Modified Lipoproteins Induce Arterial Wall Inflammation During Atherogenesis

Frontiers in Cardiovascular Medicine, Год журнала: 2022, Номер 9

Опубликована: Март 3, 2022

Circulating apolipoprotein B-containing lipoproteins, notably the low-density enter inner layer of arterial wall, intima, where a fraction them is retained and modified by proteases, lipases, oxidizing agents enzymes. The lipoproteins various modification products, such as fatty acids, ceramides, lysophospholipids, oxidized lipids induce inflammatory reactions in macrophages covering endothelial cells, initiating an increased leukocyte diapedesis. Lipolysis also induces formation cholesterol crystals with strong proinflammatory properties. Modified aggregated crystals, isolated from human atherosclerotic lesions, all can activate thereby secretion cytokines, chemokines, extent lipoprotein retention, modification, aggregation have been shown to depend largely on differences composition circulating particles. These properties be pharmacological means, provide opportunities for clinical interventions regarding prevention treatment vascular diseases.

Язык: Английский

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Oxidative Stress, Atherogenic Dyslipidemia, and Cardiovascular Risk

Biomedicines, Год журнала: 2023, Номер 11(11), С. 2897 - 2897

Опубликована: Окт. 26, 2023

Oxidative stress is the consequence of an overproduction reactive oxygen species (ROS) that exceeds antioxidant defense mechanisms. Increased levels ROS contribute to development cardiovascular disorders through oxidative damage macromolecules, particularly by oxidation plasma lipoproteins. One most prominent features atherogenic dyslipidemia accumulation small dense LDL (sdLDL) particles, characterized increased susceptibility oxidation. Indeed, a considerable and diverse body evidence from animal models epidemiological studies was generated supporting modification sdLDL particles as earliest event in atherogenesis. Lipid peroxidation results formation various bioactive atherosclerotic process different pathophysiological mechanisms, including foam cell formation, direct detrimental effects, receptor-mediated activation pro-inflammatory signaling pathways. In this paper, we will discuss recent data on role their interplay atherosclerosis. addition, special focus be placed clinical applicability novel, promising biomarkers these processes.

Язык: Английский

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The postprandial actions of GLP-1 receptor agonists: The missing link for cardiovascular and kidney protection in type 2 diabetes

Cell Metabolism, Год журнала: 2023, Номер 35(2), С. 253 - 273

Опубликована: Фев. 1, 2023

Язык: Английский

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Triglyceride-rich lipoproteins and cardiovascular diseases

Frontiers in Endocrinology, Год журнала: 2024, Номер 15

Опубликована: Май 31, 2024

The global prevalence of cardiovascular diseases (CVD) continues to rise steadily, making it a leading cause mortality worldwide. Atherosclerosis (AS) serves as primary driver these conditions, commencing silently at an early age and culminating in adverse events that severely impact patients’ quality life or lead fatality. Dyslipidemia, particularly elevated levels low-density lipoprotein cholesterol (LDL-C), plays pivotal role AS pathogenesis independent risk factor. Research indicates abnormal LDL-C accumulation within arterial walls acts crucial trigger for atherosclerotic plaque formation. As the disease progresses, may rupture dislodge, resulting thrombus formation complete blood supply obstruction, ultimately causing myocardial infarction, cerebral other common events. Despite adequate pharmacologic therapy targeting reduction, patients with cardiometabolic abnormalities remain high recurrence, highlighting importance addressing lipid factors beyond LDL-C. Recent attention has focused on causal relationship between triglycerides, triglyceride-rich lipoproteins (TRLs), their remnants risk. Genetic, epidemiologic, clinical studies suggest TRLs increased AS, this dyslipidemia be factor Particularly obesity, metabolic syndrome, diabetes, chronic kidney disease, disordered its significantly increase atherosclerosis development. Accumulation over-synthesized plasma, impaired function enzymes involved lipolysis, hepatic clearance cholesterol-rich can deposition remnants, promoting foam cell wall inflammation. Therefore, understanding TRLs-induced therapeutically could slow impede progression, thereby reducing morbidity mortality, coronary heart disease.

Язык: Английский

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A single, high-fat meal adversely affects postprandial endothelial function: a systematic review and meta-analysis

American Journal of Clinical Nutrition, Год журнала: 2022, Номер 116(3), С. 699 - 729

Опубликована: Июнь 6, 2022

Endothelial dysfunction is a predictive risk factor for the development of atherosclerosis and assessed by flow-mediated dilation (FMD). Although it known that NO-dependent endothelial occurs after consuming high-fat meal, magnitude effect factors affect response are unquantified.

Язык: Английский

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Hypolipidemic effects of macadamia oil are related to AMPK activation and oxidative stress relief: In vitro and in vivo studies

Food Research International, Год журнала: 2023, Номер 168, С. 112772 - 112772

Опубликована: Март 25, 2023

Язык: Английский

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Surf4 (Surfeit Locus Protein 4) Deficiency Reduces Intestinal Lipid Absorption and Secretion and Decreases Metabolism in Mice

Arteriosclerosis Thrombosis and Vascular Biology, Год журнала: 2023, Номер 43(4), С. 562 - 580

Опубликована: Фев. 9, 2023

Postprandial dyslipidemia is a causative risk factor for cardiovascular disease. The majority of absorbed dietary lipids are packaged into chylomicron and then delivered to circulation. Previous studies showed that Surf4 (surfeit locus protein 4) mediates very low-density lipoprotein secretion from hepatocytes. Silencing hepatic markedly reduces the development atherosclerosis in different mouse models without causing steatosis. However, role unknown.We developed inducible intestinal-specific knockdown mice (Surf4IKO) using Vil1Cre-ERT2 Surf4flox mice. Metabolic cages were used monitor metabolism. Enzymatic kits employed measure serum tissue lipid levels. expression target genes was detected by qRT-PCR Western Blot. Transmission electron microscopy radiolabeled oleic acid assess structure enterocytes intestinal absorption secretion, respectively. Proteomics performed determine changes jejunum.Surf4IKO mice, especially male Surf4IKO displayed significant body weight loss, increased mortality, reduced exhibited accumulation impaired fat secretion. Lipid droplets small vacuoles accumulated cytosol endoplasmic reticulum lumen colocalized with apoB co-immunoprecipitated apoB48 differentiated Caco-2 cells. Intestinal deficiency also significantly triglyceride, cholesterol, free fatty levels data revealed diverse pathways altered In addition, had mild liver damage, decreased size weight, triglyceride levels.Our findings demonstrate plays an essential suggest therapeutic use inhibition requires highly cell/tissue-specific targeting.

Язык: Английский

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The critical issue linking lipids and inflammation: Clinical utility of stopping oxidative stress

Frontiers in Cardiovascular Medicine, Год журнала: 2022, Номер 9

Опубликована: Ноя. 9, 2022

The formation of an atheroma begins when lipoproteins become trapped in the intima. Entrapped oxidized and activate innate immune system. This immunity represents primary association between lipids inflammation. When trapping continues, link inflammation becomes chronic detrimental, resulting atherosclerosis. entrapment ceases, is temporary healthy, atherogenic process halts. Therefore, depends upon lipoprotein retention due to electrostatic forces uniting apolipoprotein B polysaccharide chains on intimal proteoglycans. genetic transformation contractile smooth muscle cells media into migratory secretory produces protein, platelet-derived growth factor produced by activated platelets, stimulus for this change. Oxidative stress main platelets. minimizing oxidative would significantly reduce lipoproteins. Less decreases More importantly, it halt atherogenesis. review will analyze as critical lipids, inflammation, pathogenesis Through perspective, we discuss stopping disrupt a harmful Numerous therapeutic options be discussed mitigate stress. paper add new meaning Morse code distress signal SOS-stopping

Язык: Английский

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Molecular mechanisms underlying some major common risk factors of stroke

Heliyon, Год журнала: 2022, Номер 8(8), С. e10218 - e10218

Опубликована: Авг. 1, 2022

Ischemic and hemorrhagic strokes are the most common known cerebrovascular disease which can be induced by modifiable non-modifiable risk factors. Age race factors of stroke. However, hypertension, diabetes, obesity, dyslipidemia, physical inactivity, cardiovascular disorders major Understanding molecular mechanism mediating each these is expected to contribute significantly reducing stroke, preventing neural damage, enhancing rehabilitation, designing suitable treatments. Abnormalities in structure blood-brain barrier blood vessels, thrombosis, vasoconstriction, atherosclerosis, reduced cerebral flow, oxidative stress, inflammation, apoptosis, impaired synaptic transmission, excitotoxicity, altered expression/activities many channels signaling proteins knows mechanisms responsible for stroke induction. role not well understood requires a lot search reading. This review was designed provide reader with single source information that discusses current update prevalence, pathophysiology, all possible underlying some namely, diabetes mellitus, lipid fraction, inactivity. provides full resource understanding effect

Язык: Английский

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Postprandial Metabolic and Oxidative Stress Responses to Grape Pomace Extract in Healthy Normal and Overweight/Obese Women: A Randomized, Double-Blind, Placebo-Controlled Crossover Study

Nutrients, Год журнала: 2022, Номер 15(1), С. 156 - 156

Опубликована: Дек. 29, 2022

Postprandial oxidative stress has been shown to promote atherosclerosis. Grape pomace (GP) is a source of similar-to-wine bioactive micro-constituents with known antioxidant properties. The aim the present study was evaluate metabolic and responses after intake grape extract along high-fat meal, in normal overweight healthy women. In randomized, double-blind, placebo-controlled crossover study, 18 women were finally included, 11 BMI < 25 kg/m2 7 > kg/m2, consumed meal placebo or GP capsules two separate visits. Blood samples collected before 6 h consumption. Measurements included basic biochemical markers, uric acid (UA), protein carbonyls (PC), thiobarbituric substance (TBARS) levels, as well superoxide dismutase (SOD) glutathione peroxidase (GPx) activities. At certain time points, consumption normal-weight reduced UA, TBARS SOD activity, whereas it increased UA PC levels overweight/obese women, compared placebo. GP-derived compounds may exert actions during postprandial state through different mechanisms according their status.

Язык: Английский

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