Evolving concepts of low‐density lipoprotein: From structure to function

European Journal of Clinical Investigation, Journal Year: 2025, Volume and Issue: unknown

Published: March 5, 2025

Low-density lipoprotein (LDL) is a central player in atherogenesis and has long been referred to as 'bad cholesterol.' However, emerging evidence indicates that LDL functions multifaceted ways beyond cholesterol transport include roles inflammation, immunity, cellular signaling. Understanding LDL's structure, metabolism function essential for advancing cardiovascular disease research therapeutic strategies. This narrative review examines the history, structural properties, of health disease. We analyze key milestones research, from its early identification recent advancements molecular biology omics-based investigations. Structural functional insights are explored through imaging, proteomic analyses lipidomic profiling, providing deeper understanding heterogeneity. metabolism, biosynthesis receptor-mediated clearance, plays crucial role lipid homeostasis atherogenesis. Beyond transport, contributes plaque modulates adaptive immunity regulates signaling pathways. studies reveal heterogeneous composition, which influences pathogenic potential. Evolving perspectives on redefine clinical significance, affecting risk assessment interventions. A holistic challenges traditional underscores complexity health. Future should focus further elucidating diversity refine prediction models strategies, ultimately improving outcomes.

Language: Английский

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Therapeutic and pharmacological applications of extracellular vesicles and lipoproteins

British Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 181(23), P. 4733 - 4749

Published: Sept. 20, 2024

Abstract In recent years, various approaches have been undertaken to eliminate lipoproteins co‐isolated with extracellular vesicles, as they were initially regarded contaminating entities. However, novel discoveries are reshaping our perspective. body fluids, these distinct particles not only co‐exist, but also interactions between them likely occur. Extracellular vesicles and can associate each other, share cargo, influence other's functions, jointly a role in the pathomechanisms of diseases. Additionally, their association carries important implications for therapeutic pharmacological aspects lipid‐lowering strategies. lipoprotein may roles elimination other from circulation. The objective this minireview is delve into aspects. Here, we show that under certain physiological pathological conditions, ‘partners’ rather than ‘strangers’ or ‘rivals’.

Language: Английский

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The Emerging Role of PCSK9 in the Pathogenesis of Alzheimer’s Disease: A Possible Target for the Disease Treatment

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13637 - 13637

Published: Dec. 20, 2024

Alzheimer’s disease (AD) is a multifactorial neurodegenerative mainly caused by β-amyloid (Aβ) accumulation in the brain. Among several factors that may concur to AD development, elevated cholesterol levels and brain dyshomeostasis have been recognized play relevant role. Proprotein convertase subtilisin/kexin type 9 (PCSK9) protein primarily known regulate plasma low-density lipoproteins (LDLs) rich be one of main causes familial hypercholesterolemia. In addition that, PCSK9 also carry out diverse important activities brain, including control neuronal differentiation, apoptosis, and, importantly, LDL receptors functionality. Moreover, appeared directly involved some principal processes responsible for such as inflammation, oxidative stress, Aβ deposition. On these bases, management might represent promising approach treatment. The purpose this review elucidate role PCSK9, whether or not cholesterol-related, pathogenesis give an updated overview most innovative therapeutic strategies developed so far counteract pleiotropic both humoral focusing particular on their potentiality management.

Language: Английский

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Natural phytochemicals as small-molecule proprotein convertase subtilisin/kexin type 9 inhibitors

Tzu Chi Medical Journal, Journal Year: 2024, Volume and Issue: 36(4), P. 360 - 369

Published: Sept. 5, 2024

A decrease in the levels of low-density lipoprotein receptors (LDLRs) leads to accumulation LDL cholesterol (LDL-C) bloodstream, resulting hypercholesterolemia and atherosclerotic cardiovascular diseases. Increasing expression level or inducing activity LDLR hepatocytes can effectively control hypercholesterolemia. Proprotein convertase subtilisin/kexin type 9 (PCSK9) protein, primarily produced liver, promotes degradation LDLR. Inhibiting and/or function PCSK9 increase on surface promote LDL-C clearance from plasma. Thus, targeting represents a new strategy for developing preventive therapeutic interventions Currently, monoclonal antibodies are used as inhibitors clinical practice. However, need oral affordable anti-PCSK9 medications limits perspective choosing usage. Emerging research reports have demonstrated that natural phytochemicals efficacy maintaining stability regulating lipid metabolism. Developing novel phytochemical serve starting point small-molecule drugs reduce plasma patients. In this review, we summarize current literature critical role controlling hypercholesterolemia, discuss results studies attempting develop inhibitors, with an emphasis inhibitory effects PCSK9. Furthermore, provide insight into mechanisms action by which reported exert their potential against

Language: Английский

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Revolutionizing Medicine: Harnessing Plant-Derived Vesicles for Therapy and Drug Transport

Heliyon, Journal Year: 2024, Volume and Issue: 10(22), P. e40127 - e40127

Published: Nov. 1, 2024

Language: Английский

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