-
Current Atherosclerosis Reports Nov 2017The cell surface-attached extracellular glycocalyx (GCX) layer is a major contributor to endothelial cell (EC) function and EC-dependent vascular health and is a first... (Review)
Review
PURPOSE OF REVIEW
The cell surface-attached extracellular glycocalyx (GCX) layer is a major contributor to endothelial cell (EC) function and EC-dependent vascular health and is a first line of defense against vascular diseases including atherosclerosis. Here, we highlight our findings regarding three GCX-dependent EC functions, which are altered when GCX is shed and in atherosclerosis. We discuss why the GCX is a viable option for the prevention and treatment of atherosclerosis.
RECENT FINDINGS
GCX regulated EC activities such as barrier and filtration function, active cell-to-cell communication, and vascular tone mediation contribute to function of the entire vascular wall. Atheroprone vessel regions, including bifurcation sites, exhibit breakdown in GCX. This GCX degradation allows increased lipid flux and thereby promotes lipid deposition in the vessel walls, a hallmark of atherosclerosis. GCX degradation also alters EC-to-EC communication while increasing EC-to-inflammatory cell interactions that enable inflammatory cells to migrate into the vessel wall. Inflammatory macrophages and foam cells, to be specific, appear in early stages of atherosclerosis. Furthermore, GCX degradation deregulates vascular tone, by causing ECs to reduce their expression of endothelial nitric oxide synthase (eNOS) which produces the vasodilator, nitric oxide. Loss of vasodilation supports vasoconstriction, which promotes the progression of atherosclerosis. Common medicinal atherosclerosis therapies include lipid lowering and anti-platelet therapies. None of these treatments specifically target the endothelial GCX, although the GCX is at the front-line in atherosclerosis combat. This review demonstrates the viability of targeting the GCX therapeutically, to support proper EC functionality and prevent and/or treat atherosclerosis.
Topics: Animals; Atherosclerosis; Endothelial Cells; Endothelium, Vascular; Glycocalyx; Humans; Models, Animal; Molecular Targeted Therapy
PubMed: 29127504
DOI: 10.1007/s11883-017-0691-9 -
Current Cardiology Reviews 2020The article provides an overview of current views on the role of biomechanical forces in the pathogenesis of atherosclerosis. The importance of biomechanical forces in... (Review)
Review
The article provides an overview of current views on the role of biomechanical forces in the pathogenesis of atherosclerosis. The importance of biomechanical forces in maintaining vascular homeostasis is considered. We provide descriptions of mechanosensing and mechanotransduction. The roles of wall shear stress and circumferential wall stress in the initiation, progression and destabilization of atherosclerotic plaque are described. The data on the possibilities of assessing biomechanical factors in clinical practice and the clinical significance of this approach are presented. The article concludes with a discussion on current therapeutic approaches based on the modulation of biomechanical forces.
Topics: Atherosclerosis; Biomechanical Phenomena; Disease Progression; Humans; Mechanotransduction, Cellular; Stress, Mechanical
PubMed: 31362692
DOI: 10.2174/1573403X15666190730095153 -
Nature Reviews. Cardiology Dec 2017The gut microbiota has been associated with many different disorders, including cardiovascular diseases. A new study by Jie and colleagues is the first large... (Review)
Review
The gut microbiota has been associated with many different disorders, including cardiovascular diseases. A new study by Jie and colleagues is the first large case–control study to examine directly the enrichment of certain communities of gut bacteria in patients with atherosclerotic cardiovascular disease compared with control individuals.
Topics: Atherosclerosis; Gastrointestinal Microbiome; Humans; Metagenomics
PubMed: 29099096
DOI: 10.1038/nrcardio.2017.169 -
Journal of the American College of... Feb 2021
Topics: Atherosclerosis; Cardiovascular Diseases; Fluorodeoxyglucose F18; Heart Disease Risk Factors; Humans; Positron-Emission Tomography; Risk Factors
PubMed: 33602473
DOI: 10.1016/j.jacc.2020.12.046 -
Circulation Research Jun 2016Many aspects of human health and disease display daily rhythmicity. The brain's suprachiasmic nucleus, which interprets recurring external stimuli, and autonomous... (Review)
Review
Many aspects of human health and disease display daily rhythmicity. The brain's suprachiasmic nucleus, which interprets recurring external stimuli, and autonomous molecular networks in peripheral cells together, set our biological circadian clock. Disrupted or misaligned circadian rhythms promote multiple pathologies including chronic inflammatory and metabolic diseases such as atherosclerosis. Here, we discuss studies suggesting that circadian fluctuations in the vessel wall and in the circulation contribute to atherogenesis. Data from humans and mice indicate that an impaired molecular clock, disturbed sleep, and shifting light-dark patterns influence leukocyte and lipid supply in the circulation and alter cellular behavior in atherosclerotic lesions. We propose that a better understanding of both local and systemic circadian rhythms in atherosclerosis will enhance clinical management, treatment, and public health policy.
Topics: Animals; Atherosclerosis; Circadian Rhythm; Healthy Lifestyle; Humans; Lipid Metabolism; Sleep
PubMed: 27340272
DOI: 10.1161/CIRCRESAHA.116.308034 -
BMC Public Health Apr 2016Epidemiological and experimental studies have suggested that exposure to particulate air pollution may promote progression of atherosclerosis. (Review)
Review
BACKGROUND
Epidemiological and experimental studies have suggested that exposure to particulate air pollution may promote progression of atherosclerosis.
METHODS
In the present study, the characteristics and trends of the research field of particulate matter (PM) and atherosclerosis were analyzed using bibliometric indicators. Bibliometric analysis was based on original papers obtained from PubMed/MEDLINE search results (from 1973 to 2014) using Medical Subject Headings (MeSH) terms. A fully-detailed search strategy was employed, and articles were imported into the Thomson Data Analyzer (TDA) software.
RESULTS
The visualizing network of the collaborative researchers was analyzed by Ucinet 6 software. Main research topics and future focuses were explored by co-word and cluster analysis. The characteristics of these research articles were summarized. The number of published articles has increased from five for the period 1973-1978 to 89 for the period 2009-2014. Tobacco smoke pollution, smoke and air PM were the most studied targets in this research field. Coronary disease was the top health outcome posed by PM exposure. The aorta and endothelium vascular were the principal locations of atherosclerotic lesions, which were enhanced by PM exposure. Oxidative stress and inflammation were of special concern in the current mechanistic research system. The top high-frequency MeSH terms were clustered, and four popular topics were further presented.
CONCLUSION
Based on the quantitative analysis of bibliographic information and MeSH terms, we were able to define the study characteristics and popular topics in the field of PM and atherosclerosis. Our analysis would provide a comprehensive background reference for researchers in this field of study.
Topics: Atherosclerosis; Bibliometrics; Disease Progression; Environmental Exposure; Humans; Particulate Matter; Research
PubMed: 27093947
DOI: 10.1186/s12889-016-3015-z -
Archives of Medical Research Jan 2017Atherosclerosis and cancer are chronic diseases considered two of the main causes of death all over the world. Taking into account that both diseases are multifactorial,... (Review)
Review
Atherosclerosis and cancer are chronic diseases considered two of the main causes of death all over the world. Taking into account that both diseases are multifactorial, they share not only several important molecular pathways but also many ethiological and mechanistical processes from the very early stages of development up to the advanced forms in both pathologies. Factors involved in their progression comprise genetic alterations, inflammatory processes, uncontrolled cell proliferation and oxidative stress, as the most important ones. The fact that external effectors such as an infective process or a chemical insult have been proposed to initiate the transformation of cells in the artery wall and the process of atherogenesis, emphasizes many similarities with the progression of the neoplastic process in cancer. Deregulation of cell proliferation and therefore cell cycle progression, changes in the synthesis of important transcription factors as well as adhesion molecules, an alteration in the control of angiogenesis and the molecular similarities that follow chronic inflammation, are just a few of the processes that become part of the phenomena that closely correlates atherosclerosis and cancer. The aim of the present study is therefore, to provide new evidence as well as to discuss new approaches that might promote the identification of closer molecular ties between these two pathologies that would permit the recognition of atherosclerosis as a pathological process with a very close resemblance to the way a neoplastic process develops, that might eventually lead to novel ways of treatment.
Topics: Apoptosis; Atherosclerosis; Calcium; Cell Proliferation; Epigenesis, Genetic; Humans; Inflammation; MicroRNAs; Neoplasms; Neovascularization, Pathologic; Neovascularization, Physiologic; Oxidative Stress
PubMed: 28577865
DOI: 10.1016/j.arcmed.2017.03.005 -
Reumatologia Clinica 2018
Topics: Atherosclerosis; Humans; Osteoarthritis
PubMed: 30205874
DOI: 10.1016/j.reuma.2018.08.001 -
International Journal of Molecular... Jan 2023The gut microbiome plays a major role in human health, and gut microbial imbalance or dysbiosis is associated with disease development. Modulation in the gut microbiome... (Review)
Review
The gut microbiome plays a major role in human health, and gut microbial imbalance or dysbiosis is associated with disease development. Modulation in the gut microbiome can be used to treat or prevent different diseases. Gut dysbiosis increases with aging, and it has been associated with the impairment of gut barrier function leading to the leakage of harmful metabolites such as trimethylamine (TMA). TMA is a gut metabolite resulting from dietary amines that originate from animal-based foods. TMA enters the portal circulation and is oxidized by the hepatic enzyme into trimethylamine oxide (TMAO). Increased TMAO levels have been reported in elderly people. High TMAO levels are linked to peripheral artery disease (PAD), endothelial senescence, and vascular aging. Emerging evidence showed the beneficial role of probiotics and prebiotics in the management of several atherogenic risk factors through the remodeling of the gut microbiota, thus leading to a reduction in TMAO levels and atherosclerotic lesions. Despite the promising outcomes in different studies, the definite mechanisms of gut dysbiosis and microbiota-derived TMAO involved in atherosclerosis remain not fully understood. More studies are still required to focus on the molecular mechanisms and precise treatments targeting gut microbiota and leading to atheroprotective effects.
Topics: Animals; Humans; Aged; Gastrointestinal Microbiome; Dysbiosis; Methylamines; Atherosclerosis; Aging
PubMed: 36768722
DOI: 10.3390/ijms24032399 -
International Journal of Medical... 2023Atherosclerosis is a chronic, inflammatory disease characterized by a lipid-driven infiltration of inflammatory cells in large and medium arteries and is considered to...
Atherosclerosis is a chronic, inflammatory disease characterized by a lipid-driven infiltration of inflammatory cells in large and medium arteries and is considered to be a major underlying cause of cardiovascular diseases. Cuproptosis, a novel form of cell death, is highly linked to mitochondrial metabolism and mediated by protein lipoylation. However, the clinical implication of cuproptosis-related genes (CRGs) in atherosclerosis remains unclear. In this study, genes collected from the GEO database intersected with CRGs were identified in atherosclerosis. GSEA, GO and KEGG pathway enrichment analyses were performed for functional annotation. Through the random forest algorithm and the construction of a protein-protein interaction (PPI) network, eight selected genes (LOXL2, SLC31A1, ATP7A, SLC31A2, COA6, UBE2D1, CP and SOD1) and a vital cuproptosis-related gene FDX1 were then further validated. Two independent datasets (GSE28829 (N = 29), GSE100927 (N = 104)) were collected to construct the signature of CRGs for validation in atherosclerosis. Consistently, the atherosclerosis plaques showed significantly higher expression of SLC31A1, SLC31A2 and lower expression of SOD1 than the normal intimae. The area under the curve (AUC) of SLC31A1, SLC31A2 and SOD1 performed well for the diagnostic validation in the two datasets. In conclusion, the cuproptosis-related gene signature could serve as a potential diagnostic biomarker for atherosclerosis and may offer novel insights into the treatment of cardiovascular diseases. Based on the hub genes, a competing endogenous RNA (ceRNA) network of lncRNA-miRNA-mRNA and a transcription factor regulation network were ultimately constructed to explore the possible regulatory mechanism in atherosclerosis.
Topics: Humans; Atherosclerosis; Biomarkers; Cardiovascular Diseases; Carrier Proteins; Mitochondrial Proteins; Plaque, Atherosclerotic; Superoxide Dismutase-1; Copper; Apoptosis
PubMed: 37324184
DOI: 10.7150/ijms.83009