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World Journal of Experimental Medicine Jun 2024Aortic aneurysm (AA) refers to the persistent dilatation of the aorta, exceeding three centimeters. Investigating the pathophysiology of this condition is important for... (Review)
Review
Aortic aneurysm (AA) refers to the persistent dilatation of the aorta, exceeding three centimeters. Investigating the pathophysiology of this condition is important for its prevention and management, given its responsibility for more than 25000 deaths in the United States. AAs are classified based on their location or morphology. various pathophysiologic pathways including inflammation, the immune system and atherosclerosis have been implicated in its development. Inflammatory markers such as transforming growth factor β, interleukin-1β, tumor necrosis factor-α, matrix metalloproteinase-2 and many more may contribute to this phenomenon. Several genetic disorders such as Marfan syndrome, Ehler-Danlos syndrome and Loeys-Dietz syndrome have also been associated with this disease. Recent years has seen the investigation of novel management of AA, exploring the implication of different immune suppressors, the role of radiation in shrinkage and prevention, as well as minimally invasive and newly hypothesized surgical methods. In this narrative review, we aim to present the new contributing factors involved in pathophysiology of AA. We also highlighted the novel management methods that have demonstrated promising benefits in clinical outcomes of the AA.
PubMed: 38948412
DOI: 10.5493/wjem.v14.i2.91408 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024As a member of the tumor necrosis factor receptor family, osteoprotegerin (OPG) is highly expressed in adults in the lung, heart, kidney, liver, spleen, thymus,... (Review)
Review
As a member of the tumor necrosis factor receptor family, osteoprotegerin (OPG) is highly expressed in adults in the lung, heart, kidney, liver, spleen, thymus, prostate, ovary, small intestines, thyroid gland, lymph nodes, trachea, adrenal gland, the testis, and bone marrow. Together with the receptor activator of nuclear factor-κB (RANK) and the receptor activator of nuclear factor-κB ligand (RANKL), it forms the RANK/RANKL/OPG pathway, which plays an important role in the molecular mechanism of the development of various diseases. MicroRNAs (miRNAs) are a class of endogenous non-coding RNAs performing regulatory functions in eukaryotes, with a size of about 20-25 nucleotides. miRNA genes are transcribed into primary transcripts by RNA polymerase, bind to RNA-induced silencing complexes, identify target mRNAs through complementary base pairing, with a single miRNA being capable of targeting hundreds of mRNAs, and influence the expression of many genes through pathways involved in functional interactions. In recent years, a large number of studies have been done to explore the mechanism of action of miRNA in diseases through miRNA isolation, miRNA quantification, miRNA spectrum analysis, miRNA target detection, and regulation of miRNA levels, and other technologies. It was found that miRNA can play a key role in the pathogenesis of osteoporosis, rheumatoid arthritis, and other diseases by targeting OPG. The purpose of this review is to explore the interaction between miRNA and OPG in various diseases, and to propose new ideas for studying the mechanism of action of OPG in diseases.
Topics: Osteoprotegerin; Humans; MicroRNAs; Receptor Activator of Nuclear Factor-kappa B; RANK Ligand; Neoplasms; Animals; Signal Transduction; Arthritis, Rheumatoid
PubMed: 38948285
DOI: 10.12182/20240560607 -
Cancer Innovation Aug 2024Clinical studies have shown that atherosclerotic cardiovascular disease and cancer often co-exist in the same individual. The present study aimed to investigate the role...
BACKGROUND
Clinical studies have shown that atherosclerotic cardiovascular disease and cancer often co-exist in the same individual. The present study aimed to investigate the role of high-fat-diet (HFD)-induced obesity in the coexistence of the two diseases and the underlying mechanism in apolipoprotein E-knockout (ApoE) mice.
METHODS
Male ApoE mice were fed with a HFD or a normal diet (ND) for 15 weeks. On the first day of Week 13, the mice were inoculated subcutaneously in the right axilla with Lewis lung cancer cells. At Weeks 12 and 15, serum lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and vascular endothelial growth factor levels were measured by enzyme-linked immunosorbent assay, and blood monocytes and macrophages were measured by fluorescence-activated cell sorting. At Week 15, the volume and weight of the local subcutaneous lung cancer and metastatic lung cancer and the amount of aortic atherosclerosis were measured.
RESULTS
At Week 15, compared with mice in the ND group, those in the HFD group had a larger volume of local subcutaneous cancer ( = 0.0004), heavier tumors ( = 0.0235), more metastatic cancer in the lungs ( < 0.0001), a larger area of lung involved in metastatic cancer ( = 0.0031), and larger areas of atherosclerosis in the aorta ( < 0.0001). At Week 12, serum LOX-1, serum vascular endothelial growth factor, and proportions of blood monocytes and macrophages were significantly higher in the HFD group than those in the ND group ( = 0.0002, = 0.0029, = 0.0480, and = 0.0106, respectively); this trend persisted until Week 15 ( = 0.0014, = 0.0012, = 0.0001, and = 0.0204).
CONCLUSIONS
In this study, HFD-induced obesity could simultaneously promote progression of lung cancer and atherosclerosis in the same mouse. HFD-induced upregulation of LOX-1 may play an important role in the simultaneous progression of these two conditions via the inflammatory response and VEGF.
PubMed: 38948249
DOI: 10.1002/cai2.127 -
MLife Jun 2024Atherosclerosis is a chronic inflammatory metabolic disease with a complex pathogenesis. However, the exact details of its pathogenesis are still unclear, which limits... (Review)
Review
Atherosclerosis is a chronic inflammatory metabolic disease with a complex pathogenesis. However, the exact details of its pathogenesis are still unclear, which limits effective clinical treatment of atherosclerosis. Recently, multiple studies have demonstrated that the gut microbiota plays a pivotal role in the onset and progression of atherosclerosis. This review discusses possible treatments for atherosclerosis using the gut microbiome as an intervention target and summarizes the role of the gut microbiome and its metabolites in the development of atherosclerosis. New strategies for the treatment of atherosclerosis are needed. This review provides clues for further research on the mechanisms of the relationship between the gut microbiota and atherosclerosis.
PubMed: 38948150
DOI: 10.1002/mlf2.12110 -
Cancer Innovation Jun 2024Histone deacetylase 6 (HDAC6) belongs to a class of epigenetic targets that have been found to be a key protein in the association between tumors and cardiovascular... (Review)
Review
Histone deacetylase 6 (HDAC6) belongs to a class of epigenetic targets that have been found to be a key protein in the association between tumors and cardiovascular disease. Recent studies have focused on the crucial role of HDAC6 in regulating cardiovascular diseases such as atherosclerosis, myocardial infarction, myocardial hypertrophy, myocardial fibrosis, hypertension, pulmonary hypertension, and arrhythmia. Here, we review the association between HDAC6 and cardiovascular disease, the research progress of HDAC6 inhibitors in the treatment of cardiovascular disease, and discuss the feasibility of combining HDAC6 inhibitors with other therapeutic agents to treat cardiovascular disease.
PubMed: 38947757
DOI: 10.1002/cai2.114 -
Cureus May 2024Advanced glycation end products (AGEs) accumulate in the brain, leading to neurodegenerative conditions such as Alzheimer's disease (AD). The pathophysiology of AD is... (Review)
Review
Advanced glycation end products (AGEs) accumulate in the brain, leading to neurodegenerative conditions such as Alzheimer's disease (AD). The pathophysiology of AD is influenced by receptors for AGEs and toll-like receptor 4 (TLR4). Protein glycation results in irreversible AGEs through a complicated series of reactions involving the formation of Schiff's base, the Amadori reaction, followed by the Maillard reaction, which causes abnormal brain glucose metabolism, oxidative stress, malfunctioning mitochondria, plaque deposition, and neuronal death. Amyloid plaque and other stimuli activate macrophages, which are crucial immune cells in AD development, triggering the production of inflammatory molecules and contributing to the disease's pathogenesis. The risk of AD is doubled by risk factors for atherosclerosis, dementia, advanced age, and type 2 diabetic mellitus (DM). As individuals age, the prevalence of neurological illnesses such as AD increases due to a decrease in glyoxalase levels and an increase in AGE accumulation. Insulin's role in proteostasis influences hallmarks of AD-like tau phosphorylation and amyloid β peptide clearance, affecting lipid metabolism, inflammation, vasoreactivity, and vascular function. The high-mobility group box 1 (HMGB1) protein, a key initiator and activator of a neuroinflammatory response, has been linked to the development of neurodegenerative diseases such as AD. The TLR4 inhibitor was found to improve memory and learning impairment and decrease Aβ build-up. Therapeutic research into anti-glycation agents, receptor for advanced glycation end products (RAGE) inhibitors, and AGE breakers offers hope for intervention strategies. Dietary and lifestyle modifications can also slow AD progression. Newer therapeutic approaches targeting AGE-related pathways are needed.
PubMed: 38947632
DOI: 10.7759/cureus.61373 -
Cureus May 2024Coronary artery disease continues to remain the leading cause of mortality worldwide. Coronary blood supply is provided through the right and left main coronary...
Coronary artery disease continues to remain the leading cause of mortality worldwide. Coronary blood supply is provided through the right and left main coronary arteries. The left main coronary artery (LMCA) in turn gives rise to the left anterior descending (LAD) and left circumflex (LCX) arteries. In some cases, LMCA may trifurcate into the ramus intermedius (RI) in addition to the LAD and LCX arteries. Atherosclerotic plaque formation and rupture with subsequent clot formation and occlusion of coronary arteries are the underlying mechanisms of myocardial infarction. Though the clinical implications of the presence of ramus intermedius (RI) are controversial some data suggest that the RI is associated with an increased risk of atherosclerotic plaque formation in the LMCA and the proximal LAD. Conversely, it has been proposed that the RI provides an additional collateral source of blood supply to the myocardium and may potentially contribute to improved survival. Case reports tout the benefits of RI, specifically in the setting of multivessel coronary artery occlusions. Whether it increases the risk of atherosclerotic plaque formation or whether it is protective has yet to be determined. We present a case of a 58-year-old male who presented with acute coronary syndrome and cardiogenic shock due to total ostial occlusion of LAD. The patient had also chronic total occlusions of the right coronary artery and LCX but a patent RI, which was the only source of blood supply to the myocardium and practically determined the patient's survival. Additionally, we performed a literature review to identify similar cases, to support RI's potentially protective role in enhancing survival.
PubMed: 38947610
DOI: 10.7759/cureus.61288 -
Heliyon Jun 2024Exserolides are isocoumarin derivatives containing lactone moiety. Recently, some isocoumarins have been demonstrated to ameliorate hyperlipidemia, a major factor for...
Exserolides are isocoumarin derivatives containing lactone moiety. Recently, some isocoumarins have been demonstrated to ameliorate hyperlipidemia, a major factor for inducing cardiovascular diseases. However, the effects and mechanisms of action of exserolides on hyperlipidemia are not known. The aim of this study is to investigate whether the marine fungus sp.-derived exserolides (compounds I, J, E, and F) exert lipid-lowering effects via improving reverse cholesterol transport (RCT) . RAW264.7 macrophages and HepG2 cells were used to establish lipid-laden models, and the levels of intracellular lipids and RCT-related proteins were determined by assay kits and Western blotting, respectively. We observed that exserolides (at a 5 μM concentration) significantly decreased intracellular cholesterol and triglyceride levels in oxidized low-density lipoprotein-laden RAW264.7 cells and markedly improved [H]-cholesterol efflux. Among the four tested compounds, exserolide J increased the protein levels of ATP-binding cassette transporter A1, peroxisome proliferator-activated receptor α (PPARα), and liver X receptor α (LXRα). Furthermore, treatment with exserolides significantly decreased oleic acid-laden lipid accumulation in HepG2 hepatocytes. Mechanistically, exserolides enhance PPARα protein levels; furthermore, compound J increases cholesterol 7 alpha-hydroxylase A1 and LXRα protein levels. Molecular docking revealed that exserolides, particularly compound J, can interact with PPARα and LXRα proteins. These data suggest that the terminal carboxyl group of compound J plays a key role in lowering lipid levels by stimulating LXRα and PPARα proteins. In conclusion, compound J exhibits powerful lipid-lowering effects . However, its hypolipidemic effects should be investigated in the future.
PubMed: 38947487
DOI: 10.1016/j.heliyon.2024.e31861 -
Research Square Jun 2024Coronary artery calcium (CAC) scans contain valuable information beyond the Agatston Score which is currently reported for predicting coronary heart disease (CHD) only....
AI-enabled Cardiac Chambers Volumetry and Calcified Plaque Characterization in Coronary Artery Calcium (CAC) Scans (AI-CAC) Significantly Improves on Agatston CAC Score for Predicting All Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis.
Coronary artery calcium (CAC) scans contain valuable information beyond the Agatston Score which is currently reported for predicting coronary heart disease (CHD) only. We examined whether new artificial intelligence (AI) algorithms applied to CAC scans may provide significant improvement in prediction of all cardiovascular disease (CVD) events in addition to CHD, including heart failure, atrial fibrillation, stroke, resuscitated cardiac arrest, and all CVD-related deaths. We applied AI-enabled automated cardiac chambers volumetry and automated calcified plaque characterization to CAC scans (AI-CAC) of 5830 individuals (52.2% women, age 61.7±10.2 years) without known CVD that were previously obtained for CAC scoring at the baseline examination of the Multi-Ethnic Study of Atherosclerosis (MESA). We used 15-year outcomes data and assessed discrimination using the time-dependent area under the curve (AUC) for AI-CAC versus the Agatston Score. During 15 years of follow-up, 1773 CVD events accrued. The AUC at 1-, 5-, 10-, and 15-year follow up for AI-CAC vs Agatston Score was (0.784 vs 0.701), (0.771 vs. 0.709), (0.789 vs.0.712) and (0.816 vs. 0.729) (p<0.0001 for all), respectively. The category-free Net Reclassification Index of AI-CAC vs. Agatston Score at 1-, 5-, 10-, and 15-year follow up was 0.31, 0.24, 0.29 and 0.29 (p<.0001 for all), respectively. AI-CAC plaque characteristics including number, location, and density of plaque plus number of vessels significantly improved NRI for CAC 1-100 cohort vs. Agatston Score (0.342). In this multi-ethnic longitudinal population study, AI-CAC significantly and consistently improved the prediction of all CVD events over 15 years compared with the Agatston score.
PubMed: 38947043
DOI: 10.21203/rs.3.rs-4433105/v1 -
World Journal of Clinical Oncology Jun 2024Myeloproliferative neoplasms (MPNs) occur due to the abnormal proliferation of one or more terminal myeloid cell lines in peripheral blood. Subjects suffering from MPNs... (Review)
Review
Myeloproliferative neoplasms (MPNs) occur due to the abnormal proliferation of one or more terminal myeloid cell lines in peripheral blood. Subjects suffering from MPNs display a high burden of cardiovascular risk factors, and thrombotic events are often the cause of death in this population of patients. Herein, we provide a brief overview of dyslipidemia and metabolic syndrome and their epidemiology in MPNs and examine the common molecular mechanisms between dyslipidemia, metabolic syndrome, and MPNs, with a special focus on cardiovascular risk, atherosclerosis, and thrombotic events. Furthermore, we investigate the impact of dyslipidemia and metabolic syndrome on the occurrence and survival of thrombosis in MPN patients, as well as the management of dyslipidemia in MPNs, and the impact of MPN treatment on serum lipid concentrations, particularly as side/adverse effects reported in the context of clinical trials.
PubMed: 38946827
DOI: 10.5306/wjco.v15.i6.717