Primary hypercholesterolemia and development of cardiovascular disorders: Cellular and molecular mechanisms involved in low-grade systemic inflammation and endothelial dysfunction. (October 2021)

• Record Type: Journal Article
• Authors: Collado, Aida; Domingo, Elena; Piqueras, Laura; Sanz, Maria-Jesus
• Is Part Of: International journal of biochemistry & cell biology. Volume 139(2021)
• Publication Date: 2021-10
• Subjects: Akt protein kinase B -- Ang-II angiotensin-II -- apoB apolipoprotein B -- CAMs cell adhesion molecules -- CVD cardiovascular disease -- CX3CR1 fractalkine receptor -- ERK extracellular signal-regulated kinase -- FH familial hypercholesterolemia -- hs-CRP high sensitivity C reactive protein -- ICAM intercellular adhesion molecule -- IFNγ interferon γ -- IL interleukin -- IP-10 interferon γ-inducible protein-10 -- LDL low-density lipoprotein -- LDLR low-density lipoprotein receptor -- LGSI low-grade systemic inflammation -- mAb monoclonal antibody -- MAPK mitogen-activated protein kinase -- MCP-1 monocyte chemoattractant protein-1 -- MIP macrophage inflammatory protein -- Mon1/2/3 type 1/2/3 monocytes -- NADPH nicotinamide adenine dinucleotide phosphate -- NF nuclear factor -- Nox NADPH oxidase -- oxLDL oxidized low-density lipoprotein -- PCSK9 proprotein convertase subtilisin/kexin type 9 -- PF-4 platelet factor-4 -- PH primary hypercholesterolemia -- PI3K phosphatidylinositol 3-kinase -- RhoA Ras homolog family member A -- RIP receptor-interacting protein -- ROCK Rho-associated protein kinase -- ROS reactive oxygen species -- sCD40L soluble CD40 ligand -- SOD superoxide dismutase -- sP-selectin soluble P-selectin -- sTNFα soluble tumor necrosis factor α -- TC total cholesterol -- Th2/17 type 2/17 T helper lymphocytes -- TNFα tumor necrosis factor α -- TNFR tumor necrosis factor α receptor -- TRADD TNFR1-associated death domain protein -- TRAF TNF receptor-associated factor -- TRAIL TNF-related apoptosis-inducing ligand -- Treg regulatory T lymphocytes -- VCAM vascular cell adhesion molecule; Cardiovascular disease -- hypercholesterolemia -- endothelial dysfunction -- low-grade systemic inflammation -- atherosclerosis; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2021.106066
• Languages: English
• ISSNs: 1357-2725

Abstract

Highlights: PRIMARY hypercholesterolemia (PH) is associated with arteriosclerosis development. Low-grade systemic inflammation (LGSI) is involved in premature atherosclerosis. LGSI consists in elevated inflammatory mediators and platelet/leukocyte activation. TNFα induces endothelial dysfunction through different signaling pathways. Combined lipid-lowering/anti-TNFα therapies may impair cardiovascular disease in PH. Abstract: Primary hypercholesterolemia, a metabolic disorder characterized by elevated circulating levels of cholesterol products, mainly low-density lipoproteins, is associated with arteriosclerosis development. Cardiovascular disease, predominantly myocardial infarction and stroke, remains the main cause of death worldwide, with atherosclerosis considered to be the most common underlying pathology. In addition to elevated plasma levels of low-density lipoproteins, low-grade systemic inflammation and endothelial dysfunction seem to be the main drivers of premature atherosclerosis. Here we review current knowledge related to cellular and molecular mechanisms involved in low-grade systemic inflammation and endothelial dysfunction associated with primary hypercholesterolemia. We also discuss the contribution of different inflammatory mediators, immune players and signaling pathways implicated in leukocyte adhesion to the dysfunctional endothelium, a key feature of atherogenesis development. A better understanding of these processes linked to primary hypercholesterolemia should shed new light on cardiovascular disease development and might guide novel and effective therapeutic strategies to impair its progression.