Atheroprotective Effects of High-Density Lipoproteins

Assmann, Gerd; Nofer, Jerzy–Roch

doi:10.1146/annurev.med.54.101601.152409

Cited by 314 publications

(244 citation statements)

References 80 publications

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“…This is because high level of HDL-C protects endothelial cells from the cytotoxic effects of oxidized LDL. 19 In the present study, a significant lowering of plasma TG level with simultaneous increase in plasma HDL-C definitely indicate the beneficial role of PIO administration to hyperlipidemic animals.…”

Section: Discussionsupporting

confidence: 69%

Hypolipidemic and antioxidant activities of pioglitazone in hyperlipidemic rats

Bhosale

Jadhav

Padwal

et al. 2013

Int J Basic Clin Pharmacol

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Background: Diabetes mellitus (DM) is an endocrine disorder characterized by abnormal carbohydrate, lipid and protein metabolism along with specific long-term complications which are associated with hyperlipidemia and oxidative stress. Hence, it is important to find hypoglycemic drug that improves lipid profile and reduces oxidative stress in diabetic patient. This study, therefore, was performed to investigate hypolipidemic and antioxidant potential of Pioglitazone (PIO) in hyperlipidemic rats. Methods: Hyperlipidemia was induced in normal rats by including 0.75 gm% cholesterol and 1.5 gm% bile salt in normal diet and these rats were used for the experiments. PIO hydrochloride was administered as 10 mg/kg and 30 mg/kg dose levels to the hyperlipidemic rats. Hypolipidemic activity was estimated by plasma lipid profile parameters while antioxidant potential was estimated by ascorbic acid, catalase activity, malondialdehyde and superoxide dismutase activity using standard methods. Statistical analysis was done by one way analysis of variance (ANOVA) followed by Dunnett’s test. Results: Treatment with 10 mg/kg and 30 mg/kg dose levels of PIO hydrochloride resulted in a significant decrease in serum TG and VLDL only in 30 mg/kg PIO treated group and significant increase in serum HDL in both groups, but no significant decrease in cholesterol and LDL in both PIO treated groups. PIO increased activities of catalase enzyme and concentration of malondialdehyde significantly in only 30 mg/kg PIO treated group. But there were no significant changes in the superoxide dismutase activity and ascorbic acid concentration in both PIO treated groups. Conclusions: The present study demonstrated that treatment with 10 mg/kg and 30 mg/kg dose levels of PIO hydrochloride improves the plasma lipid profile and also reduces oxidative stress in hyperlipidemic animals. [Int J Basic Clin Pharmacol 2013; 2(1.000): 77-82

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Section: Discussionsupporting

confidence: 69%

Hypolipidemic and antioxidant activities of pioglitazone in hyperlipidemic rats

Bhosale

Jadhav

Padwal

et al. 2013

Int J Basic Clin Pharmacol

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“…16 Contrary to LDLs, high-density lipoproteins (HDLs) exhibit antiatherogenic and cardioprotective properties. 17 Besides their classical function in the reverse cholesterol transport, HDLs possess anti-inflammatory and antioxidant properties. 18 HDLs inhibit LDLs oxidation, and counteract several adverse biological effects, such as cytotoxicity and inflammatory response triggered by cytokines, oxLDLs or oxidants.…”

mentioning

confidence: 99%

HDLs inhibit endoplasmic reticulum stress and autophagic response induced by oxidized LDLs

et al. 2010

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The apoptotic effect of oxidized LDLs (oxLDLs) is mediated through a complex sequence of signaling events involving a deregulation of the cytosolic Ca 2 þ homeostasis. OxLDLs also trigger ER stress that may lead to cellular dysfunction and apoptosis, through the activation of the IRE1a/c-Jun N-terminal kinase pathway. Moreover, ER stress and oxidized lipids have been shown to trigger autophagy. The antiatherogenic high-density lipoproteins (HDLs) display protective effects against oxLDLs toxicity. To more deeply investigate the mechanisms mediating the protective effects of HDLs, we examined whether ER stress and autophagy were implicated in oxLDLs-induced apoptosis and whether HDLs prevented these stress processes. We report that, in human endothelial cells, HDLs prevent the oxLDL-induced activation of the ER stress sensors IRE1a, eIF2a and ATF6 and subsequent activation of the proapoptotic mediators JNK and CHOP. OxLDLs also trigger the activation of autophagy, as assessed by LC3 processing and Beclin-1 expression. The autophagic process is independent of the proapoptotic arms of ER stress, but Beclin-1 contributes to PS exposure and subsequent phagocytosis of oxLDLs exposed cells. Induction of autophagy and PS exposure by oxLDLs is prevented by HDLs. Finally, the cytosolic Ca 2 þ deregulation triggered by oxLDLs is a common signaling pathway that mediates ER stress-induced cell death and autophagy, all these events being blocked by HDLs.

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“…Cholesterol efflux, in which excess cellular cholesterol is released from cells and transferred to HDL particles, is the first step of reverse cholesterol transport. HDL seems to stimulate cholesterol efflux by two distinct mechanisms (3,4). One mechanism involves unspecific passive diffusion of cholesterol to the HDL particle.…”

mentioning

confidence: 99%

Involvement of Cdc42 Signaling in ApoA-I-induced Cholesterol Efflux

Nofer

Feuerborn

Levkau

et al. 2003

Journal of Biological Chemistry

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Cholesterol efflux, an important mechanism by which high density lipoproteins (HDL) protect against atherosclerosis, is initiated by docking of apolipoprotein A-I (apoA-I), a major HDL protein, to specific binding sites followed by activation of ATP-binding cassette transporter A1 (ABCA1) and translocation of cholesterol from intracellular compartments to the exofacial monolayer of the plasma membrane where it is accessible to HDL. In this report, we investigated potential signal transduction pathways that may link apoA-I binding to cholesterol translocation to the plasma membrane and cholesterol efflux. By using pull-down assays we found that apoA-I substantially increased the amount of activated Cdc42, Rac1, and Rho in human fibroblasts. Moreover, apoA-I induced actin polymerization, which is known to be controlled by Rho family G proteins. Inhibition of Cdc42 and Rac1 with Clostridium difficile toxin B inhibited apoA-I-induced cholesterol efflux, whereas inhibition of Rho with Clostridium botulinum C3-exoenzyme exerted opposite effects. Adenoviral expression of a Cdc42(T17N) dominant negative mutant substantially reduced apoA-I-induced cholesterol efflux, whereas dominant negative Rac1(T17N) had no effect. We further found that two downstream effectors of Cdc42/Rac1 signaling, c-Jun N-terminal kinase (JNK) and p38 mitogenactivated protein kinase (p38 MAPK), are activated by apoA-I. Pharmacological inhibition of JNK but not p38 MAPK decreased apoA-I-induced cholesterol efflux, whereas anisomycin and hydrogen peroxide, two direct JNK activators, could partially substitute for apoA-I in its ability to induce cholesterol efflux. These results for the first time demonstrate activation of Rho family G proteins and stress kinases by apoA-I and implicate the involvement of Cdc42 and JNK in the apoA-I-induced cholesterol efflux.

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Atheroprotective Effects of High-Density Lipoproteins

Cited by 314 publications

References 80 publications

Hypolipidemic and antioxidant activities of pioglitazone in hyperlipidemic rats

Hypolipidemic and antioxidant activities of pioglitazone in hyperlipidemic rats

HDLs inhibit endoplasmic reticulum stress and autophagic response induced by oxidized LDLs

Involvement of Cdc42 Signaling in ApoA-I-induced Cholesterol Efflux

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