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MPO and Its Role in Cancer, Cardiovascular and Neurological Disorders: An Update

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02 September 2024

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03 September 2024

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Abstract
Myeloperoxidase (MPO) is an enzyme that contains a heme group, found mostly in neutrophils and in small amounts in monocytes and plays a major role in their anti-microbial activity. However, excessive levels of MPO have been linked to various disorders and identified as a major cause of tissue destruction. Inhibiting its activity can reduce the severity and extent of tissue damage. Over activity of MPO during chronic inflammation has been shown to be involved in tumorigenesis by inducing a hyper-mutagenic environment through oxidant interaction with DNA, causing DNA modification. Vascular endothelium is one of the most important targets of MPO and high levels have been associated with increased rates of cardiomyopathy, ischemic stroke, heart failure, myocardial infarction, and atrial fibrillation. Therefore, it may be considered a therapeutic target in the treatment of cardiovascular disorders. MPO also participates in the pathogenesis of neurodegenerative diseases. For example, an increase in MPO levels has been observed in the brain tissue of patients with Alzheimer's, Multiple sclerosis (MS), and Parkinson's diseases. In Alzheimer's disease, active MPO is mostly found in the location of beta amyloids and microglia. Therefore, targeting MPO may be a potential treatment and prevention strategy for neurological disorders. This review will discuss MPO's physiological and pathological role in cancer, cardiovascular, and neurological disorders.
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Subject: Biology and Life Sciences  -   Biology and Biotechnology

Introduction:

Neutrophils

Neutrophils, which are one of the shortest-lived cells of mammals, are the most prevalent leukocyte population in the circulation. These cells are among cells with terminal differentiation and limited transcriptional activity continuously produced by the bone marrow[1,2]. Despite their short life, neutrophils play multiple roles in the immunogenic and inflammatory processes of the body. In addition to being one of the first lines of defense against various infections, due to having active oxygen species and numerous enzymes, they can destroy the pathogen as soon as the microbial species enters. Among other unique actions of neutrophils, the protrusion of their genomic DNA in the form of a neutrophil extracellular trap (NET) can be mentioned. Materials related to NETs are usually rich in nuclear histones due to their production from the nucleus and also, various types of granular proteins, cytosolic proteins, and most importantly antimicrobial proteins such as MPO can be observed in their structure. Of course, considering that the general composition of NETs can change depending on the type of stimulus, in some cases, they may originate from mitochondria, in which case they will lack histones. NETs are released to decrease the level of diffusion of pathogenic microorganisms and also help to destroy them. But, the point is that, in the case of unprogrammed immune responses, usually the irregular production of NETs can occur which leads to inflammation increment and damage of host cells. Neutrophils use different methods to play their role in inflammation and immunogenesis, the most important of which are enzymatic processes including the production of reactive oxygen species by nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase, secretion of granule-derived MPO, and hydrolytic enzyme production[1,3,4].Indeed, neutrophils are multifunctional cells that have broad capabilities in a wide range of infectious and non-infectious disease conditions.

Myeloperoxidase (MPO)

MPO is a peroxidase enzyme containing a heme group, which is found in neutrophils and small amounts in monocytes. In early studies, MPO was proved to be an oxygen-dependent antimicrobial system in phagocytes, especially neutrophils [3,5,6]. During the process of myelopoiesis within the bone marrow, there is an active synthesis of myeloperoxidase in promyelocytes and promonocytes. However, in myeloid cells that have reached full differentiation, the synthesis of MPO typically ceases [7]. Neutrophils have 3 types of granules, the second and third types are free of peroxidase despite having different proteins but the granules of the first type are peroxidase positive due to the high amount of MPO, although these granules also contain many proteolytic enzymes that bind to the negatively charged proteoglycans inside the granules and according to the acidic pH inside the granules, these enzymes remain inactive[7,8].
The biosynthesis of MPO includes very complex processes during which after the production of pre-MPO as the first translation product in endoplasmic reticulum, glycosylation of six asparagine causes its conversion to inactive apo-pro-MPO, which is converted to active pro-MPO by adding heme. Then, in the secretory pathway from the endoplasmic reticulum, proteolytic processes and dimerization take place and cause the appearance of mature MPO, which is observed in neutrophilic granules (Figure 2)[9]. MPO, as an important part of NETs, is always present in cases where neutrophils flow to the site of inflammation to phagocytose pathogenic microorganisms, and by creating an alkaline environment inside the phagosome, it creates a stable environment for killing germs. Also, after the completion of the phagocytosis process, MPO with its peroxidation function helps to protect the surrounding tissues against substances caused by proteolysis[10]. Duo to prominent role of MPO in several disorders, its measurement method has a vital importance. Common protocol of measuring is spectrophotometric method which is so functional and helpful. Spectrophotometric assay is based on the oxidizing activity of o-diazinidine in an H2o2 rich environment which is a simple, low cost and sensitive method[11,12]. However, recently, a novel fluorometric method has been introduced. This colorimetric technique measures MPO activity specifically and is related to H2O2-dependant oxidation process of Thiamin. Distinctive feature of this protocol is an exceptional sensitivity, accuracy and specificity that makes it a dependable method in future studies[13].

MPO and Immune System

Various studies have proven that MPO takes over a major part of the microbicidal activity of immune cells, including neutrophils and monocytes, which takes place through the production of HOCl. During the inflammatory process, the metabolism of nitric oxide in neutrophils occurs at a high rate, which leads to the production of a high amount of Nitrogen Dioxide (NO2). These along with halide ions, create a suitable substrate for the peroxidase activity of MPO, which in vitro studies also indicate that this complex can be a powerful anti-microbial system. If the amount of halides is significantly reduced, the germicidal effect of neutrophils decreases, but in neutrophils without MPO, the reduction of halides does not affect the power of neutrophils. Of course, it is worth mentioning that the presence of Hydrogen peroxide (H2O2) is necessary for the proper functioning of this system so that in the case of catalase enzyme and the reduction of this substance, the phagocytic activity of neutrophils is reduced. Of course, this fact is evident that excessive production of oxidants is associated with a series of diseases characterized by inflammation. For example, it has been observed that HOCl leads to an increase in the production of tumor necrosis factor alpha (TNF-α) by altering the function of immune cells [14,15,16].
Modulation of inflammatory responses is not limited here, and even other activities of lymphocytes, including reduction of mitogenic proliferation and cytotoxic effects, are affected by MPO-derived oxidants. In addition, MPO is also related to the adhesion and communication between other cells and leukocytes, but this can be changed by using monoclonal antibodies. Moreover, in vitro studies have shown that the MPO binding to CD11b/CD18 integrin causes delayed apoptosis of neutrophils and prolonged inflammatory responses by induction of extracellular signal-activated kinase and Akt signaling. Interestingly, in experimental models of diseases related to acute inflammation, such as ischemic reperfusion, the reduction of MPO results in a drastic reduction in clinical and pathological symptoms, including neutrophil accumulation. Collectively, overexpression of MPO whether through the overproduction of oxidants or by functional modulation of immune cells can contribute to the development of cancers, tissue damage, and prolongation of inflammatory responses [7,17,18]?

MPO in Diseases

MPO enzyme plays an important role in many physiological and pathological processes (Table 1), some of which are discussed below: [14,19,20,21,22,23,24,25,26,27,28]

MPO and Cancer

Among the various diversity in the microenvironment surrounding the tumor, one of the most important ones is neutrophils, which seems to play a significant role in tumor survival or destruction. MPO has received much attention as one of the enzymes secreted by neutrophils. Although the exact role of MPO in tumor pathophysiology has not yet been determined, most studies have proven its enhancing effect on tumor occurrence and growth. This role can be based on the production of oxidants derived from MPO, which can lead to oxidation and mutation of the DNA molecule[38]. There is cumulative evidence indicate that MPO-derived oxygen radical can impair the proper function of natural killer cells which play a significant role in the innate host defense and immune surveillance by mediating antibody-dependent and -independent cytotoxicity towards tumors and viral-infected cells[39]. Accordingly, over-expression of MPO is expected to elevate risks of tumorigenesis through suppression of natural killer (NK) cells involved in immune surveillance. Also, the observation of neutrophilia is one of the signs of difficult treatment in patients with lung cancer. The MPO-derived active species cause the formation of free radicals centered on DNA and ultimately DNA oxidation. In addition, MPO plays an effective role in the occurrence and growth of lung tumors by converting environmental pollutants and procarcinogenic substances into carcinogens. Some studies also show the role of MPO in inhibiting damaged DNA repair mechanisms [14,40].Over activity of MPO during chronic inflammations has been also demonstrated to be involved in tumorigenesis through induction of a hyper-mutagenic environment following interaction of MPO-derived oxidants with DNA resulting in DNA modification[41].
A study on the role of MPO in the incidence and treatment of colorectal cancer has shown that the amount of MPO in these patients has increased significantly and has a direct relationship with the degree of malignancy and cancer progression. Also, by confirming the correlation of MPO level with the number of peripheral neutrophils, this study has proven that the high level of neutrophils directly reduces the survival rate of patients. The high level of MPO can be considered a poor prognosis factor in patients with colorectal cancer [29,42]. Investigating the association between neutrophil infiltration and incidence of colitis-associated colorectal cancer revealed that higher levels of MPO and neutrophil infiltration boost the switching of ulcerative colitis to colorectal cancer [43]. Examining the effects of MPO in mice breast cancer has also shown that the stimulation of MPO and eosinophil peroxidase increases the size and number of breast tumors, and it also has a direct effect on increasing the transcription of metastatic genes and leads to increment in occurrence of metastasis and level of angiogenesis[44]. Also, the presence of NETs (especially MPO) in the microenvironment of high-grade serous ovarian cancer (HGSOC) contributed to the progression of disease in a way that NETosis is supposed to play a vital role in the occurrence of metastasis in the early stages of HGSOC. Hence, MPO could be used as a precise biomarker for ovarian cancer diagnosis [45,46]. During a study on the lung cancer of mice, it was observed that if a MPO inhibitor, N-acetyl lysyltyrosylcysteine amide, (KYC) is used, a reduction in the incidence of lung tumors occurs. Also, this study proved that in MPO-deficient mice, lung carcinoma tumor growth was significantly lower than in other groups[30]. An evaluation of the level of MPO, paraoxonase, and High-density lipoprotein (HDL) levels in acute myeloid leukemia confirmed the vital role of MPO, inflammation, and oxidative stress in the pathogenesis of this disease and these parameters can be considered as a prediction of response to chemotherapy[47].
Among the mechanisms of anti-tumor activity of neutrophils, we can mention the anti-oncogenic role of HOCL produced by MPO, which induces cancer cell death. This function is due to the production of types of superoxide anion from tumor cells, which in reaction with HOCL leads to the production of hydroxyl radicals that enhance apoptosis. But tumor cells prevent this process by producing a series of membrane catalases. Here, it is possible to prevent the inhibition of the apoptosis process and even strengthen it by using catalase inhibitors. Among the other mechanisms of MPO in increasing the proliferation rate of cancer cells and the occurrence of malignancy, we can mention the oxidation of cell matrix components due to the oxidants derived from MPO, which causes a decrease in adhesion, and ultimately changes in the proliferation rate of endothelial cells and cell migration[14,29,41,48,49].

MPO and Cardiovascular Diseases

Vascular endothelium is one of the most important targets of MPO and MPO-derived oxidants. For example, in atherosclerosis, an increase in MPO levels has been identified as one of the most important causes of tissue destruction, and with the use of antibodies against HOCl-LDL, the severity and extent of tissue damage are reduced[23,50].Some studies have shown the relationship between increased levels of MPO and disruption of vascular endothelial function, for example, oxidants derived from MPO can cause damage to vascular endothelium by reducing the bioavailability of nitric oxide (NO), which is the result of changes in the expression of the relevant gene or the change in the availability of the substrate for the synthesis of endothelial NO[5]. Furthermore, the vascular injuries caused by MPO can also arise from the facilitation of atherosclerotic plaque development in foamy macrophages, the instability of atherosclerotic plaques due to the activation of matrix metalloproteinase (MMP), and the interactions of P-selectin that induce local occlusive thrombosis [51]. Effect on intracellular signaling cascades is one of the other ways of MPO function for endothelial damage and inflammation exacerbation. MPO, by activating the Rho kinase signaling pathway, can disrupt the dilation of blood vessels and increase the pressure of the right ventricle, which causes an increase in arterial blood pressure, or MPO, by activating calpains, increases the expression of the adhesion molecules of blood vessels and as a result increases the adhesion of leukocytes to the endothelium. The increase in the level of HOCL in the sub-endothelium due to the increase in the amount of MPO and the stimulation of apoptosis of endothelial cells causes the instability of the formed plaques and the occurrence of thrombogenesis [52].
In addition, modification of low-density lipoproteins (LDL) and HDL by MPO and its derivative oxidants increases the proatherogenic function of LDL and decreases the cardioprotective effect of HDL, both of which contribute to the occurrence of atherosclerosis. LDL modified by HOCl causes the accumulation of cholesterol and sterols due to recognition by macrophages. In addition, damage to the vascular endothelium may occur due to increased adhesion of macrophages to this type of LDL and decreased production of NO. The binding of MPO to Apo lipoprotein A1 disrupts HDL function in two ways. This connection disrupts the acceptance of this Apo lipoprotein, and on the other hand, it promotes the pro-inflammatory profile of the endothelial vessels. Also, the presence of HDL modified by MPO reduces the activity of vascular smooth muscle cells (VSMC), which leads to the instability of the plaques formed in the vessels[53]. Furthermore, it has been observed that the presence of MPO-derived oxidants disrupts the anti-apoptotic activity of HDL and reduces the protective activity of HDL in atherosclerotic plaques [3,23,54].
Today, to diagnose acute coronary syndrome, in addition to checking cardiac troponin, the level of MPO is also measured in patients presenting with angina symptoms, because it has been observed that in some cases, even with the presence of negative cardiac troponin, a high level of MPO indicates the occurrence of this disease[14,55].In the pathogenesis of atrial fibrillation (AF), elevated levels of MPO expression occurred and both MPO and neutrophil levels are much higher in patients with persistent AF and this makes measurement a good criterion for predicting AF[56]. Also, the increased level of MPO played an important role in a switch of AF phenotype and relapse after catheter ablation[57]. Generally, high levels of MPO contributed to the increased rate of cardiomyopathy, ischemic stroke, heart failure (HF), Myocardial infarction (MI), Ventricular Tachycardia (VT) and AF [58,59,60,61,62,63,64]. So it can be considered a therapeutic target in the treatment of cardiovascular disorders such as coronary artery diseases and future studies should specify whether the immunoeffective role of MPO overweigh the atherogenic effect of this biomarker [65].
Previous studies about the effects of different drugs on cardiovascular diseases demonstrated that a decrease in the level of MPO is associated with the protective effects. We have shown in our previous studies, that metformin administration in myocardial infarction, in addition to reducing fibrosis and cardiac remodeling, causes a significant decrease in MPO and TNF-α levels in rats[66]. Also, regarding the protective effects of memantine in heart failure in rats, in addition to reducing cardiac remodeling and lipid peroxidation, another mechanism of action of memantine was the reduction of MPO[67].Other experimental studies, investigating the effects of different plant extracts on myocardial infarction also showed the protective mechanisms of Arum orientale and Marrubiumvulgareby reducing the level of inflammation, lipid peroxidation, infiltration of neutrophils and the level of MPO[68,69].Administration of memantine as a protective agent in myocardial infarction in rats, also, showed that this protective effect contributed to the reduction in the level of MPO, malondialdehyde, and TNF-α [70].

MPO and Nervous System

Various studies emphasize the role of MPO in the pathogenesis of neurodegenerative diseases, which is mostly through the oxidative damage of MPO-derived oxidants. This oxidative damage includes damage to all cellular components such as proteins, carbohydrates, lipids, and nucleic acids, which ultimately occurs due to excessive production of free radicals, cell disorder, and apoptosis[71,72]. For example, an increase in the level of MPO and the occurrence of lipid peroxidation in the brain tissue of patients with Alzheimer's, MS, and Parkinson's diseases have been observed, and in Alzheimer's disease, the presence of active MPO is mostly seen in the location of beta amyloids and microglia[73,74]. Furthermore, in the lesional tissue of patients with MS, which is considered a degenerative inflammatory disease, protein and mRNA expression of MPO has been observed in microglia and macrophages[75]. Although there are conflicting data about the role of MPO in MS, the supportive role of MPO is in the occurrence of disturbance in the normal activity of the immune system[76,77].It has been observed that the severity of neuronal damage is associated with the expression of the MPO gene and higher levels of inflammation and oxidative stress in MS[78].Among other diseases in which the role of MPO in its pathogenesis has been established is Parkinson's disease, in which increased expression of MPO is observed in the glial cells of dopaminergic neurons, which indicates the role of MPO and its derived oxidants in Parkinson's neurotoxic process[37,79].Elevated levels of NOX4 (one of the reactive oxidative species) in cooperation with MPO are the vital components in progression of neuroinflammation during Parkinson disease[80].Also, a recent study about depression showed that the expression of MPO gene in both mRNA and protein levels elevated significantly in people with depressive disorders revealing the important role of MPO in regulation of cognitive processes[81].
The previous studies of our research team with different drugs that have shown neuroprotective effects of cerebral ischemia/reperfusion all indicate the reduction of MPO activity as one of the mechanisms involved in these protective effects. For example, metformin by decreasing the levels of MPO, malondialdehyde, and leukocyte infiltration reduces cerebral ischemia /reperfusion-induced injuries[82].A similar study demonstrated that the neuroprotective effect of canagliflozin in cerebral cortex injury is associated with lower levels of cortical MPO, malondialdehyde, TNF-alpha, and Interleukin-6[83]. A recent study on the effects of diltiazem and metoprolol in cerebral ischemia-reperfusion injuries also showed that the use of these two drugs alone or in combination, in addition to reducing the infarct size, also caused a significant reduction in MPO levels[84].The administration of bisoprolol and vitamin E alone and in combination, and also in another study hydroxychloroquine, demonstrated protective effects via a significant decrease in the amount of MPO and Malodialdehyde (MDA), which even protected the memory and learning ability of mice[85,86]. Furthermore, a clinical study about rupturing cerebral aneurysms, revealed that the MPO level was higher in tissues with rupture in comparison to non-ruptured ones, which demonstrates the association of high levels of oxidative stress and inflammation with rupturing cerebral aneurysms [87]. Even, it proved that lower levels of MPO in stroke are along with a decreased level of inflammation and oxidative brain damage and elevated level of cellular protection[88,89].It has also reported that inhibition the enzyme form of MPO increased the neurogenesis and cell proliferation after ischemic stroke[90]So, these results lead us to consider MPO as a treatment and prevention target in stroke[91]. Even more, a recent study showed that serum lipoprotein-associated phospholipase A2 (Lp-PLA2) combined with MPO could be a valuable predictor of the occurrence of cerebral infarction induced by atherosclerosis and this confirmed the diagnostic value of MPO in stroke-related diseases [92].

MPO Inhibition

Considering the important role of MPO in causing and aggravating inflammation, various studies have been conducted to investigate methods to modulate MPO activity to treat various diseases. Among these methods, the use of MPO inhibitors, limiting substrate availability, and increasing H2O2 removal can be mentioned [93].
Due to the high availability of H2O2 inside the body, if its amount is decreased by enzymes such as peroxiredoxins and catalases, the production of free radicals derived from MPO is reduced. It is also possible to decrease H2O2 levels by inhibiting NADPH oxidase, which plays a role in converting O2 to superoxide anion. In addition, replacing other substrates such as NO2 and Thiocyanate (SCN) can inhibit the production of HOCl by MPO, which results in weaker oxidants with lower performance. Even in mice prone to atherosclerosis, in which high expression of MPO is observed, replacing SCN leads to a significant reduction of plaques and MPO inhibition is one of the new methods in this regard[22,93].
Various non-specific inhibitors such as various drugs, relaxants, antioxidants, and natural products such as flavonoids can act as substrates of peroxidases and remove MPO from the halogenation cycle. For example, it has been proven that the use of quercetin (a flavonoid) can reduce vascular endothelial damage caused by MPO-mediated HOCL[94]. Therewith, the use of cyclic nitroxides as enzyme substrates in a myocardial inflammation model can significantly reduce HOCl production, or the use of peptide N-acetyl lysyltyrosyl cysteine amide (KYC) as a reversible inhibitor of MPO leads to produce lower amounts of MPO-derived HOCl [95,96,97].
Furthermore, some non-selective inhibitors prevent its activity by binding to MPO, among which ceruloplasmin containing copper in plasma or heparin, which is considered an anticoagulant, by electrostatically adhering to MPO, can be mentioned. It reduces its activity and causes less plaque transfer in patients with stable coronary artery disease[98].Some other compounds act competitively as HOCl targets, including taurine. If the concentration of taurine in neutrophils increases, the infiltration of macrophages and the fragmentation of elastin decrease, which ultimately leads to a reduction in the expression of MPO in patients with abdominal aortic aneurysm. Similarly, some compounds containing selenium react quickly with MPO-derived oxidants and produce selenoxides that are easily recycled by cellular regenerators and antioxidant enzymes[99,100].
Suicide substrates are among the most effective and specific MPO inhibitors. For example, hydrazines and hydrazides act by irreversible degradation of MPO, which, of course, are highly toxic and are rarely used in vivo. For example, 4-aminobenzoic acid hydrazide inhibits MPO activity by producing iron-MPO complexes. It disrupts and reduces inflammation and vascular stress and reduces infarct size in stroke models, but on the other hand, it also destroysheme groups. Thioxanthenes are another group of compounds that prevent the production of HOCl by using covalent and irreversible binding to MPO and changing it. These compounds have very high reaction power and act quickly. Recently, AZM 198, which is one of the derivatives of these compounds, has been used for atherosclerosis, which has completely inhibited the MPO function and reduced plaque instability in atherosclerosis. Also, this compound can be effective in increasing pulmonary artery blood pressure due to its ability to reduce the activation of Rhokinase related to MPO[101,102,103].At biomarker level, also, administration of AZD4831 (MPO inhibitor) caused a reduction in the progression of heart failure with preserved ejection fraction (HFpEF) [104]. Even in tumor therapy, it has been observed that inhibition of MPO is an effective way to reduce the resistance of patients to immune-check point therapies and it can be so beneficial in cancer treatment [105]. A better understanding of MPO inhibitory mechanisms can lead us to design new drugs to reduce inflammation and thus moderate the progress of inflammation-related diseases such as rheumatoid arthritis and chronic obstructive pulmonary disease[106].

Concluding remarks

MPO is a peroxidase enzyme containing a heme group, which is found in neutrophils and small amounts in monocytes and takes over a major part in their anti-microbicidal activity. High levels of MPO have been identified as one of the most important causes of tissue destruction, and its inhibition reduces the severity and extent of tissue damage. Over activity of MPO contributes to the development and progression of cancer. Also, high levels of MPO contributed to the increased rate of cardiomyopathy, ischemic stroke, HF, MI, and AF. So it can be considered a therapeutic target in the treatment of cardiovascular disorders.
MPO also participates in the pathogenesis of neurodegenerative diseases. For example, an increase in the level of MPO in the brain tissue of patients with Alzheimer's, MS, and Parkinson's diseases has been observed, and these results lead us to consider MPO as a treatment and prevention target for neurological disorders. Therefore, it is suggested that the role of MPO as a biomarker and a therapeutic target should be given more attention.

CRediT authorship contribution statement

Literature search, preparing the draft of the manuscript: KJ; conceptualization, study design, supervision, literature search, manuscript revision: HS. Both authors read and approved the final manuscript.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Declaration of competing interest

The authors declare that there are no conflicts of interest.

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Preprints 116987 g001
Figure 2. Overview of MPO biosynthesis[9].
Figure 2. Overview of MPO biosynthesis[9].
Preprints 116987 g001
Table 1. Summary of the pathological or protective role of MPO in various disorders.
Table 1. Summary of the pathological or protective role of MPO in various disorders.
Diseases Results Pathological/Protective Role
Colon Cancer High levels of MPO was observed in CRC tumors that can be considered as worse survival factor in patients [29]. Pathological Role
Breast Cancer Penetration of MPO-positive cells is a new factor for improving survival of patients with breast cancer [20] Protective Role
Lung Cancer Inhibition of MPO leads to reducing size and number of lung tumors and can be used as a protection agent of lung cancer [30] Pathological Role
Pancreatic Cancer Increasing levels of NETs (such as MPO) are significantly related to tumor progression and malignancy of Pancreatic ductal adenocarcinoma [31] Pathological role
Arthrosclerosis MPO contributes to arteriosclerosis by disrupting the function of endothelial cells, oxidation of LDL, and a high level of MPO is observed in all lesions of this disease [32]. Pathological Role
Myocardial Infarction Reduced level of MPO and neutrophils is significantly contributed to decreased amount of myocardial infarction injury [33] Pathological Role
Heart Failure Irreversible inhibition of MPO leads to reduced rate of heart failure injuries and also improving quality of life in patients with heart failure [34] Pathological Role
Alzheimer Disease The increase in the adhesion of neutrophils and the amount of MPO caused by neutrophils causes vascular oxidative stress and can be one of the therapeutic goals of Alzheimer's disease [35]. Pathological Role
Multiple Sclerosis Patients with multiple sclerosis have shown low serum levels of MPO, and low levels of MPO play an important role in the pathogenesis of this disease [36]. Protective Role
Parkinson Disease High levels of MPO is observed in some brain areas related to this disease (such as putamen, caudate nucleus, and substantianigra) [37] Pathological Role
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