High-Density Lipoprotein

High-density lipoproteins (HDLs) protect against atherosclerosis by removing excess cholesterol from macrophages through the ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) pathways involved in reverse cholesterol transport. Factors that impair the availability of functional apolipoproteins or the activities of ABCA1 and ABCG1 could, therefore, strongly influence atherogenesis. HDL also inhibits lipid oxidation, restores endothelial function, exerts anti-inflammatory and antiapoptotic actions, and exerts anti-inflammatory actions in animal models. Such properties could contribute considerably to the capacity of HDL to inhibit atherosclerosis. Systemic and vascular inflammation has been proposed to convert HDL to a dysfunctional form that has impaired antiatherogenic effects. A loss of anti-inflammatory and antioxidative proteins, perhaps in combination with a gain of proinflammatory proteins, might be another important component in rendering HDL dysfunctional. The proinflammatory enzyme myeloperoxidase induces both oxidative modification and nitrosylation of specific residues on plasma and arterial apolipoprotein A-I to render HDL dysfunctional, which results in impaired ABCA1 macrophage transport, the activation of inflammatory pathways, and an increased risk of coronary artery disease. Understanding the features of dysfunctional HDL or apolipoprotein A-I in clinical practice might lead to new diagnostic and therapeutic approaches to atherosclerosis.

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“…Therapies that have been shown to improve or restore the functionality of some components of dysfunctional HDL include statins and niacin 105 .…”

Section: Improving Hdl Functionalitymentioning

confidence: 99%

Dysfunctional HDL and atherosclerotic cardiovascular disease

et al. 2015

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“…On the other hand, the pathophysiological role of the proposed targets may simply be not be fully understood: e.g., dalcetrapib did significantly increase HDL levels, however, this did not result in a significant reduction of adverse cardiovascular events (Schwartz et al, 2012). Thus, HDL levels alone do not seem to be a useful surrogate marker for prediction of adverse events and one rather needs to test HDL functionality to really make use of it as a therapeutic target (Luscher et al, 2014). Finally, a one-target strategy may simply be insufficient to successfully treat a disease as complex as CAD as there are redundant pathways.…”

Section: Why Have So Many Studies Failed?mentioning

confidence: 99%

Inflammatory therapeutic targets in coronary atherosclerosisâ€”from molecular biology to clinical application

et al. 2014

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Atherosclerosis is the leading cause of death worldwide. Over the past two decades, it has been clearly recognized that atherosclerosis is an inflammatory disease of the arterial wall. Accumulating data from animal experiments have supported this hypothesis, however, clinical applications making use of this knowledge remain scarce. In spite of optimal interventional and medical therapy, the risk for recurrent myocardial infarction remains by about 20% over 3 years after acute coronary syndromes, novel therapies to prevent atherogenesis or treat atherosclerosis are urgently needed. This review summarizes selected potential molecular inflammatory targets that may be of clinical relevance. We also review recent and ongoing clinical trails that target inflammatory processes aiming at preventing adverse cardiovascular events. Overall, it seems surprising that translation of basic science into clinical practice has not been a great success. In conclusion, we propose to focus on specific efforts that promote translational science in order to improve outcome and prognosis of patients suffering from atherosclerosis.

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“…In the early stage of dyslipidemia, endothelium becomes dysfunction in accompany with systemic inflammation and oxidation [3, 4]. Therefore, effectively treating dyslipidemia at an early stage by lifestyle modification or medicines should be beneficial for restoring endothelial function and preventing atherosclerosis progression [2].…”

Section: Introductionmentioning

confidence: 99%

Effects of rosuvastatin combined with fasudil therapy on rabbits with dyslipidemia

Lee

Qin

et al. 2015

Lipids Health Dis

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BackgroundPresent study was conducted to investigate the effects of rosuvastatin combined with fasudil on rabbits with dyslipidemia.MethodsDyslipidemia model of rabbits were produced by prescribing atherogenic diet for 2 weeks. Thereafter, 40 rabbits with dyslipidemia were randomly and evenly divided into four groups as follow: untreated group (orally prescribed 3 ml of normal saline), rosuvastatin group (orally prescribed 3 mg/kg body weight daily, dissolved in 3 ml of normal saline), fasudil group (intravenously prescribed 0.5 mg/kg body weight daily, dissolved in 3 ml of normal saline), and combined group (the same doses of rosuvastatin and fasudil as aforementioned). At baseline, 2 weeks of dyslipidemia establishment and 2 weeks of medical therapy, fasting venous blood was drawn for laboratory examination.ResultsAfter 2 weeks’ atherogenic diet treatment, lipid disorders and impaired fasting glucose were observed. Systemic inflammation and oxidation were also promoted as revealed by increased serum levels of high sensitive C-reactive protein (Hs-CRP) and malondialdehyde (MDA). Notably, endothelial function has been impaired significantly as reflected by decreased nitric oxide (NO) production and increased serum asymmetric dimethylarginine (ADMA) level. RhoA associated kinase (ROCK) activity was also profoundly enhanced (P < 0.05). Inter-group comparisons showed that when compared to untreated group, modest improvements of endothelial function, inflammation and oxidation were observed in rosuvastatin and fasudil groups (P > 0.05). These benefits were improved more prominently in combined group (P < 0.05). Intra-group comparisons also showed that when compared to 2 weeks of dyslipidemia, slight improvement of endothelial function, inflammation and oxidation in rosuvastatin and fasudil groups were observed (P > 0.05). The improvements were more prominent in the combined groups (P < 0.05).ConclusionRosuvastatin combined with fasudil conferred synergistic effects on endothelium-protection and inflammation- and oxidation-amelioration in the setting of early stage of dyslipidemia.

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High-Density Lipoprotein

Abstract: This Review is part of a thematic series on High-Density Lipoprotein, which includes the following articles:

Cited by 234 publications

References 124 publications

Dysfunctional HDL and atherosclerotic cardiovascular disease

Dysfunctional HDL and atherosclerotic cardiovascular disease

Inflammatory therapeutic targets in coronary atherosclerosisâ€”from molecular biology to clinical application

Effects of rosuvastatin combined with fasudil therapy on rabbits with dyslipidemia

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