The Effects of Type 2 Diabetes on Lipoprotein Composition and Arterial Stiffness in Male Youth

Gordon, Scott M.; Davidson, W. Sean; Urbina, Elaine M.; Dolan, Lawrence M.; Heink, Anna; Zang, Huaiyu; Lu, Long; Shah, Amy S.

doi:10.2337/db12-1753

Cited by 64 publications

(72 citation statements)

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“…In fact, the magnitude of the increase of HDL bound A1AT in this study was much greater than changes found in previous studies that examined the effect of various diseases or therapy on lipoprotein proteome (5,15,16). Additionally, A1AT has been shown to be involved in cardiovascular disease by modulating various inflammatory processes (17,18).…”

Section: Figcontrasting

confidence: 50%

“…The HDL peak was divided into two halves, representing large and small HDL, to gain additional insight given the proteomic complexity of HDL. Spectral counting was used as a semi-quantitative screen to identify proteins whose abundance changed because of rosuvastatin treatment, an experimental approach that has been validated in previous studies (9,15). As additional validation of the spectral counting approach, we also determined the correlation between spectral counts for apolipoprotein B and LDL-p.…”

Section: Effect Of Rosuvastatin On Lipoprotein Lipid Composition and mentioning

confidence: 99%

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Rosuvastatin Alters the Proteome of High Density Lipoproteins: Generation of alpha-1-antitrypsin Enriched Particles with Anti-inflammatory Properties*

Gordon

McKenzie

Kemeh

et al. 2015

Molecular & Cellular Proteomics

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Statins lower plasma cholesterol by as much as 50%, thus reducing future cardiovascular events. However, the physiological effects of statins are diverse and not all are related to low density lipoprotein cholesterol (LDL-C) lowering. We performed a small clinical pilot study to assess the impact of statins on lipoprotein-associated proteins in healthy individuals (n = 10) with normal LDL-C (<130 mg/ dL), who were treated with rosuvastatin (20 mg/day) for 28 days. Proteomic analysis of size-exclusion chromatography isolated LDL, large high density lipoprotein (HDL-L), and small HDL (HDL-S) fractions and spectral counting was used to compare relative protein detection before and after statin therapy. Significant protein changes were found in each lipoprotein pool and included both increases and decreases in several proteins involved in lipoprotein metabolism, complement regulation and acute phase response. The most dramatic effect of the rosuvastatin treatment was an increase in α-1-antirypsin (A1AT) spectral counts associated with HDL-L particles. Quantitative measurement by ELISA confirmed an average 5.7-fold increase in HDL-L associated A1AT. Molecular modeling predictions indicated that the hydrophobic reactive center loop of A1AT, the functional domain responsible for its protease inhibitor activity, is likely involved in lipid binding and association with HDL was found to protect A1AT against oxidative inactivation. Cell culture experiments, using J774 macrophages, demonstrated that the association of A1AT with HDL enhances its antiprotease activity, preventing elastase induced production of tumor necrosis factor α. In conclusion, we show that statins can significantly alter the protein composition of both LDL and HDL and our studies reveal a novel functional relationship between A1AT and HDL. The up-regulation of A1AT on

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Section: Figcontrasting

confidence: 50%

Section: Effect Of Rosuvastatin On Lipoprotein Lipid Composition and mentioning

confidence: 99%

Rosuvastatin Alters the Proteome of High Density Lipoproteins: Generation of alpha-1-antitrypsin Enriched Particles with Anti-inflammatory Properties*

Gordon

McKenzie

Kemeh

et al. 2015

Molecular & Cellular Proteomics

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“…All this parameters are known to be risk factors for cardiovascular diseases. We didn't found any significant improvement for plasma HDL cholesterol which is best recognized for its ability to shuttle excess cholesterol from peripheral tissues to the liver for excretion in the process of reverse cholesterol transport, likely contributing to the wellknown inverse relationship between HDL-cholesterol and cardiovascular diseases [6]. Plasma level of glucose, in our study, didn't change significantly but it was in normal range.…”

Section: Discussionmentioning

confidence: 45%

Effects of Nutritional Intervention on Vitamins and Minerals Intake at Overweight and Obese Patients

Posea¹,

Dragomir²,

Rusu³

et al. 2015

European Journal of Medicine. Series B

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Background and Aims-To evaluate the impact of nutritional intervention on vitamins and minerals from intake food and anthropometric parameters at overweight and obese patients.Material and methods-To a sample of 40 overweight and obese patients we evaluated the nutritional content of food intake (kilocalories, macro and micronutrients). We also measured anthropometric parameters like weight, body mass index, body fat, percent of body fat, abdominal circumference and arterial tension.Results-After the nutritional intervention, overweight and obese patients had significantly lower level of intake carbohydrates (P=.018), lipids (P=.002), B1 vitamin (P<.001), B3 vitamin (P=.02) and E vitamin (P=.016). There is a significantly increased level of proteins (P<.001). Regarding the minerals, we found that the intake levels of following‗s decreased: sodium (P<.001), magnesium (P=.006), zinc (P=.035), copper (P=.002), manganese (P<.001). Phosphorus is the only mineral of which the intake level increased significantly (P<.001). All the anthropometric parameters decreased significantly: weight (P<.001), body mass index (P<.001), body fat (P<.001), percent of body fat (P<.001), abdominal circumference (P<0.001), systolic arterial tension (P<.001), diastolic arterial tension (P=.002).Conclusions-All the patients had imbalanced intake of vitamins and minerals both before and after intervention. There is a significant improved on anthropometric measures after nutritional intervention. We need to promote healthy lifestyle changes to prevent the risks associated with obesity.Keywords: overweight; obese; intake food; vitamins; minerals; anthropometric measures. . Obesity is a major risk factor for type 2 diabetes, cardiovascular diseases (mainly stroke and heart disease), cancer (endometrial, breast, colon), pulmonary diseases, osteoporosis, periodontal diseases. It has numerous consequences on lipid, glucose and protein metabolism with hiperglicemia and insulin resistance, hiperlipidemia and hiperuricemia. Obesity apears as a consequence of imbalance between energy intake (by food) and consumed energy (mainly by phisical activities). Sedentary life and unhealthy meals, riched in energy-dense foods ( high-fat, high sugar, high-salt, micronutrient poor ) are the main problem of the contemporany world.Except the vitamin D, that is synthesized in the human body, in the cutaneous tissue, in response to sunlight exposure [2], all the other vitamins are provided by food intake. There are two types of vitamins-one's that are soluble in fat, like vitamins A, D, E. and K and other's that are soluble in water-like vitamins B1, B2, B3, B5, B6, B12, folic acid. Excess of fat-soluble vitamins can not be eliminated so this vitamins will be stored in human body if the intake level is high and it can lead to simptoms and diseases. The water soluble vitamins are eliminated through kidney or liver and the risk of intoxication is lower and the simptoms occurs rarely.Minerals represent only 4-5 % of body weight but they are very important by p...

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“…(27) As well as varying in size, HDL particles vary in protein content, as HDL's proteome is very rich. Alterations in protein cargo have been associated with pathological states, such as inflammation (28), poor response to therapy (29), autoimmune disease (30), and diabetes (31). Further improvements in quantitative techniques (32,33) and their application to clinical studies should identify panels of protein biomarkers that may be pharmacologically modifiable to reduce risk.…”

Section: Hdl-c Hypothesismentioning

confidence: 99%

The High Density Lipoprotein Cholesterol Hypothesis Revisited

2018

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IntroductionClassical epidemiology has established the incremental contribution of the high-density lipoprotein cholesterol (HDL-C) measure in the assessment of atherosclerotic cardiovascular disease (CVD) risk, yet, genetic epidemiology does not support a causal relationship between HDL-C and the future risk of myocardial infarction. Therapeutic interventions directed toward cholesterol loading of the HDL particle have been based on epidemiological studies that have established HDL cholesterol as a biomarker of atherosclerotic CVD risk. The reference range of HDL-C is 40-50 mg/dL in men and 50-60 mg/dL in women. However, therapeutic interventions such as niacin, cholesterylester transfer protein (CETP) inhibitors increase HDL-C in patients treated with statins, but have repeatedly failed to reduce CVD events.(1) Clinical trials with pharmacological therapies that increase the cholesterol content of HDL particles have failed to establish this convenient metric as The High Density Lipoprotein Cholesterol Hypothesis Revisited R E V I E W A R T I C L E B ACKGROUND:The strong inverse association of plasma levels of high-density lipoprotein cholesterol (HDL-C) with coronary heart disease (CHD) found in human epidemiological studies led to the development of the 'HDL-C hypothesis', which posits that intervention to raise HDL-C will result in reduced risk of CHD. However, recent evidence has raised doubts about the hypotheses that elevating HDL-C is necessarily therapeutic. Genetic variations that associate with altered HDL-C do not strongly associate with altered cardiovascular disease risk.CONTeNT: HDL-mediated cholesterol efflux from macrophage foam cells or measurements of the flux of cholesterol from macrophages to the liver and feces seem to correlate better with atherosclerotic burden than with HDL-C levels. Thus, it may be time to modify the HDL-C hypothesis to the 'HDL flux hypothesis', where intervention to promote cholesterol efflux and reverse cholesterol transport will reduce CHD risk, regardless of whether it affects plasma HDL-C levels. A deeper understanding of the complex biology of HDL metabolism and its relationship to reverse cholesterol transport and atherothrombotic events is urgently needed. This might lead to biomarkers of HDL flux and functionality that are more informative than simple measurements of HDL-C levels. SUmmARy:It is now clear from recent clinical trial and genetic studies that some approaches to raising HDL-C levels may have no effect on CHD. This suggests the need to evaluate HDL-C-raising therapies in different clinical populations, as well as therapies targeted toward HDL flux and function rather than simply HDL-C elevation. Perhaps moving from a focus on the HDL-C hypothesis to a focus on the HDL flux hypothesis will permit a biologically based reassessment of the optimal therapeutic approach to targeting HDL for reduction in cardiovascular risk.KeywORDS: reverse cholesterol transport, cholesterol efflux capacity, HDL dysfunction, HDL particle size, HDL lipidomics, HD...

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The Effects of Type 2 Diabetes on Lipoprotein Composition and Arterial Stiffness in Male Youth

Cited by 64 publications

References 40 publications

Rosuvastatin Alters the Proteome of High Density Lipoproteins: Generation of alpha-1-antitrypsin Enriched Particles with Anti-inflammatory Properties*

Rosuvastatin Alters the Proteome of High Density Lipoproteins: Generation of alpha-1-antitrypsin Enriched Particles with Anti-inflammatory Properties*

Effects of Nutritional Intervention on Vitamins and Minerals Intake at Overweight and Obese Patients

The High Density Lipoprotein Cholesterol Hypothesis Revisited

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