Introduction
Microvesicles are called ectosomes or microparticles. These are extracellular vesicles (EVs) and are secreted from cell membranes. Previously, these were considered mere cell waste but have regained their importance through continued research. They are found to be important in intercellular communication. EVs are used broadly by prokaryotic and eukaryotic cells of plants, bacteria, and humans.
What Is a Microvesicle?
Microvesicles are released from cell membranes. These are types of EVs. Microvesicles and EVs are found in multicellular organisms' tissues and many body fluids. These may be situated in between the cells. Microvesicles separated by phospholipids bilayer are either small in size of 30 nm (nanometer) or large in size of 1000 nm in diameter. These are larger than the exosomes present in the cells.
Microvesicles play an important role in intercellular communication. These help in transporting mRNA (messenger ribonucleic acid), miRNA, and proteins in between cells. They reflect antigenic content and help in cell signaling. They participate in many physiological processes like antitumor effects, tumor immunosuppression, metastasis, tumor-stromal interactions, angiogenesis, and tissue regeneration. These remove misfolded proteins, cytotoxic substances, and metabolic wastes from cells. Their changes show diseases like cancer.
Different types of cells are responsible for the release of microvesicles. They are released from megakaryocytes, monocytes, platelets, neutrophils, tumor cells, and the placenta. Microvesicles released from the activation of platelets contain CD154 and help increase immune response.
Endothelial microparticles are small vesicles secreted from endothelial cells and found in the blood. Their presence in the circulating blood is considered normal, but increased endothelial microparticles may indicate certain diseases like hypertension and cardiovascular diseases. These can prevent apoptosis in recipient cells.
How Microvesicles Are Formed?
Microvesicles are formed from plasma membranes as particles into extracellular space by budding outwardly. The budding process includes multiple signaling pathways, increased intracellular calcium, and reorganization in the structure of the cell. The formation and release of the vesicle involve contractile mechanisms. This helps in pulling the opposite membranes together before pinching membrane connections. After this, an ejection of vesicles into the extracellular space occurs.
The budding occurs at a particular location of the cell membrane. These locations should contain lipids and proteins that show the properties of microvesicles. After forming, these are seen in extracellular space; some may travel and be seen in body fluids.
What Is the Mechanism of the Shedding of Microvesicles?
After the formation of microvesicles, at last, one can observe cell death. This causes apoptotic blebbing. Formation and cell death both need energy. The plasma membrane of the cell contains phospholipids that are distributed asymmetrically. When there is cellular stimulation and apoptosis, there is an increase in cytosolic calcium, leading to a disrupted plasma membrane phospholipid asymmetry. Lipid imbalance is initiated and causes plasma budding. Then, there is a release of microvesicles.
What Are the Molecular Contents of Microvesicles?
Microvesicles contain many molecules in it. The content inside it depends on the origin of the cell and the molecular processes responsible for its formation. Microvesicles do not contain mitochondria, Golgi, endoplasmic reticulum, or an associated DNA-containing (deoxyribonucleic acid) nucleus. They contain membrane lipids and membrane proteins. A phospholipid bilayer surrounds proteins.
What Is the Role of Microvesicles on the Target Cells?
Microvesicles interact with other cells and bind to them through receptors present on the membrane. Molecules on the surface of microvesicles allow it to bind with receptors. After binding with other cells, they exchange substances with each other. Because of this interaction, there is a fusion between the target cell and microvesicles. There is a transportation of components like bioactive molecules, lipids, genetic material, and proteins. There can be transport of mRNA and proteins that contribute to proteomic properties of target cells and transfer of miRNA that regulate gene expression by altering mRNA turnover.
Degradation: Microvesicle disassembly is responsible for releasing signaling components or molecules. Microvesicles that are derived from dendritic cells, macrophages, and microglia can use this mechanism to release growth factors.
Fusion: Proteins on the microvesicle combine with specific molecules present on the surface of the target cells. The microvesicle gets bound to the target cell and fuses with the cell membrane. After fusing, it releases nucleotides and soluble proteins into the cytosol of target cells. Apart from this, it incorporates lipids and proteins into the cell membrane.
Internalization: When microvesicles are bound and fused with target cells, proteins, and lipids get into endosomes. These endosomes mature into lysosomes. This, in turn, caused the disassembly of microvesicles and their contents. In such cases, the signal gets ignored.
Transcytosis: Endosomes move inside the cell and fuse with the cell membrane after internalization. This is called transcytosis. This may result in the release of microvesicles into extracellular space or adjacent cells. Hence, it was known that microvesicles can cross biological barriers.
Contact-Dependent Signaling: In such cases, microvesicles do not get fused with the cell membrane; instead, molecules present on the surface of the microvesicle interact with specific receptor molecules responsible for various signaling pathways.
Promoting Aggressive Tumor Phenotypes: The oncogenic receptor present in certain aggressive tumors may metastasize to non-grade tumor cells through microvesicles.
Promoting Angiogenesis: Angiogenesis usually occurs when endothelial cells proliferate to form a vascular matrix. Many studies have shown that tumor-associated microvesicles release proangiogenic factors that help in the proliferation of endothelial cells, angiogenesis, and tumor growth. Microvesicles released by tumor cells, when taken up by endothelial cells, tend to cause angiogenesis.
Involvement in Multidrug Resistance:
Drugs like Doxorubicin used to treat cancer may accumulate in microvesicles. This causes a decrease in cellular levels of the drug, leading to drug resistance.
Interference With Antitumor Immunity:
Microvesicles of certain tumor cells exhibit molecules that may induce apoptosis in T cells, reducing their effectiveness of immunity.
Impact on Tumor Metastasis:
Extracellular matrix degradation is responsible for tumor growth and metastasis. Tumor-derived microvesicles contain certain proteolytic enzymes. When these proteases are released, they can degrade the extracellular matrix and invade surrounding tissues.
Cellular Origin of Microvesicles:
Many cells release microvesicles. Though it is present in normal individuals, its number variation, cellular origin, and composition may indicate disease states.
Cardiovascular Disease:
Microvesicles play a role in the development of cardiovascular diseases. Monocyte-derived microparticles are responsible for the exacerbation of atherosclerosis. Microvesicles also play a role in inducing the coagulation process.
Inflammation:
Microvesicles contain cytokines. These cytokines are responsible for inducing inflammation through various pathways. These cells further cause the release of more microvesicles that cause additive effects.
Neurological Disorders:
Microvesicles are a part of many vascular diseases, inflammations, strokes, and multiple sclerosis.
Detection of Cancer:
Tumor-related microvesicles are seen in a cancer patient's blood, urine, and other body fluids. The composition of microvesicles of tumor cells differs from that of microvesicles of normal cells. Hence, the plasma microvesicle concentration that contains molecular marks can help indicate disease status. This can be used to detect cancer.
Microvesicles in Rheumatoid Arthritis:
Rheumatoid arthritis is an autoimmune disorder that affects the joints of the body. Activated platelets secrete microvesicles from the plasma membrane of platelets. These microvesicles are seen in synovial fluid in the joints and increase inflammation.
Biological Markers for Disease:
Apart from detecting cancer, microvesicles can be used to know the prognosis of different diseases. Many neurological diseases show increased specific microvesicles.
Mechanism for Drug Delivery:
Microvesicles circulating in the blood can help in drug delivery to specific sites. This property helps in reducing the dose of a drug as well as targeting the side effects of the drug.
Conclusion
Microvesicles are extracellular vesicles that are present in the cells and body fluids. They have a role in normal and diseased status as well. Hence, it is important to know about microvesicles and their role in the human body.
