An octimibate derivative, Oxa17, enhances cholesterol efflux and exerts anti-inflammatory and atheroprotective effects in experimental atherosclerosis

2021 ◽  
Vol 188 ◽  
pp. 114581
Author(s):  
Pi-Fen Tsui ◽  
Ching-Yuh Chern ◽  
Chih-Feng Lien ◽  
Feng-Yen Lin ◽  
Chien-Sung Tsai ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Experimental Atherosclerosis ◽  
Anti Inflammatory

Anti-inflammatory drugs in experimental atherosclerosis

1989 ◽  
Vol 76 (2-3) ◽  
pp. 155-161 ◽  
Author(s):  
A.N. Makheja ◽  
S. Bloom ◽  
R. Muesing ◽  
T. Simon ◽  
J.M. Bailey
Keyword(s):  
Experimental Atherosclerosis ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

scholarly journals Carvedilol Ameliorates Experimental Atherosclerosis by Regulating Cholesterol Efflux and Exosome Functions

2019 ◽  
Vol 20 (20) ◽  
pp. 5202 ◽  
Author(s):  
Chen ◽  
Tsui ◽  
Chuang ◽  
Chiang ◽  
Chen ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Nuclear Factor Κb ◽  
Experimental Atherosclerosis ◽  
Atherosclerotic Cardiovascular Disease ◽  
Beneficial Effects ◽  
Abca1 Expression ◽  
Density Lipoprotein Receptor ◽  
And Function

Carvedilol (Cav), a nonselective β-blocker with α1 adrenoceptor blocking effect, has been used as a standard therapy for coronary artery disease. This study investigated the effects of Cav on exosome expression and function, ATP-binding cassette transporter A1 (ABCA1) expression, and cholesterol efflux that are relevant to the process of atherosclerosis. Human monocytic (THP-1) cell line and human hepatic (Huh-7) cells were treated with Cav, and cholesterol efflux was measured. Exosomes from cell culture medium or mice serum were isolated using glycan-coated recognition beads. Low-density lipoprotein receptor knockout (ldlr−/−) mice were fed with high-fat diet and treated with Cav. Cav accentuated cholesterol efflux and enhanced the expressions of ABCA1 protein and mRNA in both THP-1 and Huh-7 cells. In addition, Cav increased expression and function of exosomal ABCA1 in THP-1 macrophage exosomes. The mechanisms were associated with inhibition of nuclear factor-κB (NF-κB) and protein kinase B (Akt). In hypercholesterolemic ldlr−/− mice, Cav enhanced serum exosomal ABCA1 expression and suppressed atherosclerosis by inhibiting lipid deposition and macrophage accumulation. Cav halts atherosclerosis by enhancing cholesterol efflux and increasing ABCA1 expression in macrophages and in exosomes, possibly through NF-κB and Akt signaling, which provides mechanistic insights regarding the beneficial effects of Cav on atherosclerotic cardiovascular disease.

scholarly journals Multimodal Clinical Imaging To Longitudinally Assess a Nanomedical Anti-Inflammatory Treatment in Experimental Atherosclerosis

2010 ◽  
Vol 7 (6) ◽  
pp. 2020-2029 ◽  
Author(s):  
Mark E. Lobatto ◽  
Zahi A. Fayad ◽  
Stephane Silvera ◽  
Esad Vucic ◽  
Claudia Calcagno ◽  
...  
Keyword(s):  
Experimental Atherosclerosis ◽  
Clinical Imaging ◽  
Anti Inflammatory

1: COMPARATIVE EFFECT OF SELECTIVE AND NON-SELECTIVE COX-2 INHIBITORS ON LIPID ACCUMULATION IN HUMAN MACROPHAGES

2016 ◽  
Vol 64 (3) ◽  
pp. 800.1-800
Author(s):  
LJ Kasselman ◽  
I Voloshyna ◽  
MJ Littlefield ◽  
N Siegart ◽  
SE Carsons ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Receptor Expression ◽  
Scavenger Receptors ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Human Macrophages ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors ◽  
Efflux Proteins

Purpose of StudyIt is the second decade of controversy regarding the cardiovascular (CV) effects of cycloxygenase-2 (COX-2) inhibitors. COX-2 inhibitors possess anti-inflammatory and analgesic effects comparable with conventional non-steroidal anti-inflammatory drugs, but produce fewer gastrointestinal adverse effects. Here we demonstrate that only selective COX-2 inhibitors cause disruption of the delicate balance between cholesterol efflux and influx that leads to lipid overload and macrophage foam cell formation (FCF).Methods UsedTHP-1 human macrophages were incubated with: celecoxib (10 µM, 25 µM); rofecoxib (10 µM, 25 µM); naproxen (10 µM, 25 µM); acetaminophen (0.5 mM, 1 mM)±oxidized low density lipoprotein (oxLDL, 25 µg/ml, 48 h) or 5 µg/ml (Dil)-oxLDL. FCF (% oil red O stained cells) and oxLDL accumulation were determined (fluorescent intensity). Scavenger receptors: CD36, LOX-1, SR-A1 and CXCL16 and cholesterol efflux proteins: ATP-binding cassette transporter (ABC) A1 and ABCG1 were detected in macrophages by QRT-PCR and immunocytochemistry.Summary of ResultsCelecoxib decreased ABCA1 and ABCG1 message in a concentration dependent manner: 68.2±13.36% for ABCA1 and 65.7±13.36% for ABCG1 (control set at 100%, n=6, P<0.01). Neither naproxen nor acetaminophen significantly affected expression of cholesterol efflux proteins. Both specific and nonspecific COX-2 inhibitors had a significant impact on expression of scavenger receptors CD36, LOX-1 and SR-A1–nearly double control (n=6, P<0.05). However, only specific COX-2 inhibitors significantly increased FCF in THP-1 differentiated macrophages (62.2±5.2% for celecoxib and 56.3±3.4% for rofecoxib vs. 33.5±5.1% for untreated cells, P<0.05).ConclusionsHere we report that only specific COX-2 inhibitors might contribute to atherogenesis by promoting lipid overload and lipoprotein accumulation. This may explain, in part, the increased CV risk in patients taking COX-2 inhibitors for extended periods. Despite increased scavenger receptor expression, naproxen and acetaminophen do not impact lipid content, perhaps because efflux pathways remain intact.

Influence of Anti-inflammatory Agents on Experimental Atherosclerosis

Nature ◽  
1966 ◽  
Vol 212 (5063) ◽  
pp. 731-732 ◽  
Author(s):  
J. MARTYN BAILEY ◽  
JEAN BUTLER
Keyword(s):  
Experimental Atherosclerosis ◽  
Anti Inflammatory

scholarly journals Reactive Dicarbonyl Scavenging Effectively Reduces MPO-Mediated Oxidation of HDL and Preserves HDL Atheroprotective Functions

2019 ◽  
Author(s):  
Jiansheng Huang ◽  
Patricia G. Yancey ◽  
Huan Tao ◽  
Mark Borja ◽  
Loren Smith ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Adduct Formation ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Dependent Manner ◽  
Cholesterol Efflux Capacity ◽  
Hdl Function ◽  
Impaired Ability ◽  
Anti Inflammatory ◽  
Mediated Oxidation

AbstractHigh-density lipoprotein (HDL) is atheroprotective by mediating cholesterol efflux, anti-inflammatory, and anti-oxidation functions. Atheroprotective functions of HDL are related to the activity of HDL-associated enzymes such as paraoxonase 1 (PON1). We examined the impact of inhibition of myeloperoxidase (MPO)-mediated HDL oxidation by PON1 on HDL malondialdehyde (MDA) content and HDL function. In the presence of PON1, crosslinking of apoAI in response to MPO-mediated oxidation of HDL was abolished and MDA-HDL adduct levels were decreased. In addition, PON1 prevented the impaired cholesterol efflux capacity of MPO-oxidized HDL from Apoe-/- macrophages. Direct modification of HDL with MDA increased apoAI crosslinking and reduced the cholesterol efflux capacity in a dose dependent manner. In addition, MDA modification of HDL reduced its anti-inflammatory function compared to native HDL as the expression of IL-1β and IL6 increased by 3-(p<0.05) and 1.8-fold (p<0.05) in Apoe-/- macrophages in response to LPS. MDA-HDL also had impaired ability to increase PON1 activity. Importantly, HDL from subjects with familial hypercholesterolemia (FH-HDL) versus controls had increased MDA-apoAI adducts, and normalization of the PON1 activity to PON1 mass revealed a 24 % (p<0.05) decrease in specific activity indicating that PON1 activity is also impaired in FH. Consistent with the impaired PON1 activity and increased MDA-apoAI, FH-HDL induced a pro-inflammatory response in Apoe-/- macrophages compared to incubation with LPS alone. FH-HDL versus control HDL also had an impaired ability to promote cholesterol efflux from Apoe-/- macrophages. Interestingly, reactive dicarbonyl scavengers effectively abolished MPO-mediated apoAI crosslinking, MDA adduct formation, and improved cholesterol efflux capacity. Importantly, in vivo treatment of hypercholesterolemic mice with reactive dicarbonyl scavengers effectively reduced MDA-HDL adduct formation and increased PON1 activity and HDL cholesterol efflux capacity, supporting a therapeutic potential of reactive carbonyl scavenging in maintaining HDL function.

scholarly journals Impaired High‐Density Lipoprotein Function in Patients With Heart Failure

2021 ◽  
Author(s):  
Johanna E. Emmens ◽  
Congzhuo Jia ◽  
Leong L. Ng ◽  
Dirk J. van Veldhuisen ◽  
Kenneth Dickstein ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Cholesterol Concentration ◽  
Hdl Function ◽  
Patients With Heart Failure ◽  
Hdl Functionality ◽  
Anti Inflammatory

Background We recently showed that, in patients with heart failure, lower high‐density lipoprotein (HDL) cholesterol concentration was a strong predictor of death or hospitalization for heart failure. In a follow‐up study, we suggested that this association could be partly explained by HDL proteome composition. However, whether the emerging concept of HDL function contributes to the prognosis of patients with heart failure has not been addressed. Methods and Results We measured 3 key protective HDL function metrics, namely, cholesterol efflux, antioxidative capacity, and anti‐inflammatory capacity, at baseline and after 9 months in 446 randomly selected patients with heart failure from BIOSTAT‐CHF (A Systems Biology Study to Tailored Treatment in Chronic Heart Failure). Additionally, the relationship between HDL functionality and HDL proteome composition was determined in 86 patients with heart failure. From baseline to 9 months, HDL cholesterol concentrations were unchanged, but HDL cholesterol efflux and anti‐inflammatory capacity declined (both P <0.001). In contrast, antioxidative capacity increased ( P <0.001). Higher HDL cholesterol efflux was associated with lower mortality after adjusting for BIOSTAT‐CHF risk models and log HDL cholesterol (hazard ratio, 0.81; 95% CI, 0.71–0.92; P =0.001). Other functionality measures were not associated with outcome. Several HDL proteins correlated with HDL functionality, mainly with cholesterol efflux. Apolipoprotein A1 emerged as the main protein associated with all 3 HDL functionality measures. Conclusions Better HDL cholesterol efflux at baseline was associated with lower mortality during follow‐up, independent of HDL cholesterol. HDL cholesterol efflux and anti‐inflammatory capacity declined during follow‐up in patients with heart failure. Measures of HDL function may provide clinical information in addition to HDL cholesterol concentration in patients with heart failure.

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