
Abstract:
Human adrenomedullin (ADM), a 52-amino acid peptide, belongs to the calcitonin/calcitonin gene-related peptide (CGRP)/amylin peptide family. ADM acts as a multifunctional regulatory peptide and is upregulated in response to hypoxia. Previous microarray studies have found increased ADM gene (ADM) expression in peripheral blood cells of patients with stroke, however, it is unknown if an increased ADM level is correlated with severity of human ischemic stroke. This study investigated ADM expression in peripheral blood leukocytes (PBL) of healthy controls and subjects at day 1, week 1 and week 3 postacute ischemic stroke using rtPCR methodology. We found that ADM expression was significantly upregulated on the first day of stroke compared to the healthy subjects and the disease controls; the levels remained elevated for up to week 3. Further, ADM expression at day 1 was correlated with stroke severity measured by the National Institute of Healthy Stroke Scale (NIHSS), the modified Barthel Index (mBI) and the modified Rankin Scale (mRS). This could indicate that ADM expression level is related to the severity of tissue damage. We suggest that increased ADM expression in PBL after acute ischemic stroke is most likely to indicate that these cells have been subjected to hypoxia and that the magnitude of expression is likely to be related to the volume of hypoxic tissue. Hypoxia can affect lymphocytes function and could affect the immune response to stroke. The correlation of ADM expression level with the measures of stroke severity implicates ADM--a potential blood bio-marker in studies of ischemic stroke.
Insights
Adrenomedullin (ADM) levels in blood cells are elevated after ischemic stroke, correlating with stroke severity. This suggests ADM may serve as a biomarker for hypoxic tissue damage and immune response in stroke patients.
Area of Science:
- Biochemistry
- Neuroscience
- Immunology
Background:
- Human adrenomedullin (ADM) is a peptide hormone involved in regulating physiological processes.
- ADM expression is known to increase under hypoxic conditions.
- Previous studies indicated elevated ADM gene expression in stroke patients' blood cells.
Purpose of the Study:
- To investigate the correlation between ADM expression levels in peripheral blood leukocytes (PBL) and the severity of acute ischemic stroke.
- To determine if ADM expression is a reliable biomarker for stroke severity and hypoxic tissue damage.
Main Methods:
- Quantitative real-time PCR (rtPCR) was used to measure ADM expression in PBL from healthy controls and ischemic stroke patients at different time points (day 1, week 1, week 3).
- Stroke severity was assessed using established clinical scales: National Institute of Health Stroke Scale (NIHSS), modified Barthel Index (mBI), and modified Rankin Scale (mRS).
Main Results:
- ADM expression was significantly upregulated in PBL of ischemic stroke patients on day 1 post-stroke compared to healthy controls, remaining elevated for up to 3 weeks.
- ADM expression levels at day 1 positively correlated with stroke severity as measured by NIHSS, mBI, and mRS.
- The magnitude of ADM upregulation appeared related to the extent of hypoxic tissue damage.
Conclusions:
- Increased ADM expression in PBL following acute ischemic stroke is likely a response to cellular hypoxia.
- ADM expression levels correlate with stroke severity, suggesting its potential as a blood biomarker for assessing tissue damage and immune response in stroke.
- ADM may play a role in modulating the immune response to stroke through its effects on lymphocyte function.
