Electric vehicles have become critical mediators of intercellular communication in cancer. Tumor electric vehicles that circulate in body fluids, such as blood, contain the malignant features of their cells of origin, making them ideal biomarkers for detecting, evaluating and monitoring tumor growth in liquid biopsies. Extracellular vesicles (EVs) are small structures enclosed in lipid bilayers released by several cell types that play a critical role in intercellular communication. In atherosclerosis, electric vehicles have been involved in multiple pathophysiological processes, such as endothelial dysfunction, inflammation and thrombosis.
This review provides an updated overview of our current understanding of the roles of electric vehicles in atherosclerosis, stressing their potential as diagnostic biomarkers and their role in the pathogenesis of the disease. We analyze the different types of electric vehicles involved in atherosclerosis, the various charges they carry, their mechanisms of action and the various methods used to isolate and analyze them. In addition, we stress the importance of using animal models and relevant human samples to elucidate the role of electric vehicles in the pathogenesis of the disease. Overall, this review consolidates our current knowledge about electric vehicles in atherosclerosis and highlights their potential as promising targets for diagnosis and the treatment of diseases.
Atherosclerosis is a major cause of cardiovascular disease (CVD) that can lead to heart attacks, strokes, kidney failure and serious amputations (1—. Approximately 17.9 million people die annually from cardiovascular diseases (. Atherosclerosis is a chronic inflammatory process characterized by endothelial activation, the accumulation of lipoproteins and the recruitment of inflammatory cells, which produces plaques that gradually enlarge and restrict blood flow or are embolized, damaging the heart or peripheral tissues (. Current methods of diagnosing atherosclerosis are associated with rare but significant consequences related to the procedure and at a considerable cost.
(7,. Classic biomarkers, such as total cholesterol, low density lipoproteins (LDL) or serum triglyceride levels, are the reference diagnostic tests for atherosclerosis (. C-reactive protein, a nonspecific inflammatory marker, has become a clinical marker of residual risk in patients with atherosclerosis who have good cholesterol control (10, 1). Many of these biomarkers can diagnose CVD, but they cannot definitively predict the risk of stroke or myocardial infarction (MI).
New CVD biomarkers are needed that are cost-effective, improve detection and identify new treatment targets. As we enter the era of precision medicine, we need a more detailed understanding of biomarkers that can be used as reliable detection tools with metrics that serve as a guide for personalized intervention in order to to prevent devastating clinical events. In cancer, electric vehicle charging can promote neoplastic transformation and cell proliferation, contributing to the onset and progression of cancer (35 to 3). During atherogenesis, electric vehicles released by endothelial (EC) cells and immune cells promote leukocyte infiltration and plaque maturation (39-4).
This suggests that electric vehicles that circulate in plasma could serve as biomarkers for non-invasive diseases. In vitro and in vivo studies have demonstrated that circulating electric vehicles contain microRNAs, which can be biomarkers of neurodegenerative diseases (42-4) and CVDs (4) have several unique advantages compared to traditional biomarkers (4) electric vehicles circulate stably in almost all body fluids, can represent the current state of the disease by carrying a specific load of parental cells and can be collected sequentially. As a result, electric vehicles have significant potential as clinically valuable biomarkers capable of providing multiple, minimally intrusive assessments of disease status. Electric vehicles can also be used as a stable drug delivery system that protects the load from degradation (48 to 5).
Electric vehicles have numerous advantages over cell-based therapies in regenerative medicine, such as a long lifespan, ease of transportation, long-term storage, and lack of replication (55 to 5). As drug delivery vehicles, they overcome synthetic drug carriers by crossing tissue and cellular barriers (4). In preclinical studies, electric vehicles have been used as a drug delivery system. For example, exosome-mediated administration of siRNA has been used in Alzheimer's disease (4), while exosomes derived from mesenchymal stem cells have been used to treat ischemic lung injury (5) and eye disorders (5). However, there is a need to better understand the dynamics of electric vehicle circulation, targeting, internalization and intracellular traffic routes to take full advantage of the therapeutic potential.
Despite significant advances in technology for the insulation and characterization of electric vehicles, limitations and challenges persist. However, as developing technology continues to refine research on electric vehicles, it is increasingly evident that electric vehicles play a crucial role in biological processes, control diseases and have become a new avenue in atherosclerosis research. Electric vehicles can serve as diagnostic and therapeutic tools for many cardiovascular diseases. Levels of EV in blood, urine, and saliva have been linked to clinical risk in patients with stable CVD (70) (Table.
Elevated electric vehicles are associated with risk factors such as smoking, diabetes and hypercholesteremia (8). The abundance of electric vehicles carried in plasma reflects the possibility of using these electric vehicles as biomarkers of CVD and, in particular, that electric vehicles derived from specific cell types, such as EC, leukocytes and platelets, are correlated with CVD (8). A previous study used surface markers expressed on electric vehicles to purify and isolate cell-specific electric vehicles, followed by enrichment and analysis of the electric vehicle charge. In electric vehicles isolated from plasma, upregulation of CD14 was associated with a higher risk of onset of an ischemic stroke (80), while increased cystatin C and polygenic immunoglobulin receptors were associated with acute coronary syndrome (7).
Circulating electric vehicles of different cellular origins and their different charge (e.g., this suggests that electric vehicles play a role in immune response, vascular remodeling, endothelial dysfunction and apoptosis, all of which underlie atherosclerosis (92, 9). Studies have shown that electric vehicles derived from leukocytes, neutrophils and activated platelets were significantly higher in patients with atherosclerosis (94, 9.9). Electric vehicles carried in plasma may be useful as biomarkers of atherosclerosis, but accuracy must be improved to detect changes in electric vehicle counts in specific cell types. As electric vehicles are heterogeneous in size, composition and cellular origin, this makes it difficult to identify specific populations and their correlation with disease (4). In addition to the heterogeneity of electric vehicles, clinical variables (e.g., most of our current understanding of the role of electric vehicles in atherosclerosis) have been obtained from studies using electric vehicles derived from cell cultures, which may not accurately represent electric vehicles found in vivo.
However, electric vehicles have been found to exert a significant influence on a variety of proatherogenic processes, such as inflammation, thrombosis and angiogenesis (8). In particular, EC-derived electric vehicles have been implicated in endothelial dysfunction (106, 10) and vascular inflammation (10), which may contribute to the development of early atherosclerotic plaques. In addition, EC-derived electric vehicles can communicate with macrophages (109, 1) and SMC (111—11) to regulate vascular disease, while electric vehicles derived from monocytes have been found to modulate vascular inflammation and cell death (114-11). In addition, electric vehicles derived from foam cells have been shown to regulate SMC migration, which could accelerate the progression of atherosclerotic lesions (11).
Platelets, dendritic cells and monocytic cells have also been shown to cause macrophage apoptosis (118-12), which may contribute to the development and progression of atherosclerosis. In addition, electric vehicles have been found to play several multifaceted and environmentally dependent roles in other cellular processes, such as endothelial permeability (12), pro-inflammatory and anti-inflammatory signaling (124 to 12), leukocyte transmigration and lipid accumulation (127 to 12), SMC proliferation (130), intravascular calcification (13), extracellular matrix remodeling (13) and plaque rupture. Taken together, the evidence suggests a substantial role of electric vehicles in the pathogenesis of atherosclerosis, which emphasizes the need for more research on the mechanisms underlying electric vehicle-mediated intercellular communication in this disease. New technologies, such as flow cytometry and the analysis of individual electric vehicles, will increase the accuracy of detection and provide more details about the phenotypes of electric vehicles specific to each cell, their charge and their role in regulating the disease. Until then, an emerging resource for electric vehicle studies is the development of multicellular models for your follow-up.
Despite recent discoveries, understanding the space-time distribution and physiological activities of electric vehicles in vivo remains a challenge. Little is known about the biological activities of electric vehicles in vivo, including tissue distribution, blood levels, and elimination dynamics. Electric vehicles have been investigated in several animal models that simulate diseases, including mice, rats and zebrafish. Electric vehicles have also been studied using more advanced organisms for models of diseases such as cancer (137, 13) and neurological disorders (139-14).
For example, a murine model was used to determine the therapeutic effects of immunity and electric vehicles derived from matrix regulatory cells on idiopathic pulmonary fibrosis (14). Several studies have used the rat model to study the role of electric vehicles in spinal cord injuries (143, 14) and repetitive stress (14). Rat models have also been used to investigate the role of electric vehicles in spinal cord injuries (143, 14). The therapeutic potential of electric vehicles to treat diseases such as small cerebral vessel disease (14, color) -post-surgical skin fistula (14) and congenital diaphragmatic hernia (14. EV), known to carry biologically active charges, seem to play an important role in the pathogenesis of atherosclerosis. However, studying electric vehicles derived from the plate is a challenge due to the limited accessibility and the complex composition of the plates.
Therefore, researchers have focused on studying electric vehicles in circulation, in particular those found in plasma, to obtain information on the biology of atherosclerosis. Although plasma can be easily accessed, identifying reliable biomarkers is a challenge, and combining biomarkers with clinical events may not fully reflect the state of the disease. Therefore, it is necessary to determine if the affected regions release electric vehicles to circulation, which could serve as a possible biomarker. The combined evaluation of electric vehicles based on the circulation and plates of the same patient is a possible approach, which represents a promising and significant strategy for a study of atherosclerosis.
Electric vehicles have been recognized as important components in the pathogenesis of atherosclerosis. Immune-derived electric vehicles and electronic devices are involved in the development and destabilization of atherosclerotic plaques. Plasma electric vehicles can transmit information related to the vulnerability of atherosclerotic plaques and can serve as potential biomarkers of atherosclerosis and its associated complications, such as myocardial infarction and strokes. In addition, the prospect of using electric vehicles as therapeutic targets for atherosclerosis has recently gained substantial interest.
While much remains to be done to improve tools and the standardization of research on electric vehicles, electric vehicles represent an encouraging area for future research in the field of atherosclerosis and have the potential to provide new knowledge about the diagnosis, treatment and prevention of this chronic inflammatory disease. SP is supported by the Postdoctoral Fellowship Award from the Toronto General Hospital Research Institute. KH is supported by the PJT178006 grant from the Canadian Institute for Health Research (CIHR), the Canadian Heart and Stroke Foundation (award for a new researcher), Vascular Cures (Wylie grant), the Blair chair in vascular surgery at the beginning of his career, the Peter Munk Heart Center and the Network of University Health. The authors declare that the research was carried out in the absence of any commercial or financial relationship that could be interpreted as a possible conflict of interest.
Walt's laboratory has developed an assay and a platform to collect new biomarkers in the form of extracellular vesicles (EVs) released by cells. As a result, a wider variety of electric vehicles with unmatched quality, quantity and purity can be obtained. Electric vehicles are of incredible value to the scientific and medical communities, as they can provide a better understanding of how diseases originate in organs and tissues that are generally inaccessible for diagnosis, such as the brain. This platform can also enable better and earlier diagnosis of deadly diseases such as ovarian cancer, and can discover new disease targets to accelerate drug discovery.
Current clinical tools for the diagnosis of breast cancer (BC) are insufficient, but liquid biopsy of different body fluids has recently emerged as a minimally invasive strategy that provides a real-time snapshot of tumor biomarkers for early diagnosis, active monitoring of progression and recurrence after treatment. Extracellular vesicles (EVs) are nanometric membranous structures 50 to 1000 nm in diameter that cells release into biological fluids. Electric vehicles contain proteins, nucleic acids and lipids that play a fundamental role in tumorigenesis and metastasis through communication between cells. Small electric vehicle (sEVs) proteins and miRNAs, which range in size between 50 and 150 nm, are being investigated as a potential source of new BC biomarkers using proteomics based on mass spectrometry and next-generation sequencing.
This review covers recent advances in sEV isolation and single sEV analysis technologies, and summarizes the identified sEV protein and miRNA biomarkers for the diagnosis, prognosis and chemoresistance of BC. The limitations of current research on sEV biomarkers are analyzed, as well as possible future applications. Proteomic analysis of circulating extracellular vesicles identifies potential markers of breast cancer progression, recurrence and response. Since the method is image-based, it allows for concomitant size analyses and the expression of molecular biomarkers in individual vesicles.
Possible roles of extracellular vesicles in the pathophysiology, diagnosis and treatment of autoimmune diseases. The exhaustive characterization of hepatocyte-derived extracellular vesicles identifies the miRNA-based direct regulation of hepatic stellate cells and the upregulation of IL-1beta and IL-17 of DAMP-based hepatic macrophages in mice with alcoholic hepatitis. Therapeutic potential of extracellular vesicles for treatment of diabetes and diabetic complications. Isolation of small extracellular vesicles from human serum by a combination of ultracentrifugation with polymer-based precipitation.
In particular, circulating tumor-derived extracellular vesicles (EVs) represent a promising environment because the detached vesicles are stable, contain substances derived from parental cells2,3 and are abundant in the more advanced stages of the disease. Identification of different nanoparticles and subsets of extracellular vesicles using asymmetric field-flow fractionation. The University Medical Center of Ljubljana completed a clinical trial using autologous plasma rich in platelets and extracellular vesicles (PVRP) to treat chronic inflammation of the temporary bone cavities that occurs after the removal of the posterior wall of the external auditory canal through cholesteatoma surgery open technique. Self-assembly of nanoparticles with a metal-organic structure similar to extracellular vesicles for the protection and intracellular delivery of biofunctional proteins.
The review summarizes the main preclinical and clinical applications of extracellular vesicles and exosomes as biomarkers and therapeutic tools. On the contrary, MASEV is fast and inexpensive, is designed for the analysis of cancer biomarkers and can be extended to other types of vesicles (e.g., lipidomic analysis of extracellular vesicles of adipose origin reveals a specific classification of EV lipids) that is indicative of the metabolic status of obesity. Local administration of stem cell-derived extracellular vesicles in a thermosensitive hydrogel promotes a prohealing effect in a model of post-surgical colocutaneous fistula in rats. Improving functional recovery through intralesional application of extracellular vesicles in a model of traumatic spinal cord injury in rats.
