Higher Level of Serum Heme Oxygenase-1 in Patients With Intracerebral Hemorrhage

Abstract

The objective of this paper was to investigate the association of the serum level of heme oxygenase-1 in patients with intracerebral hemorrhage (ICH) with the risk of ICH. Heme oxygenase-1(HO-1) metabolizes heme into biliverdin, bilirubin, carbon monoxide, and iron, our recent study showed that serum level of HO-1 was increased in stroke patients, yet the association of HO-1 level with risk of intracerebral hemorrhage (ICH) is poorly known. Forty patients with ICH and another 40 patients without ICH were recruited. The serum level of HO-1, total, and direct bilirubin were measured. The level of HO-1, serum total bilirubin, and direct bilirubin, as well as blood pressure were increased in ICH group than in control group (P , 0.001). The level of HO-1, both systolic and diastolic blood pressure had a significant difference between subgroups (P , 0.05). Multivariate regression analysis showed that poor compliance to medicine for hypertension, the serum level of HO-1, and systolic blood pressure were associated with the prevalence of ICH. Blood pressure, serum HO-1, serum total bilirubin, and direct bilirubin were raised in patients with ICH who did not take medicine for hypertension compared with those who did, and increased in ICH patients in comparison with control group. Further investigation in multiple medical centers with large number of cohorts is warranted to verify these results. Key words: Heme oxygenase-1 -Intracerebral hemorrhage -Bilirubin -Hypertension H eme oxygenase (HO) presents in several mammalian tissues, catalyzes the rate-limiting step in heme degradation, regulates heme protein turnover, and cleaves the heme ring to form biliverdin that is subsequently converted to bilirubin.1,2,3 There are 3 known HO isoforms: HO-1, HO-2, and HO-3. HO-1, a 32-kDa heat shock protein, is inducible by several stress factors such as oxidative stress, hypoxia, heavy metals, etc. In humans, the ho-1 gene (HMOX1) is located on chromosome 22q12 and contains 4 introns and 5 exons. HO-1 enzymes have been characterized as endoplasmic reticulum associated proteins due to the abundant detection of HO activity in microsomal fractions. HO-2 is a constitutive isoform that is expressed under homeostatic conditions. Both HO-1 and HO-2 are ubiquitously expressed and catalytically active. HO-3 is not catalytically active, there are no functional HO-3 genes at least in rats. 4 Expression of HO-1 has been described in microglia, astrocytes, and neurons in many experimental models such as subarachnoid hemorrhage, ischemia and traumatic brain injury, as well as in human neurodegenerative diseases.1 HO-1 has been reported to be associated with prevalence of stroke.5 Our recent study showed that HO-1 level was higher in patients with stroke than with TIA. 6 The stroke can be caused by ischemic infarction or intracerebral hemorrhage (ICH), which is one of the most prominent conditions leading to high morbidity and mortality.7 Bilirubin, a powerful antioxidant, is induced after hemorrhagic stroke, and is significantly elevated in patie...

The role of heme oxygenase-1 (HO-1) in the regulation of inflammatory reaction, neuronal cell proliferation and apoptosis in rats after intracerebral hemorrhage (ICH)

“…At postoperative 30 minutes, ICH rats were treated with 10 mg/kg ZPP and at postoperative day 3, rats were sacrificed and parameters were evaluated. Results showed that HO-1 positive rate and mRNA expression of rats in the ICH group were significantly increased, which is consistent with the study done by Wang et al,9 Li et al17 and Liu et al,18 while ZPP significantly reduced brain tissue HO-1 expression in post ICH rats. Our study also showed that ZPP as HO-1 inhibitor could significantly reduce the neurological function deficit score and brain water content in ICH rats, suggesting that overexpression of HO-1 at day 3 post ICH has an inhibitory effect on the recovery of neurological function and relief of brain edema.…”

“…In a study done by Li et al17 on the level of HO-1 in plasma and total bilirubin in 40 cases of ICH patients and 40 healthy controls, results showed that levels of HO-1 and total bilirubin were significantly higher in the ICH group compared to healthy controls. Multiple regression analysis showed that HO-1 and total bilirubin is closely related to ICH patients.…”

(−)-Epicatechin, a Natural Flavonoid Compound, Protects Astrocytes Against Hemoglobin Toxicity via Nrf2 and AP-1 Signaling Pathways

“…Interestingly, the role of HO1 after ICH is controversial [5]. In ICH patients, HO1 expression in the hemorrhagic brain is associated with CD163 expression at 72 h after ICH [49], and serum HO1 level is increased in ICH patients [50]. In an animal model of ICH, systemic hemin therapy was reported to increase HO1 expression and attenuate blood-brain barrier disruption [51].…”

Effects of virtual reality-based motor control training on inflammation, oxidative stress, neuroplasticity and upper limb motor function in patients with chronic stroke: a randomized controlled trial

“…Such molecular changes could be detected by serum biomarkers. For example, interleukin 6 (IL-6) [ 23 – 26 ] and intercellular adhesion molecule (ICAM-1) could represent the inflammation level [ 23 , 27 , 28 ], 8-hydroxy-2′-deoxyguanosine (8-OHdG) [ 29 , 30 ] and heme oxygenase-1 (HO-1) could provide the information of oxidative stress [ 31 – 35 ], and brain-derived neurotrophic factor (BDNF) could be an indicator of neuroplasticity [ 36 , 37 ].…”