Importance of blood cellular genomic profile in coronary heart disease

Baba, M. Iqbal; Kaul, Deepak; Grover, Anil

doi:10.1007/s11373-005-9041-y

Cited by 12 publications

(6 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We evaluated effects of plant stanol ester consumption on PPARa mRNA expression in isolated PBMC. It has been shown that mRNA expression of PPARa and especially LXRa in these cells is related to serum cholesterol concentrations and CHD risk (16). However, we did not find any change in the expression of both transcription factors in PBMC.…”

Section: Discussioncontrasting

confidence: 94%

A Plant Stanol Yogurt Drink Alone or Combined with a Low-Dose Statin Lowers Serum Triacylglycerol and Non-HDL Cholesterol in Metabolic Syndrome Patients

Plat

Brufau

Dallinga‐Thie³

et al. 2009

The Journal of Nutrition

View full text Add to dashboard Cite

We evaluated the effects of 2 commonly available strategies (plant stanol ester drink and 10 mg simvastatin) on coronary heart disease (CHD) risk variables in participants with metabolic syndrome. Metabolic syndrome patients are at increased risk to develop CHD, partly due to high triacylglycerol (TAG) and low HDL cholesterol (HDL-C) concentrations and a low-grade inflammatory profile. Effects of plant stanol esters on TAG concentrations in these participants are unknown. After a 3-wk run-in period in which individuals consumed placebo yogurt drinks and placebo capsules, participants were randomly divided into 4 groups: placebo (n = 9), simvastatin + placebo drink (n = 10), placebo + stanol drink (n = 9), and simvastatin + stanol drink (n = 8). After 9 wk, we evaluated the effects on serum lipids, low-grade inflammation, and endothelial dysfunction markers. In metabolic syndrome patients, stanol esters (2.0 g/d), simvastatin, or the combination lowered non-HDL-C by 12.8% (P = 0.011), 30.7% (P < 0.001), and 35.4% (P < 0.001), respectively, compared with placebo. TAG were lowered by 27.5% (P = 0.044), 21.7% (P = 0.034), and 32.7% (P < 0.01), respectively. The total-:HDL-C ratio was significantly lowered in all 3 intervention groups. We found no treatment effects on the apolipoprotein CII:CIII ratio, cholesterol ester transfer protein mass, FFA concentrations, and markers for low-grade inflammation or endothelial dysfunction. This study shows that in metabolic syndrome patients, plant stanol esters lower not only non-HDL-C, but also TAG. Effects on TAG were also present in combination with statin treatment, illustrating an additional benefit of stanol esters in this CHD risk population.

show abstract

Section: Discussioncontrasting

confidence: 94%

A Plant Stanol Yogurt Drink Alone or Combined with a Low-Dose Statin Lowers Serum Triacylglycerol and Non-HDL Cholesterol in Metabolic Syndrome Patients

Plat

Brufau

Dallinga‐Thie³

et al. 2009

The Journal of Nutrition

View full text Add to dashboard Cite

show abstract

“…LXR-α has been widely recognized as a master gene that plays a crucial role in cholesterol homeostasis, lipid peroxidation and inflammation responsible for the initiation of CHD and its clinical implications [1][2][3][4][5][6][7] . Apart from the observed protective effects of LXR-α agonists in the various cellular and animal model systems [8][9][10][11][12][13][14] , the importance of LXR-α in pathogenesis of CHD is further highlighted by the studies from our laboratory which showed that both statins (drug of choice for CHD) and vitamin C have an inherent capacity to upregulate LXR-α expression [15] and also that human CHD subjects (with or without hyperlipidemia) have conspicuously higher blood cellular LXR-α mRNA expression as compared to their normal healthy counterparts [16] . However, synthetic agonists for the LXR-α activation designed as therapeutic agents for the regression of coronary atherosclerosis did not meet the expected success.…”

Section: Discussionmentioning

confidence: 99%

“…The observation that statins as well as vitamin C, both have an inherent ability to upregulate LXR-α [15] further underline its importance. Findings from our laboratory have demonstrated that both normolipidemic and hyperlipidemic human coronary heart disease (CHD) subjects have significantly higher expression of blood cellular LXR-α as compared to the corresponding controls [16] . This is in sharp contrast with the observed protective role of LXR-α.…”

Section: Introductionmentioning

confidence: 99%

Blood cellular mutant LXR-α protein stability governs initiation of coronary heart disease

Arora

Kaul²,

Sharma³

2013

WJC

View full text Add to dashboard Cite

AIM:To investigate the role of [breast and ovarian cancer susceptibility 1 (BRCA1)-associated RING domain 1 (BARD1)]/BRCA1 E3-ubiquitin ligase complex in governing the stability of mutant liver X receptor-α (LXR-α) protein in coronary heart disease (CHD) subjects. METHODS:The expression analysis of various genes was carried out by quantitative real time polymerase chain reaction and western blotting within blood mononuclear cells of human CHD subjects at various stages of coronary occlusion and their corresponding normal healthy counterparts. Immunoprecipitation experiments were performed to establish protein interactions between LXR-α and BARD1. Peripheral blood mononuclear cells were cultured and exposed to Vitamin D3 and Cisplatin to validate the degradation of mutant LXR-α protein in CHD subjects by BARD1/BRCA1 complex. RESULTS:The expression of mutant LXR-α protein in CHD subjects was found to decrease gradually with the severity of coronary occlusion exhibiting a strong nega- culture experiments proved that Vitamin D3 could prevent the degradation of mutant LXR-α and restore its functional activity to some extent. BRIEF ARTICLE World Journal of CONCLUSION:Mutant LXR-α protein in CHD subjects is degraded by BARD1/BRCA1 complex and Vitamin D3 can rescue and restore its function.

show abstract

“…Each experiment was performed in duplicate. The means of the duplicates were used for subsequent calculations [19].…”

Section: Homocysteine Estimation Homocysteine Estimation Was Per-mentioning

confidence: 99%

Effects of Nitric Oxide Modulators on Cardiovascular Risk Factors in Mild Hyperhomocysteinaemic Rat Model

Sharma

Kr.

et al. 2008

Basic Clin Pharma Tox

View full text Add to dashboard Cite

Hyperhomocysteinaemia is considered to be an independent risk factor in atherosclerosis. In the present article, we observed the effect of nitric oxide modulators on cardiovascular risk factors in mild hyperhomocysteinaemic rats. A rat model of mild hyperhomocysteinaemia was established by administering methionine (1 g/kg body weight, orally) for 4 weeks. The other groups were concomitantly treated with sodium nitroprusside (SNP) and N ω -nitro-l -arginine (LNNA) during the induction of hyperhomocysteinaemia. Lipid profile, total antioxidant capacity and the level of homocysteine and NO x (nitrates and nitrites) was examined in serum at 0 and 4 weeks. Activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the mRNA level of caveolin, P2 receptors and cardiovascular risk factors were also analysed. Stimulated lipid profile of rats by the treatment of methionine (1 g/kg body weight) reduced significantly by the treatment of SNP with methionine. LNNA increased the level of cholesterol in aorta (P < 0.05 versus group II). SNP significantly suppressed the activity of HMG-CoA reductase. The mRNA levels of caveolin (P < 0.05), P2X (P < 0.05) and P2Y (P < 0.05) showed a significant decrease in rats administered with SNP. LNNA showed significant induction in the expression of caveolin (P < 0.01) and P2Y (P < 0.01) expression. The level of P2X showed no remarkable change in animals treated with LNNA and methionine both. These data conclude that nitric oxide modulators modulate the effect of hyperhomocysteinaemia on the other cardiovascular risk factors and confirm the finding that nitric oxide plays an important role in homocysteine-induced cardiovascular diseases.Hyperhomocysteinaemia is a significant risk factor in cardiovascular diseases like atherosclerosis. Extensive clinical research has been performed showing a more tenuous relationship between homocysteine-lowering treatment and cardiovascular end-points than the research community expected. The causality of hyperhomocysteinaemia in the context of atherosclerosis has therefore been doubted. One of the observed mechanism by which hyperhomocysteinaemia initiated its effect is endothelial dysfunction [1,2]. The most important and well-known endothelium-derived mediator that is responsible for endothelium dysfunction is nitric oxide [3]. Nitric oxide release by the endothelium regulates blood flow, inflammation and platelet aggregation, and consequently its disruption during endothelial dysfunction can decrease plaque stability and encourage the formation of atherosclerotic lesions and thrombi [4].There is some controversy as to the effects of hyperhomocysteinaemia on nitric oxide production: it has been shown that hyperhomocysteinaemia both up-regulates [5] and downregulates it [6]. From our previous in vivo studies on the effect of different doses of methionine in rats, we observed that nitric oxide level decreases in a dose-dependent manner [7]. The studies by Zhang et al . also showed that high homocysteine level in serum suppresses the ni...

show abstract

Importance of blood cellular genomic profile in coronary heart disease

Cited by 12 publications

References 29 publications

A Plant Stanol Yogurt Drink Alone or Combined with a Low-Dose Statin Lowers Serum Triacylglycerol and Non-HDL Cholesterol in Metabolic Syndrome Patients

A Plant Stanol Yogurt Drink Alone or Combined with a Low-Dose Statin Lowers Serum Triacylglycerol and Non-HDL Cholesterol in Metabolic Syndrome Patients

Blood cellular mutant LXR-α protein stability governs initiation of coronary heart disease

Effects of Nitric Oxide Modulators on Cardiovascular Risk Factors in Mild Hyperhomocysteinaemic Rat Model

Contact Info

Product

Resources

About