scholarly journals HMG CoA reductase inhibitors lower LDL cholesterol without reducing Lp(a) levels.

Circulation ◽  
1989 ◽  
Vol 80 (5) ◽  
pp. 1313-1319 ◽  
Author(s):  
G M Kostner ◽  
D Gavish ◽  
B Leopold ◽  
K Bolzano ◽  
M S Weintraub ◽  
...  
Keyword(s):  
Ldl Cholesterol ◽  
Hmg Coa Reductase ◽  
Reductase Inhibitors ◽  
Hmg Coa Reductase Inhibitors ◽  
Coa Reductase

P-Glycoprotein Is Downregulated in KG1a Primitive Leukaemia Cells by LDL Cholesterol Deprivation and by HMG-CoA Reductase Inhibitors.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4192-4192
Author(s):  
Laura Connelly-Smith ◽  
Joanne Pattinson ◽  
Martin Grundy ◽  
Shili Shang ◽  
Claire Seedhouse ◽  
...  
Keyword(s):  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hmg Coa Reductase ◽  
Serum Free ◽  
Reductase Inhibitors ◽  
P Glycoprotein ◽  
Hmg Coa Reductase Inhibitors ◽  
Coa Reductase ◽  
And Function

Abstract P-glycoprotein (pgp) is a membrane transporter encoded by the multidrug resistance (MDR1, ABCB1) gene. Pgp is a poor prognostic factor in elderly patients with acute myeloid leukaemia (AML). In addition to its role in drug efflux, pgp has been implicated in cellular cholesterol homeostasis. We investigated the effects of exogenous cholesterol removal on pgp expression and function. KG1a drug-naïve, primitive leukaemia cells were cultured in serum free medium with or without the addition of low density lipoprotein (LDL) cholesterol. After 72 hours pgp expression and function was assessed by flow cytometry and total cholesterol content of the KG1a cells was determined by the Amplex Red® cholesterol assay. The addition of clinically available cholesterol lowering agents, HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors to KG1a cells was also assessed. There was a 39% (SEM 8.3% P=0.03) decrease in pgp protein expression after 3 days of serum free culture without HMG-CoA reductase inhibitors. Message was decreased by 40% (P=0.01) and pgp function was also reduced by 40% (P=0.005). The addition of low density lipoprotein (LDL) cholesterol restored pgp expression to 86% of the basal value. The addition of a HMG-CoA reductase inhibitor to KG1a cells in serum free culture resulted in a further 26% (lovastatin, P=0.03) and 16% (pravastatin, P=0.05) reduction in pgp respectively. Lovastatin also significantly reduced cellular cholesterol levels by 47% (P=0.002) under serum free conditions. Furthermore, the toxicity of the pgp substrate drug daunorubicin was significantly enhanced following lovastatin pre-culture (P=0.04). We conclude that LDL/cholesterol contributes to pgp expression and chemoresistance in primitive leukaemia cells. The use of HMG-CoA reductase inhibitors may be of clinical value in lowering pgp expression in AML.

P-glycoprotein is downregulated in KG1a-primitive leukemia cells by LDL cholesterol deprivation and by HMG-CoA reductase inhibitors

2007 ◽  
Vol 35 (12) ◽  
pp. 1793-1800 ◽  
Author(s):  
Laura Connelly-Smith ◽  
Joanne Pattinson ◽  
Martin Grundy ◽  
Shili Shang ◽  
Claire Seedhouse ◽  
...  
Keyword(s):  
Ldl Cholesterol ◽  
Leukemia Cells ◽  
Hmg Coa Reductase ◽  
Reductase Inhibitors ◽  
P Glycoprotein ◽  
Hmg Coa Reductase Inhibitors ◽  
Coa Reductase

Statins and Inflammation in Cardiovascular Disease

2018 ◽  
Vol 23 (46) ◽  
pp. 7027-7039 ◽  
Author(s):  
Georgia Vogiatzi ◽  
Evangelos Oikonomou ◽  
Gerasimos Siasos ◽  
Sotiris Tsalamandris ◽  
Alexandros Briasoulis ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Lipid Lowering ◽  
Hmg Coa Reductase ◽  
Ample Evidence ◽  
Reductase Inhibitors ◽  
Immune System Activation ◽  
Hmg Coa Reductase Inhibitors ◽  
Anti Inflammatory ◽  
Artery Disease ◽  
Coa Reductase

Background: Chronic inflammation and immune system activation underlie a variety of seemingly unrelated cardiac conditions including not only atherosclerosis and the subsequent coronary artery disease but also peripheral artery disease, hypertension with target organ damage and heart failure. The beneficial effects of HMG-CoA reductase inhibitors or statins are mainly attributed to their ability to inhibit hepatic cholesterol biosynthesis. Beyond their lipid lowering activity, ample evidence exists in support of their potent anti-inflammatory properties which initiate from the inhibition of GTPase isoprenylation, activating a cataract of secondary pathways and extend to the inhibition and blocking of immune cell activation and interaction. </P><P> Objective: To summarize the anti-inflammatory mechanisms of statins in clinical and experimental settings in cardiovascular disease. </P><P> Methods: A systematic search of PubMed and the Cochrane Database was conducted in order to identify the majority of trials, studies, current guidelines and novel articles related to the subject. </P><P> Results: In vitro, statins have immuno-modulatory and anti-inflammatory effects, and they can exert antiatherosclerotic effects independently of their hypolipidemic actions. In addition, positive results have emerged from mechanistic and experimental studies on the active role of HMG-CoA reductase inhibitors in HF. By extrapolating those data in clinical setting, we further understand how HMG-CoA reductase inhibitors can beneficially affect not only systolic but also diastolic HF. </P><P> Conclusion: In this review article, we present the basic pathophysiologic data supporting the anti-inflammatory actions of statins in clinical and experimental settings and we link these mechanisms with confirmatory clinical data on the potent non lipid lowering effects of HMG-CoA reductase inhibitors.

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