Current Knowledge on the Role of Monocytes and Macrophages in the Pathogenesis of Non-AIDS Defining Events: Mechanisms, Host Factors, and Therapeutic Implications | Chapter 10 | Medical Science: Updates and Prospects Vol. 4

 

Monocytes and macrophages play a crucial role in the development of HIV infection, contributing not only to viral persistence but also to the development of non-AIDS-defining events (nADEs) in People Living with HIV (PLWH). These innate immune cells serve as long-lived viral reservoirs, driving chronic inflammation through persistent immune activation, oxidative stress, and tissue-specific damage. HIV-infected monocytes infiltrate tissues such as the cardiovascular system, liver, kidneys, and central nervous system, where they differentiate into macrophages and release pro-inflammatory cytokines (e.g., TNF-α, IL-6), reactive oxygen species (ROS), and matrix metalloproteinases (MMPs). These mediators promote endothelial dysfunction, fibrosis, and organ damage, underpinning conditions like atherosclerosis, neurocognitive disorders, and hepatorenal disease. Emerging evidence highlights the importance of macrophage polarisation (M1/M2 imbalance) and epigenetic modifications in sustaining inflammation, even during antiretroviral therapy (ART). Besides persistent immune activation, the ability of these cells to cause tissue-specific damage is significantly influenced by host genetic factors, such as polymorphisms in the APOL1 and CCL2 genes, which can determine the severity of end-organ diseases like HIV-associated nephropathy. Additionally, epigenetic reprogramming of monocytes and macrophages—triggered by HIV proteins and the inflammatory environment—establishes a lasting pro-inflammatory state that remains despite ART. This reprogramming, marked by changes in histone modifications and DNA methylation, sustains mechanisms of tissue damage. Understanding these processes and their interaction with host factors provides critical insights for developing targeted treatments, including immunomodulators, antioxidants, and strategies for reservoir elimination. This review summarises current knowledge on how monocytes and macrophages contribute to the pathogenesis of nADEs. It explores potential new therapeutic approaches to reduce chronic inflammation and enhance clinical outcomes in PLWH.

 

 

Author(s) Details

Samuel Adinoyi Adavba
Kaduna State University, Kaduna, Nigeria.

 

Please see the book here :- https://doi.org/10.9734/bpi/msup/v4/6480

 

Increased Uptake of Oxidized LDL by Macrophages from Type 2 Diabetics is Inhibited by Polyamines: An Advanced Study | Chapter 10 | Advanced Concepts in Pharmaceutical Research Vol. 5

Patients with diabetes mellitus have an increased incidence of atherosclerotic cardiovascular disease. To date, considerable evidence supports a role for oxidative modified low density lipoprotein (LDL) in the pathogenesis of atherosclerosis. The aim of this study was to evaluate the effect of polyamines putrescine, spermidine and spermine on human LDL oxidation and to assess the ability of macrophages derived from type 2 diabetic patients to uptake oxLDL. Polyamine effect was compared with α-tocopherol. Four healthy subjects and eight type 2 diabetic patients were included in this study. Data were expressed as the mean S.D. Significance among experimental groups was calculated by one-way ANOVA test and Tukey HSD test for multiple comparisons, using the SPSS Program. To characterize type 2 diabetic patients and non-diabetic subjects, laboratory tests were carried out. Glucose, glycated haemoglobin (HbA1C), triglycerides, low (LDL) and high-density lipoproteins (HDL) and serum lipid peroxidation were measured in blood. The study was performed in three stages. For each stage, ten experimental conditions comparing the effect of polyamines with α-tocopherol (10 μM solutions) on LDL oxidation and the uptake of oxLDL by macrophages were analyzed. MDA concentration was found to be significantly higher in type 2 diabetic patients compared to healthy subjects (5.6 ± 0.58 vs. 2.66 ± 0.31 μM MDA, respectively, (P < 0.05)). Percent of macrophages containing oxLDL was determined by means of red oil staining. The uptake of oxLDL by macrophages derived from diabetic patients was clear. The uptake of oxLDL was inhibited when the oxidation was prevented by polyamines or a-tocopherol. Spermine showed high antioxidant capacity (96.67 ± 1.53% vs. 25.67 ± 2.30%) compared to a-tocopherol (96.67 ± 1.53% vs. 47.00 ± 7.20%) at the concentration tested.

In conclusion, polyamines especially spermine, has a potent antioxidant effect compared to a-tocopherol on human LDL oxidation, followed by spermidine and putrescine. The results have clinical relevance in the diabetic complications and add knowledge on the role of polyamines as natural antioxidants. This research is not a clinical evaluation rather a functional analysis utilizing clinical samples.

Author(s) Details:

Francisco L. Balderas,
Medical Research Unit in Metabolic Diseases, Specialities Hospital, National Medical Center, Mexican Institute of Social Security, P.O. Box A-047, Mexico City, 06703 D.F., Mexico and School of Medicine, Benemerita Universidad Autonoma de Puebla, Campus Tehuacan, Puebla, Mexico.

Marina Quezada-Larios,
Angiology Department, Specialities Hospital, National Medical Center, Mexican Institute of Social Security, Mexico City, Mexico.

Ethel Awilda García Latorre,
Immunology Department, National School of Biological Sciences, I.P.N., Mexico City, Mexico.

José D. Méndez,
Medical Research Unit in Metabolic Diseases, Specialities Hospital, National Medical Center, Mexican Institute of Social Security, P.O. Box A-047, Mexico City, 06703 D.F., Mexico and School of Odontology, National Autonomous University of Mexico, Mexico City, 04510 D.F., Mexico.

Please see the link here: https://stm.bookpi.org/ACPR-V5/article/view/13287

Atherogenic Role of LDL(-) on Macrophages | Chapter 10 | Advanced Research in Biological Science Vol. 6

This unit assesses the inference of an inflammatory profile and the build-up of intracellular lipids in macrophages by electronegative LDL (LDL(-)). LDL(-), a modified LDL that is to say present in blood, exerts atherogenic belongings on endothelial cells and monocytes. Abundant studies focusing on LDL(-) have since existed performed, and ultimate widely accepted idea is that LDL(-) is a pool of LDL pieces modified by various mechanisms. In the study shown in this place chapter, LDL(-) and artificial-modified LDLs (oxidized, aggregated, acetylated) were increased macrophages derived from THP1 monocytes over-meaning CD14 (THP1-CD14). Then, cytokine release, cell distinction, lipid accumulation, and deoxyribonucleic acid expression were measured by ELISA, flow cytometry, thin-coating chromatography, and real-period PCR, respectively. Compared to added modified LDLs, LDL(-) induced THP1-CD14 macrophages to produce more cytokines. Additionally, LDL(-) stimulated semantic alterations linked to mature macrophages. HDL and antagonistic-TLR4 were added to compensate these effects. Macrophages ingested abundant amounts of LDL(-), which was the main inventor of intracellular lipid buildup in lipid droplets improved in triglycerides. In contrast to redness, the addition of anti-TLR4 had no effect on lipid aggregation, thus suggesting an rude answer pathway alternative to TLR4. In our study, compared to additional in vitro-reduced LDLs, LDL(-) was the main inductor of GM-CSF, IL6, and IL10 release, and it had a similar effect on IL1 β than oxLDL. This occurred in the deficiency of changes in cell increase or mortality. In this regard, LDL(-) upregulated the verbalization of the scavenger receptors CD36 and LOX-1, in addition to several genes involved in TG build-up. In summary, LDL(-) promoted macrophage distinction, inflammation, and triglyceride-enriched lipid beads formation in THP1-CD14 macrophages, presumably through different receptors. The complex interaction 'tween these pathways should be tried in future studies. Taken together, our judgments highlight new meaningful actions of LDL(-) on macrophage activation in the framework of the development of atherosclerosis.

Author(s) Details:

Núria Puig,
Cardiovascular Biochemistry, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain and Department of Biochemistry and Molecular Biology, Faculty of Medicine, Building M, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès, Barcelona, Spain.

Berta Casaldàliga,
Cardiovascular Biochemistry, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain and Department of Biochemistry and Molecular Biology, Faculty of Medicine, Building M, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès, Barcelona, Spain.

Pol Camps-Renom,
Department of Neurology, Stroke Unit, Hospital de la Santa Creu i Sant Pau and IIB-Sant Pau, Barcelona, Spain.

Francesc Jiménez-Altayó,
Department of Pharmacology, Neuroscience Institute, Faculty of Medicine, UAB, Cerdanyola del Vallès, Barcelona, Spain.

Elena Jiménez-Xarrié,
Department of Neurology, Stroke Unit, Hospital de la Santa Creu i Sant Pau and IIB-Sant Pau, Barcelona, Spain.

Jose Luis Sánchez-Quesada,
Cardiovascular Biochemistry, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain and CIBER of Diabetes and Metabolic Diseases (CIBERDEM), Madrid, Spain.

Sonia Benitez,
Cardiovascular Biochemistry, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain and CIBER of Diabetes and Metabolic Diseases (CIBERDEM), Madrid, Spain.

Please see the link here: https://stm.bookpi.org/ARBS-V6/article/view/12843

Inspiration from New Discoveries in Vascular Endothelial Cell Growth: A Bold Conjecture about Mature Cell Growth | Chapter 4 | Current Approaches in Science and Technology Research Vol. 4

 Scientists have been trying to figure out how to speed up the proliferation of endothelial cells (EC) in vascular biomaterials and devices so that they can repair, regenerate, or build an endothelial monolayer as quickly as feasible. By directly encouraging EC growth on the surface while suppressing smooth muscle cells (SMC) and macrophages, a variety of approaches have been devised to achieve this goal. However, a 2017 discovery that the endothelium monolayer in regenerated tissues does not come into touch with implanted biomaterials provided us with new inspiration, and offered the idea of "spatiotemporal orderliness of function" to describe macrophage actions. This objective phenomena and law should be followed by SMC and EC on implanted biomaterials in time and space, as well as the functionalities endowed for the implants' surfaces. In the following research, we discovered a series of new mysteries of EC growth, much to our amazement. These minor subtleties, which are often overlooked in scientific research, have the potential to provide new guidelines for universal mature cell proliferation, in addition to explaining the causes for varied blood implantation failures.

Author(s) Details

Jingan Li
School of Materials Science and Engineering & Henan Key Laboratory of Advanced Magnesium Alloy, Zhengzhou University, 100 Science Road, Zhengzhou 450001, PR China.

Yachen Hou
School of Materials Science and Engineering & Henan Key Laboratory of Advanced Magnesium Alloy, Zhengzhou University, 100 Science Road, Zhengzhou 450001, PR China.

Kun Zhang
School of Life Science, Zhengzhou University, 100 Science Road, Zhengzhou 450001, PR China.

View Book :- https://stm.bookpi.org/CASTR-V4/article/view/1038