Lipoprotein(a) in Atherosclerotic Diseases: From Pathophysiology to Diagnosis and Treatment

Molecules, Journal Year: 2023, Volume and Issue: 28(3), P. 969 - 969

Published: Jan. 18, 2023

Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL) cholesterol-like particle bound to apolipoprotein(a). Increased Lp(a) levels are an independent, heritable causal risk factor for atherosclerotic cardiovascular disease (ASCVD) as they largely determined by variations in the gene (LPA) locus encoding apo(a). preferential carrier oxidized phospholipids (OxPL), and its role adversely affects vascular inflammation, lesions, endothelial function thrombogenicity, which pathophysiologically leads (CV) events. Despite this crucial of Lp(a), measurement lacks globally unified method, and, between different laboratories, results need standardization. Standard antilipidemic therapies, such statins, fibrates ezetimibe, have mediocre effect on levels, although it not yet clear whether treatments can affect CV events prognosis. This narrative review aims summarize knowledge regarding mechanisms mediating atherosclerosis thrombosis discuss current diagnostic therapeutic potentials.

Language: Английский

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Pollution from fine particulate matter and atherosclerosis: A narrative review

Environment International, Journal Year: 2023, Volume and Issue: 175, P. 107923 - 107923

Published: April 10, 2023

According to the WHO, entire global population is exposed air pollution levels higher than recommended for health preservation. Air a complex mixture of nano- micro-sized particles and gaseous components that poses major threat public health. Among most important pollutants, causal associations have been established between particulate matter (PM), mainly < 2.5 μm, cardiovascular diseases (CVD), i.e., hypertension, coronary artery disease, ischemic stroke, congestive heart failure, arrhythmias as well total mortality. Aim this narrative review describe critically discuss proatherogenic effects PM2.5 attributed many direct or indirect comprising endothelial dysfunction, chronic low-grade inflammatory state, increased production reactive oxygen species, mitochondrial dysfunction activation metalloproteases, all leading unstable arterial plaques. Higher concentrations pollutants are associated with presence vulnerable plaques plaque ruptures witnessing instability. often disregarded CVD risk factor, in spite fact it one main modifiable factors relevant prevention management CVD. Thus, not only structural actions should be taken order mitigate emissions, but professionals also take care counsel patients on risks pollution.

Language: Английский

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Hypercholesterolemia and inflammation—Cooperative cardiovascular risk factors

European Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 6, 2024

Abstract Background Maintaining low concentrations of plasma low‐density lipoprotein cholesterol (LDLc) over time decreases the number LDL particles trapped within artery wall, slows progression atherosclerosis and delays age at which mature atherosclerotic plaques develop. This substantially reduces lifetime risk cardiovascular disease (ASCVD) events. In this context, plaque development vulnerability result not only from lipid accumulation but also inflammation. Results Changes in composition immune cells, including macrophages, dendritic T B mast cells neutrophils, along with altered cytokine chemokine release, disrupt equilibrium between inflammation anti‐inflammatory mechanisms sites. Considering that it is a competition LDLc inflammation, instead they are partners crime, present narrative review aims to give an overview main inflammatory molecular pathways linked raised describe impact lipid‐lowering approaches on burden. Although remarkable changes driven by most recent lowering combinations, relative reduction C‐reactive protein appears be independent magnitude lowering. Conclusion Identifying clinical biomarkers (e.g. interleukin‐6) possible targets for therapy holds promise monitoring reducing ASCVD burden suitable patients.

Language: Английский

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Exploring the role of epicardial adipose-tissue-derived extracellular vesicles in cardiovascular diseases

iScience, Journal Year: 2024, Volume and Issue: 27(4), P. 109359 - 109359

Published: Feb. 29, 2024

Epicardial adipose tissue (EAT) is a fat depot located between the myocardium and visceral layer of epicardium, which, owing to its location, can influence surrounding tissues act as local transducer systemic inflammation. The mechanisms upon which such depends on are however unclear. Given role EAT undoubtedly has in scheme cardiovascular diseases (CVDs), understanding impact cellular components upmost importance. Extracellular vesicles (EVs) constitute promising candidates fill gap knowledge concerning unexplored through promotes onset progression CVDs. Owing their ability transporting active biomolecules, EAT-derived EVs have been reported be actively involved pathogenesis ischemia/reperfusion injury, coronary atherosclerosis, heart failure, atrial fibrillation. Exploring precise functions exert this context may aid connecting dots

Language: Английский

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Emerging role of exosomes in vascular diseases

Frontiers in Cardiovascular Medicine, Journal Year: 2023, Volume and Issue: 10

Published: March 2, 2023

Exosomes are biological small spherical lipid bilayer vesicles secreted by most cells in the body. Their contents include nucleic acids, proteins, and lipids. can transfer material molecules between consequently have a variety of functions, participating disease development while exhibiting potential value as biomarkers therapeutics. Growing evidence suggests that exosomes vital mediators vascular remodeling. Endothelial (ECs), smooth muscle (VSMCs), inflammatory cells, adventitial fibroblasts (AFs) communicate through exosomes; such communication is associated with responses, cell migration proliferation, metabolism, leading to changes function structure. Essential hypertension (EH), atherosclerosis (AS), pulmonary arterial (PAH) common diseases significant This paper reviews latest research progress on involvement remodeling intercellular information exchange provides new ideas for understanding related diseases.

Language: Английский

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Identification and validation of PCSK9 as a prognostic and immune-related influencing factor in tumorigenesis: a pan-cancer analysis

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: Oct. 4, 2023

Proprotein convertase subtilisin/kexin-9 (PCSK9) has been primarily studied in the cardiovascular field however, its role cancer pathophysiology remains incompletely defined. Recently, a pivotal for PCSK9 immunotherapy was proposed based on finding that inhibition associated with enhancing antigen presentation efficacy of target programmed cell death-1 (PD-1). Herein, we provide results comprehensive pan-cancer analysis assessed prognostic and immunological functions cancer.Using variety available online cancer-related databases including TIMER, cBioPortal, GEPIA, identified abnormal expression potential clinical associations diverse types liver, brain lung. We also validated progression-free survival (PFS) immune infiltration neuroblastoma.Overall, revealed an association between dysregulated poor outcomes various types. Specifically, extensively genetically altered across most consistently found different tumor substages when compared adjacent normal tissues. Thus, aberrant DNA methylation may be responsible many Focusing liver hepatocellular carcinoma (LIHC), correlated clinicopathological characteristics following stratified analyses. significantly infiltrate since specific markers CD8+ T cells, macrophage polarization, exhausted cells exhibited PCSK9-related patterns LIHC lung squamous carcinoma. In addition, connected resistance drugs such as erlotinib docetaxel. Finally, neuroblastoma samples concluded appeared to correlate PFS natural killer patients.PCSK9 could serve robust biomarker given correlation infiltrates types, thus potentially highlighting new direction targeted therapy cancers.

Language: Английский

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Microstructured soft devices for the growth and analysis of populations of homogenous multicellular tumor spheroids

Cellular and Molecular Life Sciences, Journal Year: 2023, Volume and Issue: 80(4)

Published: March 16, 2023

Multicellular tumor spheroids are rapidly emerging as an improved in vitro model with respect to more traditional 2D culturing. Microwell culturing is a simple and accessible method for generating large number of uniformly sized spheroids, but commercially available systems often do not enable researchers perform complete analysis pipelines the mechanical properties their culture environment commonly matching those target tissue. We herein report obtain custom-designed self-built microwell arrays made polydimethylsiloxane or agarose uniform 3D cell structure generation. Such materials can provide tunable flexibility. developed protocols variety cancer non-cancer lines such devices molecular imaging characterizations spheroid growth, viability, response pharmacological treatments. Hundreds grow (in scaffolded scaffold-free conditions) at homogeneous rates be harvested will. Microscopy performed situ during end culture. Fluorescence (confocal) microscopy after staining while retaining geographic arrangement plate wells. This platform statistically robust investigations on biology screening drug

Language: Английский

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Proteomics and Lipidomics to unveil the contribution of PCSK9 beyond cholesterol lowering: a narrative review

Frontiers in Cardiovascular Medicine, Journal Year: 2023, Volume and Issue: 10

Published: June 12, 2023

Proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the key regulators low-density lipoprotein receptor (LDLR), can play a direct role in atheroma development. Although advances understandings genetic PCSK9 polymorphisms have enabled to reveal complex pathophysiology cardiovascular diseases (CVDs), increasing lines evidence support non-cholesterol-related processes mediated by PCSK9. Owing major improvements mass spectrometry-based technologies, multimarker proteomic and lipidomic panels hold promise identify novel lipids proteins potentially related Within this context, narrative review aims provide an overview most significant proteomics lipidomics studies effects beyond cholesterol lowering. These approaches unveil non-common targets PCSK9, leading development statistical models for CVD risk prediction. Finally, era precision medicine, we reported impact on extracellular vesicles (EVs) composition, effect that could contribute increased prothrombotic status patients. The possibility modulate EVs release cargo help counteract progression atherosclerotic process.

Language: Английский

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PCSK9 activation promotes early atherosclerosis in a vascular microphysiological system

APL Bioengineering, Journal Year: 2023, Volume and Issue: 7(4)

Published: Oct. 16, 2023

Atherosclerosis is a primary precursor of cardiovascular disease (CVD), the leading cause death worldwide. While proprotein convertase subtilisin/kexin 9 (PCSK9) contributes to CVD by degrading low-density lipoprotein receptors (LDLR) and altering lipid metabolism, PCSK9 also influences vascular inflammation, further promoting atherosclerosis. Here, we utilized microphysiological system test effect activation or repression on initiation atherosclerosis screen efficacy small molecule inhibitor. We have generated over-expressed (P+) repressed (P−) human induced pluripotent stem cells (iPSCs) differentiated them smooth muscle (viSMCs) endothelial (viECs). Tissue-engineered blood vessels (TEBVs) made from P+ viSMCs viECs resulted in increased monocyte adhesion compared wild type (WT) P− equivalents when treated with enzyme-modified LDL (eLDL) TNF-α. found significant viEC dysfunction, such as secretion VCAM-1, TNF-α, IL-6, eLDL A compound, NYX-1492, that was originally designed block binding LDLR tested TEBVs determine its lowering PCSK9-induced inflammation. The compound reduced evidence VCAM-1 These results suggest inhibition may decrease inflammation addition plasma levels, enhancing anti-atherosclerotic effects, particularly patients elevated chronic

Language: Английский

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Mitochondrial function in patients affected with fibromyalgia syndrome is impaired and correlates with disease severity

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: July 26, 2024

Fibromyalgia is a musculoskeletal syndrome characterized by chronic widespread pain that often associated with systemic manifestations. Since mitochondria are the main source of cellular energy, we hypothesized fibromyalgia could be linked to mitochondrial impairment. Aim was study dysfunction in peripheral blood mononuclear cells isolated from 50 patients primary and 10 apparently healthy controls. Although no differences basal respiration were observed between controls, lower median bioenergetic health index (BHI; -22.4%, p = 0.03), proxy function, found patients. According severity score (FSS), composite symptom scale, BHI (-18.7%) FS ≥ 20 compared those FSS < 20. Negative moderate correlations only (r= -0.36) -0.38). We demonstrated had an impaired function. Additionally, mild correlation BHI, possibly indicating altered these patients, narrows rather than central nervous system involvement.

Language: Английский

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