Overview of Therapeutic Effects of Statins on Inflammatory Diseases Through Regulating Adhesive Molecules

2020 ◽  
Vol 15 (7) ◽  
pp. 614-622
Author(s):  
Yibin Meng ◽  
Youhan Wang ◽  
Yibing li ◽  
Song Chon ◽  
Dingjun Hao
Keyword(s):  
Adhesion Molecules ◽  
Cholesterol Metabolism ◽  
Inflammatory Diseases ◽  
Therapeutic Effects ◽  
Regulatory Effect ◽  
Competitive Inhibitors ◽  
Intercellular Adhesion Molecules ◽  
Adhesive Molecules ◽  
Rate Limiting

Simvastatin, lovastatin, rosuvastatin, pravastatin and cerivastatin belong to the statin family, which are competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A. As the rate-limiting enzyme in the pathway of cholesterol metabolism, statins are classically prescribed to patients as lipidlowering agents. However, statins also possess several extra bioactivities, including anti-inflammatory, antiviral and anti-tumor. Interestingly, the most essential mechanism of these activities is that statins could regulate the expression of cell adhesion molecules (CAMs), especially, targeting lymphocytes function-associated molecules (LFA)-1, macrophage (Mac)-1 and intercellular adhesion molecules (ICAM)-1. Therefore, in this paper, we discussed the regulatory effect of statins on CAMs among different diseases. In addition, we provided speculation for the role of statins in treating orthopedic disease.

scholarly journals Deficient CD40-TRAF6 signaling in leukocytes prevents atherosclerosis by skewing the immune response toward an antiinflammatory profile

2010 ◽  
Vol 207 (2) ◽  
pp. 391-404 ◽  
Author(s):  
Esther Lutgens ◽  
Dirk Lievens ◽  
Linda Beckers ◽  
Erwin Wijnands ◽  
Oliver Soehnlein ◽  
...  
Keyword(s):  
Immune Responses ◽  
Inflammatory Diseases ◽  
Tumor Necrosis Factor Receptor ◽  
Cd40 Ligand ◽  
Therapeutic Effects ◽  
Signaling Axis ◽  
Plaque Phenotype ◽  
Necrosis Factor

The CD40–CD40 ligand (CD40L) signaling axis plays an important role in immunological pathways. Consequently, this dyad is involved in chronic inflammatory diseases, including atherosclerosis. Inhibition of CD40L in apolipoprotein E (Apoe)–deficient (Apoe−/−) mice not only reduced atherosclerosis but also conferred a clinically favorable plaque phenotype that was low in inflammation and high in fibrosis. Blockade of CD40L may not be therapeutically feasible, as long-term inhibition will compromise systemic immune responses. Conceivably, more targeted intervention strategies in CD40 signaling will have less deleterious side effects. We report that deficiency in hematopoietic CD40 reduces atherosclerosis and induces features of plaque stability. To elucidate the role of CD40–tumor necrosis factor receptor-associated factor (TRAF) signaling in atherosclerosis, we examined disease progression in mice deficient in CD40 and its associated signaling intermediates. Absence of CD40-TRAF6 but not CD40-TRAF2/3/5 signaling abolishes atherosclerosis and confers plaque fibrosis in Apoe−/− mice. Mice with defective CD40-TRAF6 signaling display a reduced blood count of Ly6Chigh monocytes, an impaired recruitment of Ly6C+ monocytes to the arterial wall, and polarization of macrophages toward an antiinflammatory regulatory M2 signature. These data unveil a role for CD40–TRAF6, but not CD40–TRAF2/3/5, interactions in atherosclerosis and establish that targeting specific components of the CD40–CD40L pathway harbors the potential to achieve therapeutic effects in atherosclerosis.

scholarly journals Role of intercellular adhesion molecules and antibodies to oxidized LDL in pathogenesis of cardiovascular diseases under mercury exposure

2020 ◽  
Vol 99 (10) ◽  
pp. 1120-1126
Author(s):  
Olga V. Naumova ◽  
Irina V. Kudaeva ◽  
Lyudmila B. Masnavieva ◽  
Olga A. Dyakovich
Keyword(s):  
Cardiovascular Diseases ◽  
Adhesion Molecules ◽  
Oxidized Ldl ◽  
Intercellular Adhesion ◽  
Cardiovascular Pathology ◽  
Mercury Intoxication ◽  
Intercellular Adhesion Molecules ◽  
Chronic Mercury Intoxication

Introduction. Exposure to mercury and its compounds can be a risk factor for the development of cardiovascular diseases. The aim of the study is to investigate the levels of antibodies to oxidized LDL, intercellular adhesion molecules sICAM-1, sVCAM-1, and VEGF in individuals exposed to mercury. Material and Methods. A cross-sectional examination was carried out using biochemical methods in persons who have come into contact with metallic mercury with a work experience of more than five years, persons with a first established diagnosis of chronic mercury intoxication, and patients with chronic mercury intoxication in the long-term postexposure period. Results. In persons exposed to mercury with concomitant cardiovascular diseases, the level of sVCAM-1 differed depending on the presence/absence of intoxication and acquired maximum values in its long-term period, while the concentrations of sICAM-1 and antibodies to oxidized LDL did not differ significantly. In the groups without cardiovascular pathology exposed to mercury, the concentration of sVCAM-1 was higher in patients with intoxication, and sICAM-1 was 1.5-2 times lower when compared with experienced individuals, the level of antibodies to oxidized LDL was maximum in the presence of intoxication in its initial period. Discussion. The progression of chronic mercury intoxication is accompanied by an increase in the level of sVCAM-1, and a gradual decrease in the content of sICAM-1 to reference values. Trained workers were found to have elevated sICAM-1 levels. Conclusion. The role of antibodies to oxidized LDL, intercellular adhesion molecules is their multidirectional participation in the mechanisms that inhibit or contribute to the formation of cardiovascular pathology in individuals exposed to mercury.

scholarly journals Aberrant Cholesterol Metabolism in Ovarian Cancer: Identification of Novel Therapeutic Targets

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiangnan He ◽  
Michelle K.Y. Siu ◽  
Hextan Y. S. Ngan ◽  
Karen K. L. Chan
Keyword(s):  
Ovarian Cancer ◽  
Mammalian Cells ◽  
Cholesterol Metabolism ◽  
Cholesterol Biosynthesis ◽  
Therapeutic Targets ◽  
Multiple Cancer ◽  
Cancer Types ◽  
Characteristic Features ◽  
Rate Limiting

Cholesterol is an essential substance in mammalian cells, and cholesterol metabolism plays crucial roles in multiple biological functions. Dysregulated cholesterol metabolism is a metabolic hallmark in several cancers, beyond the Warburg effect. Reprogrammed cholesterol metabolism has been reported to enhance tumorigenesis, metastasis and chemoresistance in multiple cancer types, including ovarian cancer. Ovarian cancer is one of the most aggressive malignancies worldwide. Alterations in metabolic pathways are characteristic features of ovarian cancer; however, the specific role of cholesterol metabolism remains to be established. In this report, we provide an overview of the key proteins involved in cholesterol metabolism in ovarian cancer, including the rate-limiting enzymes in cholesterol biosynthesis, and the proteins involved in cholesterol uptake, storage and trafficking. Also, we review the roles of cholesterol and its derivatives in ovarian cancer and the tumor microenvironment, and discuss promising related therapeutic targets for ovarian cancer.

DETERMINATION OF CYTOKINES AND ADHESION MOLECULES IN ELDERLY AND SENILE PATIENTS WITH AORTIC VALVE CALCIFICATION

2020 ◽  
pp. 107-112
Author(s):  
Н. А. Михеева ◽  
Н. И. Гуляев ◽  
И. Б. Олексюк ◽  
К. Л. Козлов ◽  
М. А. Соловьев ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Adhesion Molecules ◽  
Control Group ◽  
Aortic Valve Calcification ◽  
Direct Role ◽  
Valve Calcification ◽  
Initial Stage ◽  
Intercellular Adhesion Molecules

Выполнено лабораторное исследование цитокинового профиля и содержания молекул межклеточной адгезии у 38 пациентов с начальными признаками кальциноза аортальных полулуний. Определено, что содержание IL -6 и IL -8 имело достоверно более высокие значения по сравнению с контрольной группой, что свидетельствует о непосредственной роли неспецифического хронического воспаления при развитии кальцинирующего поражения клапана аорты. Также было выявлено значимо более низкое содержание sE -селектина, что может говорить об отсутствии активации молекул адгезии на начальном этапе формирования кальциноза клапана аорты. Необходимо дальнейшее изучение динамики содержания sE -и sP -селектинов в процессе развития ускорения кровотока на аортальном клапане и формировании стеноза. A laboratory study of the cytokine profile and the content of the intercellular adhesion molecules was performed in 38 patients with initial signs of aortic hemilunus calcification. It has been determined that the content of IL -6 and IL -8 had significantly higher values compared with the control group, which indicates the direct role of nonspecific chronic inflammation in the development of calcifying aortic valve damage. A significantly lower content of sE -selectin was also identified, which may indicate the absence of activation of adhesion molecules at the initial stage of aortic valve calcification. Further study of the dynamics of sE - and sP -selectins content in the process of development of acceleration of blood flow in the aortic valve and the formation of stenosis is needed.

scholarly journals Properties and functions of TP/PD-ECGF — enzyme and angiogenic factor in norm and in neoplastic pathology

2021 ◽  
Vol 67 (6) ◽  
pp. 746-754
Author(s):  
Berta Borzenko ◽  
Anna Fedorova ◽  
Elena Bakurova ◽  
Elena Bogatyreva
Keyword(s):  
Inflammatory Diseases ◽  
Angiogenic Factor ◽  
Treatment Optimization ◽  
Prognostic Information ◽  
Apoptotic Pathway ◽  
Tumor Tissues ◽  
Dual Action ◽  
Appropriate Therapy ◽  
Rate Limiting

Thymidine phosphorylase is a protein which may has a dual action: it is a rate-limiting enzyme in thymidine metabolism and it is similar to the platelet – derived endothelial cell growth factor (PD/ECGF). The enzyme catalyzes the reversible reaction of phosphorolytic cleavage of thymidine to thymine and deoxyribose-1-phosphate. It has been found that TP has higher activity in tumor tissues. Also it is involved in a proliferative process in a wide variety of chronic inflammatory diseases. Increased expression of PD/ECGF in many tumors is associated with aggressive disease and/or poor prognosis. Its known that high TP activity is related to malignant angiogenesis and invasion. On the other hand, TP inhibits a hypoxia induced apoptotic pathway and enhances expression of various inflammatory cytokines and interferons. This apparent role of enzyme in tumor progression has prompted investigation a large number of TP inhibitors for applicability in chemotherapy backbone regimens. The enzymatic activity of PD/ECGF is being able to generate 5-fluorouracile from capecitabine and other precursors. Thus TP is identified as a prime target for developing novel anticancer therapies. The serum TP level in cancer patients provides useful prognostic information regarding both responses to chemotherapy and length of survival and should be used in planning appropriate therapy. TP could be suggested that control of individual enzyme activity in blood serum may be used as informative tool for monitoring of patients and treatment optimization.

The role of soluble intercellular adhesion molecules in neurodegenerative disorders

2005 ◽  
Vol 228 (2) ◽  
pp. 129-135 ◽  
Author(s):  
M. Rentzos ◽  
M. Michalopoulou ◽  
C. Nikolaou ◽  
C. Cambouri ◽  
A. Rombos ◽  
...  
Keyword(s):  
Adhesion Molecules ◽  
Neurodegenerative Disorders ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecules

ErbB4 acts as a suppressor in colitis and its associated carcinoma by negatively regulating cholesterol metabolism

2018 ◽  
Vol 40 (5) ◽  
pp. 680-686
Author(s):  
Hengli Ni ◽  
Lin Chen ◽  
Liming Song ◽  
Lina Sun ◽  
Hongxia Cui ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Significant Negative Correlation ◽  
Protective Role ◽  
The Cancer Genome Atlas ◽  
Clinical Samples ◽  
Cancer Genome Atlas ◽  
In Vitro Cell Lines ◽  
Rate Limiting

AbstractPreviously we reported that ErbB4 played a protective role in chronic liver injury and hepatocellular carcinoma. Herein, we examined the role of ErbB4 in the development of colitis-associated cancer (CAC) in ErbB4 knockout mice models, in vitro cell lines and clinical samples. We found that ErbB4 deficiency may lead to more severe inflammation, slower recovery and the development of CAC. Further, loss of ErbB4 could activate Kras by upregulating rate-limiting enzymes in cholesterol metabolism pathway through interacting with the transcription factor Srebf1. In clinic samples, ErbB4 is downregulated in colonic tissues from patients with Crohn’s disease. And data from The Cancer Genome Atlas also showed significant negative correlation between ErbB4 and several cholesterol metabolic enzymes. In summary, our study uncovers ErbB4 as a protector in the development of CAC, for its loss could activate Kras by upregulating cholesterol metabolism.

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