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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 -
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 -
Arteriosclerosis, Thrombosis, and... Sep 2020Despite major advances in the primary and secondary prevention of atherosclerosis and its risk factors, atherosclerotic cardiovascular disease remains a major clinical... (Review)
Review
Despite major advances in the primary and secondary prevention of atherosclerosis and its risk factors, atherosclerotic cardiovascular disease remains a major clinical and financial burden on individuals and health systems worldwide. In addition, neointima formation and proliferation due to mechanical trauma to the vessel wall during percutaneous coronary interventions can lead to vascular restenosis and limit the longevity and effectiveness of coronary revascularization. Long noncoding RNAs (lncRNAs) have emerged as a novel class of epigenetic regulators with critical roles in the pathogenesis of atherosclerosis and restenosis following vascular injury. Here, we provide an in-depth review of lncRNAs that regulate the development of atherosclerosis or contribute to the pathogenesis of restenosis following mechanical vascular injury. We describe the diverse array of intracellular mechanisms by which lncRNAs exert their regulatory effects. We highlight the utility and challenges of lncRNAs as biomarkers. Finally, we discuss the immense translational potential of lncRNAs and strategies for targeting them therapeutically using oligonucleotide-based therapeutics and novel gene therapy platforms.
Topics: Animals; Arteries; Atherosclerosis; Constriction, Pathologic; Epigenesis, Genetic; Genetic Markers; Humans; Oligonucleotides, Antisense; Plaque, Atherosclerotic; RNA, Long Noncoding; RNAi Therapeutics; Signal Transduction; Vascular Remodeling; Vascular System Injuries
PubMed: 32698685
DOI: 10.1161/ATVBAHA.120.314222 -
American Journal of Physiology. Heart... Nov 2019Cardiovascular disease (CVD) is the leading cause of death worldwide. The human body is populated by a diverse community of microbes, dominated by bacteria, but also... (Review)
Review
Cardiovascular disease (CVD) is the leading cause of death worldwide. The human body is populated by a diverse community of microbes, dominated by bacteria, but also including viruses and fungi. The largest and most complex of these communities is located in the gastrointestinal system and, with its associated genome, is known as the gut microbiome. Gut microbiome perturbations and related dysbiosis have been implicated in the progression and pathogenesis of CVD, including atherosclerosis, hypertension, and heart failure. Although there have been advances in the characterization and analysis of the gut microbiota and associated bacterial metabolites, the exact mechanisms through which they exert their action are not well understood. This review will focus on the role of the gut microbiome and associated functional components in the development and progression of atherosclerosis. Potential treatments to alter the gut microbiome to prevent or treat atherosclerosis and CVD are also discussed.
Topics: Animals; Anti-Bacterial Agents; Arteries; Atherosclerosis; Bacteria; Diet, Healthy; Dietary Supplements; Dysbiosis; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Host-Pathogen Interactions; Humans; Intestines; Plaque, Atherosclerotic; Signal Transduction
PubMed: 31469291
DOI: 10.1152/ajpheart.00376.2019 -
Cells Sep 2020Atherosclerosis is an age-related disorder associated with long-term exposure to cardiovascular risk factors. The asymptomatic progression of atherosclerotic plaques... (Review)
Review
Atherosclerosis is an age-related disorder associated with long-term exposure to cardiovascular risk factors. The asymptomatic progression of atherosclerotic plaques leads to major cardiovascular diseases (CVD), including acute myocardial infarctions or cerebral ischemic strokes in some cases. Senescence, a biological process associated with progressive structural and functional deterioration of cells, tissues and organs, is intricately linked to age-related diseases. Cell senescence involves coordinated modifications in cellular compartments and has been demonstrated to contribute to different stages of atheroma development. Senescence-based therapeutic strategies are currently being pursued to treat and prevent CVD in humans in the near-future. In addition, distinct experimental settings allowed researchers to unravel potential approaches to regulate anti-apoptotic pathways, facilitate excessive senescent cell clearance and eventually reverse atherogenesis to improve cardiovascular function. However, a deeper knowledge is required to fully understand cellular senescence, to clarify senescence and atherogenesis intertwining, allowing researchers to establish more effective treatments and to reduce the cardiovascular disorders' burden. Here, we present an objective review of the key senescence-related alterations of the major intracellular organelles and analyze the role of relevant cell types for senescence and atherogenesis. In this context, we provide an updated analysis of therapeutic approaches, including clinically relevant experiments using senolytic drugs to counteract atherosclerosis.
Topics: Aging; Atherosclerosis; Cardiovascular Diseases; Cell Differentiation; Cellular Senescence; Humans; Organelles
PubMed: 32977446
DOI: 10.3390/cells9102146 -
Scientific Reports Apr 2020Cardiotrophin-1 (CT-1) is associated with cardiovascular (CV) diseases. We investigated the effect of CT-1 deficiency in the development and progression of...
Cardiotrophin-1 (CT-1) is associated with cardiovascular (CV) diseases. We investigated the effect of CT-1 deficiency in the development and progression of atherosclerosis in double knockout Apoect-1 mice. Apoe C57Bl/6 or Apoect-1 C57Bl/6 mice were fed a normal chow diet (NCD) or a high-cholesterol diet (HCD). After sacrifice, serum triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), free fatty acids and systemic paracrine factors were measured. Intraplaque lipid and collagen content were quantified in the aortic sections. Immune cell populations in spleen, lymph nodes and aorta were analysis by flow cytometry. Apoect-1 mice in accelerated atherosclerosis exhibited a reduction of total cholesterol, LDL-C, atherosclerotic plaques size in the aortic root and in the abdominal aorta and improved plaque stability in comparison to Apoe mice. CT-1 deficiency in Apoe mice on (HCD) promoted atheroprotective immune cell responses, as demonstrated by a rise in plasma anti-inflammatory immune cell populations (regulatory T cells, Tregs; regulatory B cells, Bregs and B1a cells) and atheroprotective IgM antibodies. CT-1 deficiency in advanced atherosclerosis mediated regulation of paracrine factors, such as interleukin (IL)-3, IL-6, IL-9, IL-15, IL-27, CXCL5, MCP-3, MIP-1α and MIP-1β. In a model of advanced atherosclerosis, CT-1 deficiency induced anti-inflammatory and atheroprotective effects which resulted in abrogation of atheroprogression.
Topics: Animals; Aorta; Apolipoproteins E; Atherosclerosis; Cytokines; Disease Models, Animal; Disease Progression; Gene Deletion; Male; Mice, Inbred C57BL
PubMed: 32238841
DOI: 10.1038/s41598-020-62596-6 -
International Journal of Molecular... Jan 2023Lipids are a complex group of molecules in the body, essential as structural, functional and metabolic components. When disbalanced, they are regarded as a... (Review)
Review
Lipids are a complex group of molecules in the body, essential as structural, functional and metabolic components. When disbalanced, they are regarded as a cardiovascular risk factor, traditionally in cholesterol level evaluation. However, due to their complex nature, much research is still needed for a comprehensive understanding of their role in atherosclerosis, especially in the young. Several new lipid biomarkers are emerging, some already researched to a point, such as lipoproteins and apolipoproteins. Other lipid molecules are also being increasingly researched, including oxidized forms due to oxidative inflammation in atherosclerosis, and sphingolipids. For many, even those less new, the atherogenic potential is not clear and no clinical recommendations are in place to aid the clinician in using them in everyday clinical practice. Moreover, lipids' involvement in atherogenesis in children has yet to be elucidated. This review summarizes the current knowledge on lipids as biomarkers of cardiovascular risk in the paediatric population.
Topics: Child; Humans; Lipids; Cardiovascular Diseases; Risk Factors; Atherosclerosis; Biomarkers; Heart Disease Risk Factors
PubMed: 36768558
DOI: 10.3390/ijms24032237 -
Frontiers in Endocrinology 2022The complications of macrovascular atherosclerosis are the leading cause of disability and mortality in patients with diabetes. It is generally believed that the... (Review)
Review
The complications of macrovascular atherosclerosis are the leading cause of disability and mortality in patients with diabetes. It is generally believed that the pathogenesis of diabetic vascular complications is initiated by the imbalance between injury and endogenous protective factors. Multiple endogenous protective factors secreted by endothelium, liver, skeletal muscle and other tissues are recognized of their importance in combating injury factors and maintaining the homeostasis of vasculatures in diabetes. Among them, glucagon-like peptide-1 based drugs were clinically proven to be effective and recommended as the first-line medicine for the treatment of type 2 diabetic patients with high risks or established arteriosclerotic cardiovascular disease (CVD). Some molecules such as irisin and lipoxins have recently been perceived as new protective factors on diabetic atherosclerosis, while the protective role of HDL has been reinterpreted since the failure of several clinical trials to raise HDL therapy on cardiovascular events. The current review aims to summarize systemic endogenous protective factors for diabetes-associated atherosclerosis and discuss their mechanisms and potential therapeutic strategy or their analogues. In particular, we focus on the existing barriers or obstacles that need to be overcome in developing new therapeutic approaches for macrovascular complications of diabetes.
Topics: Atherosclerosis; Diabetes Mellitus; Diabetic Angiopathies; Glucagon-Like Peptide 1; Humans; Protective Factors
PubMed: 35557850
DOI: 10.3389/fendo.2022.821028 -
International Journal of Molecular... Dec 2023Atherosclerosis is a complex and chronic inflammatory disease driven by multiple pathophysiological processes that are responsible for diverse cardiovascular events.... (Review)
Review
Atherosclerosis is a complex and chronic inflammatory disease driven by multiple pathophysiological processes that are responsible for diverse cardiovascular events. Atherosclerotic cardiovascular disease, despite substantial triumphs in primary and secondary prevention, remains a dominant epidemic that impairs human health. Therefore, deciphering the pathogenesis of atherosclerosis will provide a real‑world translational understanding. Homeobox cluster‑embedded antisense long non‑coding RNAs (HOX‑lncRNAs), a nascent class of lncRNA molecules with versatile roles in cancer, can also orchestrate various cell functions in cardiovascular disorders and have thus captured the attention of many researchers. Subsequently, numerous studies have demonstrated the role of HOX‑lncRNAs as potential modulators of atherosclerosis. Nevertheless, given that the understanding of HOX‑lncRNAs in atherosclerosis is only just emerging, ongoing research must be initiated to thoroughly pinpoint such causal roles. The present review aimed to highlight the important contributions of HOX‑lncRNAs to atherosclerosis and other pivotal biological processes related to cardiovascular disease. The review concludes with a discussion of the limitations, outlook, challenges and possible solutions associated with HOX‑lncRNAs in atherosclerosis. Looking forward, this may lead to extraordinary breakthroughs in revealing the molecular underpinnings of HOX‑lncRNAs and may offer a promising yet challenging landscape for robust therapeutic strategies for atherosclerosis and/or associated cardiovascular disorders.
Topics: Humans; Cardiovascular Diseases; RNA, Long Noncoding; Atherosclerosis; RNA, Antisense; DNA-Binding Proteins
PubMed: 37830159
DOI: 10.3892/ijmm.2023.5317