Mahdi Garelnabi - Academia.edu (original) (raw)
Papers by Mahdi Garelnabi
Medical science monitor : international medical journal of experimental and clinical research, 2015
Background Paraoxonase-1 (PON1) enzyme is reported in various types of tissues and linked to nume... more Background Paraoxonase-1 (PON1) enzyme is reported in various types of tissues and linked to numerous pathophysiological disorders. It is a potential biomarker in many pathological conditions such as cardiovascular diseases. Material and Methods We conducted several small-scale studies to evaluate PON1 performance as affected by sample types, storage, and interferences. We also carried out short-term studies to compare the performance of the widely used PON1 assay to the similar commercially available PON1 kit assay method; sample size for the method comparison was N=40, and the number varied for other validation experiments. Results Our studies using various types of anticoagulants show that samples collected in tubes with NaF, citrate, EDTA, clot activator, and sodium heparin have increased PON1 levels that are 49%, 24.5%, 19.8%, 11.4%, and 8%, respectively, higher compared to serum samples collected in plain tubes. However, samples collected in lithium heparin tubes demonstrated ...
North American journal of medical sciences, 2010
Azelaic acid (AzA) is the best known dicarboxilic acid to have pharmaceutical benefits and clinic... more Azelaic acid (AzA) is the best known dicarboxilic acid to have pharmaceutical benefits and clinical applications and also to be associated with some diseases pathophysiology. We extracted and methylesterified AzA and determined its concentration in human plasma obtained from healthy individuals and also in mice fed AzA containing diet for three months. AzA was detected in Gas Chromatography (GC) and confirmed by Liquid chromatography mass spectrometry (LCMS), and gas chromatography mass spectrometry (GCMC). Our results have shown that AzA can be determined efficiently in selected biological samples by GC method with 1nM limit of detection (LoD) and the limit of quantification (LoQ); was established at 50nM. Analytical Sensitivity as assayed by hexane demonstrated an analytical sensitivity at 0.050nM. The method has demonstrated 8-10% CV batch repeatability across the sample types and 13-18.9% CV for the Within-Lab Precision analysis. The method has shown that AzA can efficiently be ...
Journal of assisted reproduction and genetics, 2014
To investigate the serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), mon... more To investigate the serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and Paraoxonase-1 (PON-1) during fertility treatment of women with endometriosis (Endo), PCOS or unexplained infertility (Unexpl). Thirty-six patients with Endo, PCOS or Unexpl undergoing controlled ovarian stimulation for IVF or IUI were consented and their serum, on day-3 (baseline) and at the end of FSH treatment (peak), was collected and investigated for levels of TNF-α, IL-6, MCP-1, and PON-1. Correlations, ANOVA and Student's t-test were used for statistical analysis. Peak serum levels of IL-6, MCP-1 and PON-1 were positively correlated to E2 peak levels. TNF-α levels were inversely correlated to estradiol levels and they were lower in patients who ultimately became pregnant when compared to non-pregnant (P < 0.05). Mean TNF-α levels were significantly higher in Unexpl group (P < 0.05). The mean levels of IL-6, and MCP-1 were significa...
Journal of the International Society of Sports Nutrition, 2014
We proposed that mice supplemented with quercetin, a class of flavonoids known to have antioxidan... more We proposed that mice supplemented with quercetin, a class of flavonoids known to have antioxidant and anti-inflammatory properties, will have profound effects on the pathophysiology of atherosclerosis when combined with exercise. Forty C57BL6 LDLr -/- mice were divided into four groups (n = 10): control untreated (NN); control group supplemented with 100 μg/day of quercetin (NQ); exercise group (EN); and exercise group supplemented with 100 μg/day of quercetin (EQ). All animals were fed atherogenic diet. The exercise groups were run on a treadmill for 30 minutes, 15 m/min for 5 days/week for 30 days. After 30 day animals were sacrificed and tissues were harvested. Mice supplemented with quercetin during exercise sessions had 78% atherosclerotic plaque reduction compared to control mice and 40% less atherosclerotic plaque formation compared to control group supplemented with quercetin. The manifestation of the combination of quercetin supplementation with exercise was more evident i...
Novel Strategies in Ischemic Heart Disease, 2012
Nutrition, Metabolism and Cardiovascular Diseases, 2012
Cardiovascular disease; Atherosclerosis * Corresponding author. Tel.: þ1 614 292 5572; fax: þ1 61... more Cardiovascular disease; Atherosclerosis * Corresponding author. Tel.: þ1 614 292 5572; fax: þ1 614 292 9259. a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / n m c d Nutrition, Metabolism & Cardiovascular Diseases (2012) 22, 907e913 0939-4753/$ -see front matter ª
The Journal of Lipid Research, 2008
Low-dose aspirin therapy has become a standard in the treatment of cardiovascular diseases. Aspir... more Low-dose aspirin therapy has become a standard in the treatment of cardiovascular diseases. Aspirin has been shown to inhibit atherosclerosis in mouse models. To determine the mechanisms by which aspirin might inhibit atherosclerosis, we incubated HEPG2 cells and rat primary hepatocytes with aspirin or salicylic acid and noted an increase in paraoxonase 1(PON1) activity in the medium, together with an induction of PON1 and apolipoprotein A-I (apoA-I) gene expression. Mice treated with aspirin also showed a 2-fold increase in plasma PON1 activity and a significant induction of both PON1 and apoA-
Journal of Clinical Laboratory Analysis, 2010
Physical activity or exercise is a proven deterrent of cardiovascular (CV) diseases. In this stud... more Physical activity or exercise is a proven deterrent of cardiovascular (CV) diseases. In this study, we examined the relationships between baseline values of parameters related to physical activity and known markers of CV disease, including markers of oxidative stress. A total of 455 healthy men and women between the ages of 18 and 50 were recruited to participate in the study. Levels of lipids/lipoproteins and markers of oxidative stress and inflammation were measured along with the VO(2) and duration time spent on treadmill. Women, in general, had a significantly (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) higher plasma high density lipoprotein (1.51+/-0.30 mmol/l), decreased (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) low density lipoprotein (LDL) (2.75+/-0.66 mmol/l), and decreased (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) triglycerides levels (2.09+/-0.85 mmol/l), compared with males (1.21+/-0.23 mmol/l, 2.92+/-0.81 mmol/l, and 3.02+/-1.34 mmol/l, respectively). There was a direct correlation between the levels of plasma LDL and the levels oxidized LDL levels (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) in both men and women. Despite a better antiatherogenic lipid profile, the levels of C-reactive protein in women were significantly (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) elevated (3.78+/-3.66 ng/ml) as compared with those in men (1.82+/-2.37 ng/ml). These results suggest intrinsic sex differences between men and women in relation to atherogenic risk.
Fertility and Sterility, 2011
Fertility and Sterility, 2013
Clinical Biochemistry, 2013
Apolipoprotein A5 (ApoA5) is a key regulator of plasma triglycerides (TG), even though its plasma... more Apolipoprotein A5 (ApoA5) is a key regulator of plasma triglycerides (TG), even though its plasma concentration is very low compared to other known apoproteins. Over the years, researchers have attempted to elucidate the molecular mechanisms by which ApoA5 regulates plasma TG in vivo. Though still under debate, two theories broadly describe how ApoA5 modulates TG levels: (i) ApoA5 enhances the catabolism of TG-rich lipoproteins and (ii) it inhibits the rate of production of very low-density lipoprotein (VLDL), the major carrier of TGs. This review will summarize the basic and clinical studies that describe the importance of ApoA5 in TG metabolism. Population studies conducted in various countries have demonstrated an association between single nucleotide polymorphisms (SNPs) in ApoA5 and the increased risk to cardiovascular disease and metabolic syndrome (including diabetes and obesity). ApoA5 is also highly expressed during liver regeneration and is an acute phase protein associated with HDL, which is independent of its effects on TG metabolism. Conclusion: Despite considerable evidences available from clinical and basic research studies on the role of ApoA5 in TG metabolism and its indirect link to metabolic diseases, additional investigations are needed to understand the paradoxical role of this important apoprotein is modulated by both diet and its polymorphism variants.
Clinical Biochemistry, 2008
Background: Free oxygen radicals play an important role in the pathogenesis of many diseases incl... more Background: Free oxygen radicals play an important role in the pathogenesis of many diseases including cardiovascular disease, diabetes, hypertension, cancer and aging. Several methods were developed for the direct or indirect measurement of oxygen free radical and its byproducts. The free oxygen radicals monitor (FORM) is a novel point-of-care system for the rapid measurement of free oxygen radicals (FORT) in blood. We have carefully evaluated the use of this assay for batch analysis of plasma samples in a research environment with respect to factors affecting its performance, including storage temperature and duration.
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2008
The low density lipoprotein (LDL) oxidation hypothesis has generated considerable interest in oxi... more The low density lipoprotein (LDL) oxidation hypothesis has generated considerable interest in oxidative stress and how it might affect atherosclerosis. However, the failure of antioxidants, particularly vitamin E, to affect the progression of the disease in humans has convinced even staunch supporters of the hypothesis to take a step backwards and reconsider alternatives.
Biochimica et Biophysica Acta (BBA) - General Subjects, 2005
Livers of C57 BL/6 mice exercised for 2 weeks showed a dramatic increase in scavenger receptor B1... more Livers of C57 BL/6 mice exercised for 2 weeks showed a dramatic increase in scavenger receptor B1 (SR-B1), CD36 and low density lipoprotein (LDL) receptor and a decrease in acetyl LDL receptor gene expression. These effects on lipoprotein receptors are reminiscent of the effects mediated by peroxisome proliferator-activated receptor (PPARgamma) ligands.
Atherosclerosis, 2008
Previously we have shown that intestinal cells efficiently take up oxidized fatty acids (OxFAs) a... more Previously we have shown that intestinal cells efficiently take up oxidized fatty acids (OxFAs) and that atherosclerosis is increased when animals are fed a high cholesterol diet in the presence of oxidized linoleic acid. Interestingly, we found that in the absence of dietary cholesterol, the oxidized fatty acid fed low-density lipoprotein (LDL) receptor negative mice appeared to have lower plasma triglyceride (TG) levels as compared to animals fed oleic acid. In the present study, we fed C57BL6 mice a normal mice diet supplemented with oleic acid or oxidized linoleic acid (at 18 mg/animal/ day) for 2 weeks. After the mice were sacrificed, we measured the plasma lipids and collected livers for the isolation of RNA. The results showed that while there were no significant changes in the levels of total cholesterol and high-density lipoprotein cholesterol (HDLc), there was a significant decrease (41.14%) in the levels of plasma TG in the mice that were fed oxidized fatty acids.
Atherosclerosis, 2010
Background-Atherosclerosis is a chronic inflammatory disease associated with the accumulation of ... more Background-Atherosclerosis is a chronic inflammatory disease associated with the accumulation of oxidized lipids in arterial lesions. Recently we studied the degradation of peroxidized linoleic acid and suggested that oxidation is an essential process that results in the generation of terminal products, namely mono-and dicarboxylic acids that may lack the pro-atherogenic effects of peroxidized lipids. In continuation of that study, we tested the effects of azelaic acid (AzA), one of the end products of linoleic acid peroxidation, on the development of atherosclerosis using low density lipoprotein receptor knockout (LDLr −/− ) mice.
Antioxidants & Redox Signaling, 2009
The decomposition of peroxidized lipids of low-density lipoprotein (LDL) has been suggested to be... more The decomposition of peroxidized lipids of low-density lipoprotein (LDL) has been suggested to be involved in atherosclerosis. In this study, an in vitro system with 13-hydroperoxylinoleic acid (13-HPODE) was used to determine the effects of antioxidants on its decomposition. Decomposition of 13-HPODE was not affected by a-tocopherol, several other antioxidants, or antioxidant enzymes. Moreover, the inclusion of a-tocopherol during the decomposition of 13-HPODE resulted in an accumulation of aldehydes. Further oxidation of aldehydes to carboxylic acids by a number of oxidases was prevented by a-tocopherol. Conversely, the formation of carboxylic acids may be conducive to plaque stabilization via immunomodulation, rapid degradation, and by calcium sequestration. Thus, the inhibition of formation of carboxylic acids could be a serious deleterious effect of antioxidant treatment. In contrast, a-keto acids, like pyruvic acid, promoted the conversion of 13-HPODE to 13-hydroxylinoleic acid (13-HODE) by readily undergoing decarboxylation into acetate. These observations suggest that agents that promote the reduction of lipid peroxides into lipid hydroxides could be far more effective in treating cardiovascular diseases as opposed a-tocopherol-like antioxidants that could affect additional steps in the oxidation cascade. Antioxid. Redox Signal. 11, 1237-1248.
The Journal of Heart and Lung Transplantation, 2008
Our results reflect differential roles of VEGF isoforms with regards to EC permeability, clarifyi... more Our results reflect differential roles of VEGF isoforms with regards to EC permeability, clarifying the factors associated with the development of native atherosclerosis and AV. Identification of novel therapeutic strategies by selectively targeting specific VEGF isoforms may be possible.
Medical science monitor : international medical journal of experimental and clinical research, 2015
Background Paraoxonase-1 (PON1) enzyme is reported in various types of tissues and linked to nume... more Background Paraoxonase-1 (PON1) enzyme is reported in various types of tissues and linked to numerous pathophysiological disorders. It is a potential biomarker in many pathological conditions such as cardiovascular diseases. Material and Methods We conducted several small-scale studies to evaluate PON1 performance as affected by sample types, storage, and interferences. We also carried out short-term studies to compare the performance of the widely used PON1 assay to the similar commercially available PON1 kit assay method; sample size for the method comparison was N=40, and the number varied for other validation experiments. Results Our studies using various types of anticoagulants show that samples collected in tubes with NaF, citrate, EDTA, clot activator, and sodium heparin have increased PON1 levels that are 49%, 24.5%, 19.8%, 11.4%, and 8%, respectively, higher compared to serum samples collected in plain tubes. However, samples collected in lithium heparin tubes demonstrated ...
North American journal of medical sciences, 2010
Azelaic acid (AzA) is the best known dicarboxilic acid to have pharmaceutical benefits and clinic... more Azelaic acid (AzA) is the best known dicarboxilic acid to have pharmaceutical benefits and clinical applications and also to be associated with some diseases pathophysiology. We extracted and methylesterified AzA and determined its concentration in human plasma obtained from healthy individuals and also in mice fed AzA containing diet for three months. AzA was detected in Gas Chromatography (GC) and confirmed by Liquid chromatography mass spectrometry (LCMS), and gas chromatography mass spectrometry (GCMC). Our results have shown that AzA can be determined efficiently in selected biological samples by GC method with 1nM limit of detection (LoD) and the limit of quantification (LoQ); was established at 50nM. Analytical Sensitivity as assayed by hexane demonstrated an analytical sensitivity at 0.050nM. The method has demonstrated 8-10% CV batch repeatability across the sample types and 13-18.9% CV for the Within-Lab Precision analysis. The method has shown that AzA can efficiently be ...
Journal of assisted reproduction and genetics, 2014
To investigate the serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), mon... more To investigate the serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and Paraoxonase-1 (PON-1) during fertility treatment of women with endometriosis (Endo), PCOS or unexplained infertility (Unexpl). Thirty-six patients with Endo, PCOS or Unexpl undergoing controlled ovarian stimulation for IVF or IUI were consented and their serum, on day-3 (baseline) and at the end of FSH treatment (peak), was collected and investigated for levels of TNF-α, IL-6, MCP-1, and PON-1. Correlations, ANOVA and Student's t-test were used for statistical analysis. Peak serum levels of IL-6, MCP-1 and PON-1 were positively correlated to E2 peak levels. TNF-α levels were inversely correlated to estradiol levels and they were lower in patients who ultimately became pregnant when compared to non-pregnant (P < 0.05). Mean TNF-α levels were significantly higher in Unexpl group (P < 0.05). The mean levels of IL-6, and MCP-1 were significa...
Journal of the International Society of Sports Nutrition, 2014
We proposed that mice supplemented with quercetin, a class of flavonoids known to have antioxidan... more We proposed that mice supplemented with quercetin, a class of flavonoids known to have antioxidant and anti-inflammatory properties, will have profound effects on the pathophysiology of atherosclerosis when combined with exercise. Forty C57BL6 LDLr -/- mice were divided into four groups (n = 10): control untreated (NN); control group supplemented with 100 μg/day of quercetin (NQ); exercise group (EN); and exercise group supplemented with 100 μg/day of quercetin (EQ). All animals were fed atherogenic diet. The exercise groups were run on a treadmill for 30 minutes, 15 m/min for 5 days/week for 30 days. After 30 day animals were sacrificed and tissues were harvested. Mice supplemented with quercetin during exercise sessions had 78% atherosclerotic plaque reduction compared to control mice and 40% less atherosclerotic plaque formation compared to control group supplemented with quercetin. The manifestation of the combination of quercetin supplementation with exercise was more evident i...
Novel Strategies in Ischemic Heart Disease, 2012
Nutrition, Metabolism and Cardiovascular Diseases, 2012
Cardiovascular disease; Atherosclerosis * Corresponding author. Tel.: þ1 614 292 5572; fax: þ1 61... more Cardiovascular disease; Atherosclerosis * Corresponding author. Tel.: þ1 614 292 5572; fax: þ1 614 292 9259. a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / n m c d Nutrition, Metabolism & Cardiovascular Diseases (2012) 22, 907e913 0939-4753/$ -see front matter ª
The Journal of Lipid Research, 2008
Low-dose aspirin therapy has become a standard in the treatment of cardiovascular diseases. Aspir... more Low-dose aspirin therapy has become a standard in the treatment of cardiovascular diseases. Aspirin has been shown to inhibit atherosclerosis in mouse models. To determine the mechanisms by which aspirin might inhibit atherosclerosis, we incubated HEPG2 cells and rat primary hepatocytes with aspirin or salicylic acid and noted an increase in paraoxonase 1(PON1) activity in the medium, together with an induction of PON1 and apolipoprotein A-I (apoA-I) gene expression. Mice treated with aspirin also showed a 2-fold increase in plasma PON1 activity and a significant induction of both PON1 and apoA-
Journal of Clinical Laboratory Analysis, 2010
Physical activity or exercise is a proven deterrent of cardiovascular (CV) diseases. In this stud... more Physical activity or exercise is a proven deterrent of cardiovascular (CV) diseases. In this study, we examined the relationships between baseline values of parameters related to physical activity and known markers of CV disease, including markers of oxidative stress. A total of 455 healthy men and women between the ages of 18 and 50 were recruited to participate in the study. Levels of lipids/lipoproteins and markers of oxidative stress and inflammation were measured along with the VO(2) and duration time spent on treadmill. Women, in general, had a significantly (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) higher plasma high density lipoprotein (1.51+/-0.30 mmol/l), decreased (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) low density lipoprotein (LDL) (2.75+/-0.66 mmol/l), and decreased (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) triglycerides levels (2.09+/-0.85 mmol/l), compared with males (1.21+/-0.23 mmol/l, 2.92+/-0.81 mmol/l, and 3.02+/-1.34 mmol/l, respectively). There was a direct correlation between the levels of plasma LDL and the levels oxidized LDL levels (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) in both men and women. Despite a better antiatherogenic lipid profile, the levels of C-reactive protein in women were significantly (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) elevated (3.78+/-3.66 ng/ml) as compared with those in men (1.82+/-2.37 ng/ml). These results suggest intrinsic sex differences between men and women in relation to atherogenic risk.
Fertility and Sterility, 2011
Fertility and Sterility, 2013
Clinical Biochemistry, 2013
Apolipoprotein A5 (ApoA5) is a key regulator of plasma triglycerides (TG), even though its plasma... more Apolipoprotein A5 (ApoA5) is a key regulator of plasma triglycerides (TG), even though its plasma concentration is very low compared to other known apoproteins. Over the years, researchers have attempted to elucidate the molecular mechanisms by which ApoA5 regulates plasma TG in vivo. Though still under debate, two theories broadly describe how ApoA5 modulates TG levels: (i) ApoA5 enhances the catabolism of TG-rich lipoproteins and (ii) it inhibits the rate of production of very low-density lipoprotein (VLDL), the major carrier of TGs. This review will summarize the basic and clinical studies that describe the importance of ApoA5 in TG metabolism. Population studies conducted in various countries have demonstrated an association between single nucleotide polymorphisms (SNPs) in ApoA5 and the increased risk to cardiovascular disease and metabolic syndrome (including diabetes and obesity). ApoA5 is also highly expressed during liver regeneration and is an acute phase protein associated with HDL, which is independent of its effects on TG metabolism. Conclusion: Despite considerable evidences available from clinical and basic research studies on the role of ApoA5 in TG metabolism and its indirect link to metabolic diseases, additional investigations are needed to understand the paradoxical role of this important apoprotein is modulated by both diet and its polymorphism variants.
Clinical Biochemistry, 2008
Background: Free oxygen radicals play an important role in the pathogenesis of many diseases incl... more Background: Free oxygen radicals play an important role in the pathogenesis of many diseases including cardiovascular disease, diabetes, hypertension, cancer and aging. Several methods were developed for the direct or indirect measurement of oxygen free radical and its byproducts. The free oxygen radicals monitor (FORM) is a novel point-of-care system for the rapid measurement of free oxygen radicals (FORT) in blood. We have carefully evaluated the use of this assay for batch analysis of plasma samples in a research environment with respect to factors affecting its performance, including storage temperature and duration.
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2008
The low density lipoprotein (LDL) oxidation hypothesis has generated considerable interest in oxi... more The low density lipoprotein (LDL) oxidation hypothesis has generated considerable interest in oxidative stress and how it might affect atherosclerosis. However, the failure of antioxidants, particularly vitamin E, to affect the progression of the disease in humans has convinced even staunch supporters of the hypothesis to take a step backwards and reconsider alternatives.
Biochimica et Biophysica Acta (BBA) - General Subjects, 2005
Livers of C57 BL/6 mice exercised for 2 weeks showed a dramatic increase in scavenger receptor B1... more Livers of C57 BL/6 mice exercised for 2 weeks showed a dramatic increase in scavenger receptor B1 (SR-B1), CD36 and low density lipoprotein (LDL) receptor and a decrease in acetyl LDL receptor gene expression. These effects on lipoprotein receptors are reminiscent of the effects mediated by peroxisome proliferator-activated receptor (PPARgamma) ligands.
Atherosclerosis, 2008
Previously we have shown that intestinal cells efficiently take up oxidized fatty acids (OxFAs) a... more Previously we have shown that intestinal cells efficiently take up oxidized fatty acids (OxFAs) and that atherosclerosis is increased when animals are fed a high cholesterol diet in the presence of oxidized linoleic acid. Interestingly, we found that in the absence of dietary cholesterol, the oxidized fatty acid fed low-density lipoprotein (LDL) receptor negative mice appeared to have lower plasma triglyceride (TG) levels as compared to animals fed oleic acid. In the present study, we fed C57BL6 mice a normal mice diet supplemented with oleic acid or oxidized linoleic acid (at 18 mg/animal/ day) for 2 weeks. After the mice were sacrificed, we measured the plasma lipids and collected livers for the isolation of RNA. The results showed that while there were no significant changes in the levels of total cholesterol and high-density lipoprotein cholesterol (HDLc), there was a significant decrease (41.14%) in the levels of plasma TG in the mice that were fed oxidized fatty acids.
Atherosclerosis, 2010
Background-Atherosclerosis is a chronic inflammatory disease associated with the accumulation of ... more Background-Atherosclerosis is a chronic inflammatory disease associated with the accumulation of oxidized lipids in arterial lesions. Recently we studied the degradation of peroxidized linoleic acid and suggested that oxidation is an essential process that results in the generation of terminal products, namely mono-and dicarboxylic acids that may lack the pro-atherogenic effects of peroxidized lipids. In continuation of that study, we tested the effects of azelaic acid (AzA), one of the end products of linoleic acid peroxidation, on the development of atherosclerosis using low density lipoprotein receptor knockout (LDLr −/− ) mice.
Antioxidants & Redox Signaling, 2009
The decomposition of peroxidized lipids of low-density lipoprotein (LDL) has been suggested to be... more The decomposition of peroxidized lipids of low-density lipoprotein (LDL) has been suggested to be involved in atherosclerosis. In this study, an in vitro system with 13-hydroperoxylinoleic acid (13-HPODE) was used to determine the effects of antioxidants on its decomposition. Decomposition of 13-HPODE was not affected by a-tocopherol, several other antioxidants, or antioxidant enzymes. Moreover, the inclusion of a-tocopherol during the decomposition of 13-HPODE resulted in an accumulation of aldehydes. Further oxidation of aldehydes to carboxylic acids by a number of oxidases was prevented by a-tocopherol. Conversely, the formation of carboxylic acids may be conducive to plaque stabilization via immunomodulation, rapid degradation, and by calcium sequestration. Thus, the inhibition of formation of carboxylic acids could be a serious deleterious effect of antioxidant treatment. In contrast, a-keto acids, like pyruvic acid, promoted the conversion of 13-HPODE to 13-hydroxylinoleic acid (13-HODE) by readily undergoing decarboxylation into acetate. These observations suggest that agents that promote the reduction of lipid peroxides into lipid hydroxides could be far more effective in treating cardiovascular diseases as opposed a-tocopherol-like antioxidants that could affect additional steps in the oxidation cascade. Antioxid. Redox Signal. 11, 1237-1248.
The Journal of Heart and Lung Transplantation, 2008
Our results reflect differential roles of VEGF isoforms with regards to EC permeability, clarifyi... more Our results reflect differential roles of VEGF isoforms with regards to EC permeability, clarifying the factors associated with the development of native atherosclerosis and AV. Identification of novel therapeutic strategies by selectively targeting specific VEGF isoforms may be possible.