High-Density Lipoprotein as a Therapeutic Target

Singh, Inder; Shishehbor, Mehdi H.; Ansell, Benjamin J.

doi:10.1001/jama.298.7.786

Cited by 436 publications

(295 citation statements)

References 114 publications

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“…Liver is an important organ for the cholesterol metabolism where HDL-C brings cholesterol from the peripheral tissues to the liver thereby cholesterol gets metabolized into bile acids (Singh et al 2007). Indeed, this pathway plays a vital role in reducing cholesterol levels in the blood and peripheral tissues (Garvey et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Myrtenal alleviates hyperglycaemia, hyperlipidaemia and improves pancreatic insulin level in STZ-induced diabetic rats

Ayyasamy

Pari

2016

Pharmaceutical Biology

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Context: Myrtenal is monoterpene a constituent of essential oils found mainly in herbs such as mint, pepper, cumin, etc. It exerts admirable pharmacological activities against many diseases including diabetes. Hyperlipidaemia is a secondary complication of diabetes and also a major risk factor for cardiovascular diseases.Objective: The present study investigated the possible antihyperlipidaemic efficacy of myrtenal on plasma glucose, pancreatic insulin, plasma and tissue lipid levels in streptozotocin (STZ) induced diabetic rats. Materials and methods: Diabetes was induced in male Wistar rats by a single intraperitoneal injection of STZ (40 mg/kg b.w.). Myrtenal (80 mg/kg) was administered orally to diabetic rats for a period of 28 d. Plasma glucose, pancreatic insulin, TC, TGs, FFAs, PLs, LDL-C, HDL-C, VLDL, atherogenic index, (HMG-CoA) reductase, LPL, LCAT and liver histology were analyzed. Results: Diabetic rats showed significantly (p < 0.05) increased plasma glucose (273.18 mg/dL), total cholesterol (142 mg/dL), triglycerides (126 mg/dL), free fatty acids (118 mg/dL), phospholipids (153 mg/dL), lowdensity lipoprotein (88.07 mg/dL), very low-density lipoprotein (25.2 mg/dL), atherogenic index, whereas a decrease in the levels of pancreatic insulin (97.48 ng/mg) and high-density lipoprotein (29.12 mg/dL). In addition, the activity of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase (0.94 HMG-CoA ratio/(mevalonate) increased significantly in contrast to the activities of lipoprotein lipase (4.87 lmoles of glycerol liberated/h/L) and lecithin cholesterol acyltransferase (54.61 lmoles of cholesterol esterified/h/L) in diabetic rats. Treatment with myrtenal significantly (p < 0.05) improved the levels of plasma glucose, pancreatic insulin and lipid profiles. Moreover, the histopathological analysis of liver was also in agreement with the biochemical findings. Discussion and conclusions: The present study indicates that myrtenal possess antihyperglycaemic and antihyperlipidemic properties, and could potentially be a useful phytochemical in treating diabetes. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Myrtenal alleviates hyperglycaemia, hyperlipidaemia and improves pancreatic insulin level in STZ-induced diabetic rats

Ayyasamy

Pari

2016

Pharmaceutical Biology

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“…In vivo, we chose a gene transfer strategy, because currently available drugs, such as fibrates, nicotinacids, and statins, only moderately and not exclusively increase HDL. 23 The STZ-induced diabetes mellitus model is characterized by severe HG and is, in contrast to other diabetic animal models, not associated with reduced HDL levels. 24,25 Apo A-I gene transfer did not affect glucose or LDL cholesterol levels, 2 factors known to influence AT1R expression and reduced aortic AT1R mRNA in STZ-induced diabetic rats to levels similar to nondiabetic controls.…”

Section: Discussionmentioning

confidence: 99%

Vascular-Protective Effects of High-Density Lipoprotein Include the Downregulation of the Angiotensin II Type 1 Receptor

et al. 2009

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Abstract-There is growing evidence that a cross-talk exists between the renin-angiotensin (Ang) system and lipoproteins.We investigated the role of high-density lipoprotein (HDL) on Ang II type 1 receptor (AT1R) regulation and subsequent Ang II-mediated signaling under diabetic conditions. To investigate the effect of HDL on AT1R expression in vivo, apolipoprotein A-I gene transfer was performed 5 days after streptozotocin injection. Six weeks after apolipoprotein A-I gene transfer, the 1.9-fold (Pϭ0.001) increase of HDL cholesterol was associated with a 4.7-fold (PϽ0.05) reduction in diabetes mellitus-induced aortic AT1R expression. Concomitantly, NAD(P)H oxidase activity, Nox 4, and p22 phox mRNA expression were reduced 2.6-fold, 2.0-fold, and 1.5-fold (PϽ0.05), respectively, whereas endothelial NO synthase dimerization was increased 3.3-fold (PϽ0.005). Apolipoprotein A-I transfer improved NO bioavailability as indicated by ameliorated acetylcholine-dependent vasodilation in the streptozotocin-Ad.hapoA-I group compared with streptozotocin-induced diabetes mellitus. In vitro, HDL reduced the hyperglycemia-induced upregulation of the AT1R in human aortic endothelial cells. This was associated with a 1.3-fold and 2.2-fold decreases in reactive oxygen species and NAD(P)H oxidase activity, respectively (PϽ0.05). Finally, HDL reduced the responsiveness to Ang II, as indicated by decreased oxidative stress in the hyperglycemiaϩHDLϩAng II group compared with the hyperglycemiaϩAng II group. In conclusion, vascular-protective effects of HDL include the downregulation of the AT1R. Diabetes mellitus is associated with endothelial dysfunction, an early phase of atherosclerosis further characterized by a reduction in NO bioavailability, without significant morphological changes of the vessel wall. 1,2 Both diabetes mellitus-associated hyperglycemia and increased angiotensin (Ang) II levels 3 induce reactive oxygen species (ROS), which contribute to endothelial dysfunction, partly via oxidative degradation of NO. Recent studies have demonstrated that ROS are predominantly produced by vascular NAD(P)H oxidase (NOX), 4 whereas "uncoupled" endothelial NO synthase (eNOS; when eNOS produces O 2 ⅐Ϫ rather then NO) is another important source of ROS in diseased, including diabetic, blood vessels. 5 Numerous studies have shown that activation of the Ang II type 1 receptor (AT1R) contributes to the induction of oxidative stress and apoptosis of vascular cells, thus contributing to the initiation and progression of endothelial dysfunction. 6 Ang II not only increases NOX activity but also uncouples eNOS in diabetic mice. 7 The expression levels of the AT1R define the biological efficacy of Ang II and have been shown to be regulated by several agonists, such as Ang II, glucose, insulin, ROS, low-density lipoprotein (LDL), and many others, 8,9 including diabetes mellitus. 10,11 The importance of the enhanced vascular AT1R expression and Ang II-mediated signaling in diabetes mellitus-associated endothelial dysfunction follows from the ...

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“…Risk factors can include diabetes mellitus, smoking tobacco, age, family history, hypertension, male sex and hyperlipidemia. Among those with lipid abnormalities, increased low density lipoprotein cholesterol (LDL-C) and reduced highdensity lipoprotein cholesterol (HDL-C) concentrations have been associated with heart disease [3][4][5][6][7]. Conversely, higher HDL-C levels have been correlated with fewer cardiac events including those with low LDL-C [8].…”

Section: Introductionmentioning

confidence: 99%

“…Novel forms of therapy which increase HDL-C have been studied but are not available to the general public [7,[11][12][13]. Non-pharmacologic treatments including life style changes such as smoking cessation, weight loss, physical activity and alcohol consumption can increase HDL-C from 12% to 21% [7,14,15].…”

Section: Introductionmentioning

confidence: 99%

Prospective randomized clinical trial evaluating the impact of vinegar on lipids in non-diabetics

Panetta¹,

Jonk²,

Shapiro³

2013

WJCD

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Background: Heart disease is now considered an inflammatory process targeted primarily by medical therapy on lipid levels. Complementary and alternative medicine searches for novel non-pharmacologic therapy, including pursuing various diets. Animal studies and consumer literature suggest benefits of vinegar on lipid levels and diabetes mellitus. Our nonrandomized pilot study from our group suggested a benefit in raising high-density lipoprotein cholesterol (HDL-C). Based on this data, we conducted a randomized placebo controlled clinical trial to determine the effects of apple cider vinegar intake in those without diabetes mellitus on total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides, HDL-C, Hemoglobin A1C (Hgb-A1C) and measurement of inflammation with high sensitivity CRP levels (HS-CRP). Methods: A prospective randomized, double blind, placebo-controlled clinical trial consisting of 114 participants was conducted. Participants consumed 30 mL of either apple cider vinegar or placebo for two months. Measurements were collected at baseline, eight and sixteen weeks.

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High-Density Lipoprotein as a Therapeutic Target

Cited by 436 publications

References 114 publications

Myrtenal alleviates hyperglycaemia, hyperlipidaemia and improves pancreatic insulin level in STZ-induced diabetic rats

Myrtenal alleviates hyperglycaemia, hyperlipidaemia and improves pancreatic insulin level in STZ-induced diabetic rats

Vascular-Protective Effects of High-Density Lipoprotein Include the Downregulation of the Angiotensin II Type 1 Receptor

Prospective randomized clinical trial evaluating the impact of vinegar on lipids in non-diabetics

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