Role Of Haptoglobin Research Articles

Plasma Haptoglobin as A Potential Biomarker for Coronary Artery Disease in Young Hypertensive Adults

INTRODUCTION: Uncontrolled hypertension is one of the recognized risk factors for coronary artery disease (CAD) in young adults, commonly underestimated owing to the young age. A novel biomarker to improve CAD risk assessment and hypertension management should be identified for this cohort. Thus, we had conducted a study to investigate plasma concentration and the role of haptoglobin in young hypertensive adults in the establishment of premature acute myocardial infarction (AMI). MATERIALS AND METHODS: A total of 120 male adults aged between 18 to 45 years enrolled into this cross-sectional study, divided into control, hypertensive, and acute myocardial infarction (AMI) groups. Blood samples were collected from all subjects, plasma concentrations of haptoglobin measured using enzyme-linked immunosorbent assays, and other CAD risk factors including high sensitivity C-reactive protein (hs-CRP) levels were analyzed. RESULTS: Plasma concentration of haptoglobin in the AMI group was the highest compared to hypertensive and control group (290.63±99.90 vs. 208.47±112.93 vs. 170.02±108.11 ng/ml, p<0.006). There was a significant association between AMI and plasma haptoglobin concentration in hypertensive subjects independent of other known CAD risk factors (OR: 0.985, 95% CI 0.973-0.997, p=0.017). There was positive correlation between plasma haptoglobin and hs-CRP (r=0.0370, p<0.001). CONCLUSION: Plasma haptoglobin is a potential biomarker to identify young hypertensive adults who are at risk of developing CAD.

Role of Haptoglobin in Protection from the Toxic Effects of Extracellular Hemoglobin in Various Pathologies

Role of Haptoglobin in Protection from the Toxic Effects of Extracellular Hemoglobin in Various Pathologies

Role of haptoglobin 2-2 genotype on disease progression and mortality among South Indian chronic kidney disease patients.

Haptoglobin (HP), a plasma glycoprotein, binds to free hemoglobin and prevents the loss of iron and kidney damage. The variations of HP gene affect its enzyme activity, resulting in varied antioxidant, angiogenic and anti-inflammatory properties. HP 2-2 genotype showed 3.84 fold increased risk for the development of CKD in Taiwan population. With this background, the present work focused to conduct a prospective case-control study in South Indian population to evaluate whether the HP variants are associated to nondialysis (ND) (CKD stages 1-4) and ESRD (CKD stage 5) conditions. Totally 392 CKD patients (nondialysis, ND; n = 170, end-stage renal disease, ESRD; n = 222) and 202 healthy individuals were enrolled. The blood samples collected from the patients were used to determine biochemical parameters and HP genotyping. Gene frequency and biochemical parameters were statistically analyzed for disease association. Results showed that HP 2-2 genotypes were significantly associated with ND and ESRD disease development compared to controls. Higher HP2-2 genotype frequency showed an increased hazard ratio for overall disease progression among ND patients (hazard ratio = 3.86; 95% CI 1.88 to 7.93; P = 0.0002). Survival analysis also showed that non-HP2-2 patients have a statistically significantly decreased risk for mortality compared to patients with the HP2-2 genotype (ESRD patients hazard ratio = 4.05; P = 0.04). The present study confirms that HP2-2 polymorphism is statistically associated with the risk of CKD incidence, progression, and mortality among South Indians. Concluding our results, the HP2-2 genotype could be an independent predictor of all-cause mortality and disease progression in patients with CKD.

The role of haptoglobin in the diagnosis of preeclampsia and HELLP syndrome and in predicting neonatal outcomes.

The study aimed to determine whether maternal serum haptoglobin values could have an effect on predicting diagnosis and neonatal outcomes in preeclampsia and HELLP syndrome. Hundred sixteen pregnant women who met the inclusion criteria were included in the study. To evaluate whether serum haptoglobin level in maternal blood could be used in early diagnosis of preeclampsia and HELLP syndrome, 49 pregnant women diagnosed with preeclampsia and 13 pregnant women diagnosed with HELLP syndrome were included in the study group, and 54 healthy pregnant women in the control group. The groups were compared regarding maternal serum haptoglobin level, platelet count, ALT, AST, LDH, and uric acid levels. Moreover, the age, obstetric histories, and newborn outcomes of all pregnant women were recorded and compared between groups. The mean haptoglobin values were 0.29 ± 0.23 g/L in the HELLP syndrome group, 1.01 ± 0.52 g/L in the preeclampsia group, and 1.16 ± 0.37 g/L in the control group. The mean haptoglobin result was lower in the HELLP syndrome group compared to the preeclampsia and control groups (p < 0.001). While the differences between HELLP syndrome and the control and preeclampsia groups were statistically significant, no significant difference was determined between the preeclampsia and control groups. There was a significant positive correlation between haptoglobin value with the week of delivery, umbilical cord pH value, and the first and fifth-minute Apgar scores (p < 0.05). It was concluded that haptoglobin values could be used together with other biochemical parameters to diagnose HELLP syndrome and predict newborn outcomes.

Role of Haptoglobin in Protecting the Toxic Effects of Hemoglobin in Various Pathologies

The review presents modern domestic and foreign literature data on the blood plasma protein haptoglobin, its structure, synthesis, function and interaction with hemoglobin. The ability of haptoglobin in interaction with hemoglobin to reduce the toxic effect of the latter is shown. Clinical studies of such interaction in various pathological conditions such as diabetes mellitus, sickle cell anemia, malaria, sepsis, etc. are described. It is noted that the development of new haptoglobin derivatives can contribute to the prevention of hemoglobin toxicity in hemolytic diseases.

Clinical Significance of Serum Haptoglobin and Protein Disulfide-Isomerase A3 in the Screening, Diagnosis, and Staging of Colorectal Cancer.

Objective: This study aims to explore the clinical significance of haptoglobin (HP) and protein disulfide-isomerase A3 (PDIA3) in human serum in the screening, diagnosis and staging of colorectal cancer (CRC), and to provide novel screening approaches featuring high specificity, sensitivity, and accuracy for early screening and diagnosis of clinical colorectal cancer. Methods: 88, 77, and 36 blood specimens were respectively harvested from colorectal cancer patients, colorectal polyp patients, and normal subjects (the health examination) who requested medical assistance from our hospital between Oct2019 and February 2022. The serum contents of HP and PDIA3 in each sample were determined through an enzyme linked immunosorbent assay (ELISA). This step was taken to analyze the differences among different specimen groups in terms of the serum contents of HP and PDIA3, to analyze the relationships between the expression levels of HP and PDIA3 and the pathological characteristics of colorectal cancer, and to explore the critical role of HP and PDIA3 in the screening, diagnosis, and staging of colorectal cancer. Results: Serum contents of HP and PDIA3 were higher in colorectal cancer patients, with statistical differences (p < 0.05), than those in the colonic polyp patients and healthy subjects. Receiver operating characteristic (ROC) curve demonstrated that the cut-offs of HP and PDIA3 serum contents indicating colorectal cancer were 149 ug/ml and 66 ng/ml respectively. The individually and jointly tested AUCs of HP (0.802) and PDIA3 (0.727) were higher than those of serum CEA and CA199, the sensitivity and specificity of HP were 64.8 and 91.2%, the sensitivity and specificity of PDIA3 were 65.9 and 71.7%. Moreover, the contents of HP and PDIA3 increased alongside disease progression, with differences (p < 0.05). Conclusion: Our research indicated that joint testing of HP and PDIA3 was of reference value for progressive stage and reliable biological indicators of colorectal cancer screening.

Role of Haptoglobin as a Marker of Muscular Improvement in Patients with Multiple Sclerosis after Administration of Epigallocatechin Gallate and Increase of Beta-Hydroxybutyrate in the Blood: A Pilot Study.

Here, we report on the role of haptoglobin (Hp), whose expression depends on the synthesis of interleukin 6 (IL-6), related to the pathogenesis of multiple sclerosis (MS), as a possible marker of muscle improvement achieved after treatment with the polyphenol epigallocatechin gallate (EGCG) and an increase in the ketone body beta-hydroxybutyrate (BHB) in the blood. After 4 months of intervention with 27 MS patients, we observed that Hp does not significantly increase, alongside a significant decrease in IL-6 and a significant increase in muscle percentage. At the same time, Hp synthesis is considerably and positively correlated with IL-6 both before and after treatment; while this correlation occurs significantly reversed with muscle percentage before treatment, no correlation is evident after the intervention. These results seem to indicate that Hp could be a marker of muscle status and could be a diagnosis tool after therapeutic intervention in MS patients.

The role of haptoglobin and hemopexin in the prevention of delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage: a review of current literature.

Delayed cerebral ischaemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) is a major cause of mortality and morbidity. The pathophysiology of DCI after aSAH is thought to involve toxic mediators released from lysis of red blood cells within the subarachnoid space, including free haemoglobin and haem. Haptoglobin and hemopexin are endogenously produced acute phase proteins that are involved in the clearance of these toxic mediators. The aim of this review is to investigate the pathophysiological mechanisms involved in DCI and the role of both endogenous as well as exogenously administered haptoglobin and hemopexin in the prevention of DCI.

Role of Haptoglobin in Health and Disease: A Focus on Diabetes.

In Brief Prospective identification of individuals with diabetes who are at greatest risk for developing complications would have considerable public health importance by allowing appropriate resources to be focused on those who would benefit most from aggressive intervention. Haptoglobin (Hp) is an acute-phase protein that is crucial for the elimination of free hemoglobin and the neutralization of oxidative damage. In the past two decades, associations have been made between polymorphisms in Hp and complications arising from diabetes. Individuals with polymorphism in Hp have been shown to have significantly higher risk of developing cardiovascular disease. This review summarizes the current literature on the role of Hp in health and disease, with a focus on diabetes.

Haptoglobin and CCR2 receptor expression in ovarian cancer cells that were exposed to ascitic fluid: Exploring a new role of haptoglobin in the tumoral microenvironment

Haptoglobin (Hp) is an acute-phase protein that is produced by the liver to capture the iron that is present in the blood circulation, thus avoiding its accumulation in the blood. Moreover, Hp has been detected in a wide variety of tissues, in which it performs various functions. In addition, this protein is considered a potential biomarker in many diseases, such as cancer, including ovarian carcinoma; however, its participation in the cancerous processes has not yet been determined. The objective of this work was to demonstrate the expression of Hp and its receptor CCR2 in the ovarian cancer cells and its possible involvement in the process of cell migration through changes in the rearrangement of the actin cytoskeleton using western blot and wound-healing assays and confirming by confocal microscopy. Ovarian cancer cells express both Hp and its receptor CCR2 but only after exposure to ascitic fluid, inducing moderated cell migration. However, when the cells are exposed to exogenous Hp, the expression of CCR2 is induced together with drastic changes in the actin cytoskeleton rearrangement. At the same time, Hp induced cell migration in a much more efficient manner than did ascitic fluid. These effects were blocked when the CCR2 synthetic antagonist RS102895 was used to pretreat the cells. These results suggest that Hp-induced changes in the cell morphology, actin cytoskeleton structure, and migration ability of tumor cells, is possibly “preparing” these cells for the potential induction of the metastatic phenotype.

Expression and clinical significance of haptoglobin in papillary thyroid carcinoma tissue microarray

Objective To explore the role of haptoglobin in papillary thyroid carcinoma by applying tissue microarraies.Methods We constructed the tissue microarraies with 11 papillary thyroid carcinomas,67 benign thyroid nodes and 50 normal thyroid tissues.Immunohistochemical method was applied to detect the expression of haptoglobin in papillary thyroid carcinoma,benign thyroid node and normal thyroid tissues.Results In 112 cases of papillary thyroid carcinomas,the positive expression rate of haptoglobin was 79％.Papillary thyroid carcinoma samples expressed much higher haptoglobin levels than benign thyroid node (12％) and normal thyroids (8％,P ＜0.05).However,there was no statistically significant difference in the haptoglobin expression between benign thyroid node and normal thyroid tissues (P ＞0.05).Conclusion Haptoglobin is closely related with the occurrence of human papillary thyroid carcinoma.Furthermore,it may play an important role in development and evolution of this malignant tumor. Key words: Haptoglobin; Papillary thyroid carcinoma; Tissue microarray

Identification and confirmation of haptoglobin as a potential serum biomarker in hypertrophic cardiomyopathy using proteomic approaches

Introduction. Aiming at identifying biomarkers for hypertrophic cardiomyopathy (HCM), the serum proteome was explored through a two-dimensional gel-based proteomic approach (2D-DIGE) coupled with mass spectrometry and database interrogation.Methods. Serum samples from 20 male HCM patients and their sex- and age-matched controls were cleaned from interfering components. Patients and controls were pooled in five matched groups with the same age, and proteins extracts from each pool were labelled with cyanine dyes. Then, gel images were analysed using a fluorescence scanner and proteins were identified. Tryptic peptides were analysed by capillary reversed-phase liquid chromatography coupled online with tandem mass spectrometry (MS/MS).Results. Four different proteins were observed to be differentially expressed between HCM patients and their matched controls. Of them, decreases in haptoglobin levels were confirmed to be associated with HCM in an independent set of 181 consecutive HCM patients from our monographic clinic and 114 controls with similar age and sex using a nephelometer-based technique. Moreover, a significant negative correlation was observed between haptoglobin and subaortic gradient, thus highlighting the role of haptoglobin in HCM.Conclusion. All these observations point out the utility of the 2D-DIGE proteomic strategy for the identification of serum proteins indicative of the presence of cardiac injury.

Response to ‘Haptoglobin in diagnosis of sepsis’

We appreciate the interest and the insightful comments that Dr Philip made about our article. We regret the omission of reference to his studies in our manuscript; his work on the subject done several decades ago has made a significant contribution to the knowledge of the kinetics and the role of haptoglobin (Hp) in newborns. Our results are in accordance with his findings and contribute with new information particularly concerning the early preterm group, as 14 patients in our study were born at <32 weeks gestational age. However, other researchers have been unable to detect Hp consistently in newborns, regardless of gestational age.1, 2, 3 The establishment of normal Hp values for premature and term newborns continues to be controversial. We hope that our work will contribute to improve the accuracy of neonatal Hp values provided by many clinical laboratories and various reference texts that generally report them at zero or do not provide them at all.4, 5, 6

122-P Role of haptoglobin and its polymorphism in bronchial asthma

122-P Role of haptoglobin and its polymorphism in bronchial asthma

Role of Haptoglobin in Susceptibility of IBD and in Triggering Murine Colitis

Role of Haptoglobin in Susceptibility of IBD and in Triggering Murine Colitis

Haptoglobin inhibits phospholipid transfer protein activity in hyperlipidemic human plasma

BackgroundHaptoglobin is a plasma protein that scavenges haemoglobin during haemolysis. Phospholipid Transfer Protein (PLTP) transfers lipids from Low Density Lipoproteins (LDL) to High Density Lipoproteins (HDL). PLTP is involved in the pathogenesis of atherosclerosis which causes coronary artery disease, the leading cause of death in North America. It has been shown that Apolipoprotein-A1 (Apo-A1) binds and regulates PLTP activity. Haptoglobin can also bind to Apo-A1, affecting the ability of Apo-A1 to induce enzymatic activities. Thus we hypothesize that haptoglobin inhibits PLTP activity. This work tested the effect of Haptoglobin and Apo-A1 addition on PLTP activity in human plasma samples. The results will contribute to our understanding of the role of haptoglobin on modulating reverse cholesterol transport.ResultsWe analyzed the PLTP activity and Apo-A1 and Haptoglobin content in six hyperlipidemic and six normolipidemic plasmas. We found that Apo-A1 levels are proportional to PLTP activity in hyperlipidemic (R2 = 0.66, p < 0.05) but not in normolipidemic human plasma. Haptoglobin levels and PLTP activity are inversely proportional in hyperlipidemic plasmas (R2 = 0.57, p > 0.05). When the PLTP activity was graphed versus the Hp/Apo-A1 ratio in hyperlipidemic plasma there was a significant correlation (R2 = 0.69, p < 0.05) suggesting that PLTP activity is affected by the combined effect of Apo-A1 and haptoglobin. When haptoglobin was added to individual hyperlipidemic plasma samples there was a dose dependent decrease in PLTP activity. In these samples we also found a negative correlation (-0.59, p < 0.05) between PLTP activity and Hp/Apo-A1. When we added an amount of haptoglobin equivalent to 100% of the basal levels, we found a 64 ± 23% decrease (p < 0.05) in PLTP activity compared to basal PLTP activity. We tested the hypothesis that additional Apo-A1 would induce PLTP activity. Interestingly we found a dose dependent decrease in PLTP activity upon Apo-A1 addition. When both Apo-A1 and Hpt were added to the plasma samples there was no further reduction in PLTP activity suggesting that they act through a common pathway.ConclusionThese findings suggest an inhibitory effect of Haptoglobin over PLTP activity in hyperlipidemic plasma that may contribute to the regulation of reverse cholesterol transport.

Role of Haptoglobin in Polycystic Ovary Syndrome (PCOS), Obesity and Disorders of Glucose Tolerance in Premenopausal Women

Background Hp2 alleles of the haptoglobin α–chain polymorphism reduce the anti-oxidant properties and increase the pro-inflammatory actions of this acute-phase protein in a gene-dosage fashion. We hypothesized that the haptoglobin polymorphism might contribute to the increased oxidative stress and low-grade chronic inflammation frequently associated with polycystic ovary syndrome, obesity, and abnormalities of glucose tolerance.Methodology/Principal FindingsSerum haptoglobin and the haptoglobin α–chain polymorphism were determined in 141 patients with polycystic ovary syndrome and 102 non-hyperandrogenic women. Of the whole group of 243 premenopausal women, 117 were obese and 51 showed abnormal glucose tolerance. Although serum haptoglobin concentrations were similar in PCOS patients and controls, the former presented with an increased frequency of Hp2 alleles (62% vs. 52%, P = 0.023). Circulating haptoglobin levels increased with obesity (P<0.001), yet no association was found between obesity and haptoglobin genotypes. No differences were observed in haptoglobin levels or genotype frequencies depending on glucose tolerance. Fifty percent of the variation in serum haptoglobin concentrations was explained by the variability in serum C-reactive protein concentrations, BMI, insulin sensitivity and haptoglobin genotypes.Conclusions/SignificanceSerum haptoglobin concentrations in premenopausal women are largely dependent on the haptoglobin polymorphism and on the presence of obesity, with insulin resistance and chronic inflammation possibly modulating this relationship. The association of polycystic ovary syndrome with Hp2 alleles suggests that the anti-oxidant and anti-inflammatory properties of haptoglobin may be reduced in these patients.

Role of Haptoglobin on the Uptake of Native and β-Chain [Trimesoyl-(Lys82)β-(Lys82)β] Cross-Linked Human Hemoglobins in Isolated Perfused Rat Livers

The role of haptoglobin in liver cell entry of acellular native hemoglobin, and cross-linked human hemoglobin, a potentially useful oxygen-carrier alternative in transfusion medicine, was examined in the recirculating, perfused rat liver preparation. Doses of tritiated native human or beta-chain [trimesoyl-(Lys82)beta-(Lys82)beta] cross-linked human hemoglobin were preincubated with haptoglobin-containing rat plasma or Krebs Henseleit bicarbonate buffer for 30 min and used for perfusion. Concentrations (dpm/ml) in reservoir, before and after separation of the hemoglobins and metabolites by gel filtration fast protein liquid chromatography column chromatography, were similar, showing mostly the presence of intact hemoglobin. Each hemoglobin species underwent a rapid distribution phase, followed by a protracted elimination phase. The radioactivity in bile at 3 h consisted of low molecular weight metabolites, and cumulative excretion was slightly higher when rat plasma was present: for native hemoglobin, 7.1 +/- 1.6% versus 9.2 +/- 2.1% dose; for cross-linked hemoglobin, 5.0 +/- 1.7% versus 7.2 +/- 0.8% dose. Data fit to a two-compartment model and physiologically based model revealed a significantly faster influx clearance (CL(influx)) over the metabolic intrinsic clearance (CL(int, met)). The ratios of CL(influx)/CL(int, met) were 125 and 535 for native hemoglobin in the absence and presence of rat haptoglobin, respectively, according to compartmental analyses; the ratios were 25 and 53, respectively, according to physiological modeling. The corresponding ratios for cross-linked hemoglobin in the absence and presence of rat haptoglobin were 55 and 81, respectively, and 24 and 70 for compartmental and physiological modeling. Although haptoglobin enhanced the hepatic internalization of the hemoglobins, the impact on the net clearance was lessened since degradation was the rate-limiting step.

Haptoglobin modifies the hemochromatosis phenotype in mice

AbstractClassic hereditary hemochromatosis (HH) is a common genetic disorder of iron metabolism caused by a mutation in the HFE gene. Whereas the prevalence of the mutation is very high, the clinical penetrance of the disease is low, suggesting that the HFE mutation is a necessary but not sufficient cause of clinical HH. Several candidate modifier genes have been proposed in mice and humans, including haptoglobin. Haptoglobin is the plasma protein with the highest binding affinity for hemoglobin. It delivers free plasma hemoglobin to the reticuloendothelial system, thus reducing loss of hemoglobin through the glomeruli and allowing heme-iron recycling. To gain insight into the role of haptoglobin as a modifier gene in HH, we used Hfe and haptoglobin double-null mice. Here, we show that Hfe and haptoglobin compound mutant mice accumulate significantly less hepatic iron than Hfe-null mice, thus demonstrating that haptoglobin-mediated heme-iron recovery may contribute significantly to iron loading in HH. (Blood. 2005;105:3353-3355)

A Study on the Role of Haptoglobin in Haemolytic Disease of the Newborn

A Study on the Role of Haptoglobin in Haemolytic Disease of the Newborn