Autoantibodies to oxidized low density lipoprotein have been shown to be an independent predictor of the progression of carotid atherosclerosis. This study examines the relationship between low density lipoprotein fatty acid composition and autoantibodies to both malondialdehyde-modified and copper-oxidized low density lipoprotein in non-diabetic patients with (n = 17), and without (n = 18), definite evidence of previous myocardial infarction. The third group were non-insulin-dependent diabetic patients with no evidence of atherosclerosis (n = 15) and the fourth group were patients with non-insulin-dependent diabetes (n = 17) who had definite evidence of previous myocardial infarction. Fatty acids were measured by gas-liquid chromatography. Antibodies to malondialdehyde-modified low density lipoprotein and copper-oxidized low density lipoprotein were determined by an ELISA method. Autoantibodies to copper-oxidized low density lipoprotein were significantly higher in the non-diabetic patients with heart disease when compared to any other group (p < 0.05). Autoantibodies to malondialdehyde-modified low density lipoprotein were significantly higher in the non-diabetic subjects with heart disease and in both diabetic groups compared to non-diabetic subjects without coronary heart disease (p < 0.05). Lineolic acid (%) in low density lipoprotein did not differ between groups but arachidonic acid (%) was significantly lower in both diabetic and non-diabetic patients with coronary heart disease (p < 0.05). The diabetic patients with low antibodies had 39.6 ± 2.2 % polyunsaturated fatty acids in their low density lipoprotein while diabetic patients with high antibodies had 46.7 ± 1.2 % polyunsaturates in their low density lipoprotein (p < 0.01). This study confirms the association between antibodies to oxidized low density lipoprotein and coronary heart disease and shows raised low density lipoprotein antibody levels in diabetic patients with and without demonstrable atherosclerosis. In the diabetic patients, those with high antibody levels had high polyunsaturated fatty acid levels in their LDL suggesting a possible role for dietary intervention. © 1997 John Wiley & Sons, Ltd.

This study examines the activity of two key enzymes of reverse cholesterol transport, cholesterol ester transfer protein (CETP) and lecithin:cholesterol acyl transferase (LCAT) in 21 patients with non-insulin dependent diabetes mellitus (NIDDM) and 21 control subjects. Serum CETP was assessed by measuring plasma-mediated cholesteryl ester transfer between pooled exogenous lipoprotein with endogenous LCAT inhibited — an estimate of CETP mass. CETP activity was determined as cholesteryl ester transfer in the presence of the patients' lipoproteins and LCAT (endogenous assay). LCAT activity was determined in the same assay. There was no significant difference in CETP mass between the diabetic and non-diabetic subjects and there was no correlation between CETP mass and LCAT activity. Using the endogenous lipoprotein assay, CETP was elevated in serum from diabetic patients compared to control subjects (10.05 ± 1.89 vs. 5.50 ± 0.53 nmol/ml/h P < 0.05). LCAT was also increased in the diabetic patients (53.63 ± 4.70 vs. 41.22 ± 3.40 nmol/ml/h P < 0.05). Serum free cholesterol from diabetic and control subjects correlated with CETP activity measured using endogenous lipoprotein assay (r = 0.77, P < 0.001 and r = 0.82, P < 0.001), and also with LCAT activity (r = 0.76, P < 0.01 and r = 0.79, P < 0.01). There was a negative correlation between CETP activity with the endogenous lipoprotein assay and serum high density lipoprotein (HDL) cholesterol in the diabetic patients (r = −0.38, P < 0.01), but not in control subjects. In a subgroup of 10 control subjects, there was a positive correlation between LCAT activity and apolipoprotein (apo) A-I (r = 0.49, P < 0.05) and apo A-II (r = 0.51, P < 0.05) and also between CETP activity (endogenous assay) and apo A-I (r = 0.87, P = 0.001) and apo A-II (r = 0.63, P < 0.05). No relationship was observed between CETP activity and apo A-I or apo A-II in the diabetic subjects. Thus, serum CETP mass was normal in Type 2 diabetes but CETP activity (endogenous assay) was increased and was related to free cholesterol levels and LCAT activity in both diabetic and non-diabetic subjects.

Conference Article| February 01 1994 Effects of low density lipoprotein of varying composition on cholesterol levels in human monocyte-derived macrophages SEAN P. McBRINN; SEAN P. McBRINN 1Department of Biochemistry, Royal College of Surgeons in Ireland, Dublin 2 Search for other works by this author on: This Site PubMed Google Scholar ALAN H. JOHNSON; ALAN H. JOHNSON 1Department of Biochemistry, Royal College of Surgeons in Ireland, Dublin 2 Search for other works by this author on: This Site PubMed Google Scholar GERALD H. TOMKIN; GERALD H. TOMKIN *Department of Metabolic Medicine, The Adelaide Hospital, Dublin 8, Ireland Search for other works by this author on: This Site PubMed Google Scholar PATRICK B. COLLINS PATRICK B. COLLINS 1Department of Biochemistry, Royal College of Surgeons in Ireland, Dublin 2 Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1994) 22 (1): 36S. https://doi.org/10.1042/bst022036s Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation SEAN P. McBRINN, ALAN H. JOHNSON, GERALD H. TOMKIN, PATRICK B. COLLINS; Effects of low density lipoprotein of varying composition on cholesterol levels in human monocyte-derived macrophages. Biochem Soc Trans 1 February 1994; 22 (1): 36S. doi: https://doi.org/10.1042/bst022036s Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1994 Biochemical Society1994 Article PDF first page preview Close Modal You do not currently have access to this content.

The role of adrenergic mechanisms in the regulation of cholesterol metabolism was investigated by studying the effects of 6‐hydroxydopamine (6‐OHDA) on serum cholesterol levels and on the activities of 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMGCoA) reductase, acyl coenzyme A: cholesterol‐O‐acyltransferase (ACAT) in the livers and intestines, and cholesterol 7α‐hydroxylase in the livers of male New Zealand White rabbits. Total serum cholesterol levels were significantly reduced (P < 0.01) in 6‐OHDA‐treated animals. This was reflected in the very low density lipoprotein, low density lipoprotein and high density lipoprotein fractions. The reduction in lipoprotein cholesterol levels reflected reduced cholesterol proportions in the lipoprotein fractions. The 6‐OHDA‐treated animals also had significantly lower activities of intestinal (P < 0.001) and hepatic (P < 0.01) HMGCoA reductase. The specific activities of intestinal ACAT, hepatic ACAT and cholesterol 7α‐hydroxylase were comparable in both groups. In contrast to the results observed in vivo, 6‐OHDA did not have any in vitro effect on cholesterol biosynthesis in cultured human leucocytes. This latter finding suggests that the effects of 6‐OHDA on cellular cholesterol biosynthesis in vivo are indirect, possibly resulting from the known toxic effect of this drug in sympathetic nerve terminals, and imply a potential role for the sympathetic nervous system in the regulation of cellular cholesterol biosynthesis in vivo.

Serum lipoproteins and key hepatic and intestinal enzymes regulating cholesterol synthesis, esterification and catabolism, namely 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, acyl coenzyme A: cholesterol-o-acyltransferase (ACAT) and cholesterol 7 alpha-hydroxylase respectively, were compared in two hypercholesterolaemic rabbit models - the cholesterol-fed animal and the hypercholesterolaemic diabetic animal. Hypercholesterolaemia in the cholesterol-fed animals was reflected in the VLDL and LDL fractions, whereas VLDL and HDL2 cholesterol levels were elevated in the diabetic animals. The lipoproteins of the cholesterol-fed animals were enriched with cholesterol but the lipoprotein fractions in the diabetic animals were enriched with triacylglycerol. While hepatic HMGCoA reductase activity was significantly reduced in both groups, the activities of hepatic ACAT and cholesterol 7 alpha-hydroxylase were significantly increased in the cholesterol-fed animals and significantly reduced in the diabetic animals compared with controls. In the intestine, the activity of HMGCoA reductase was increased and ACAT reduced in the diabetic animals. By contrast, in the cholesterol-fed group. HMGCoA reductase activity was lower and ACAT activity was higher in comparison with the control group. These differences in lipoproteins and cellular cholesterol metabolism between the hypercholesterolaemic rabbit models may explain the differences in susceptibility to atherosclerosis, previously reported in these two animal models.

The effect of diabetes control on the activities of hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase), cholesterol acyltransferase (ACAT), and phenol 2-monooxygenase, the major enzymes regulating cholesterol metabolism, was determined in alloxan-induced diabetic rabbits, and the results obtained were correlated with lipid and lipoprotein levels. Although intestinal HMG-CoA reductase activity was significantly increased (P < 0.001) in poorly controlled compared with moderately controlled diabetic rabbits, there was a significant reduction in the activities of intestinal ACAT (P < 0.01), hepatic HMG-CoA reductase (P < 0.05) and ACAT (P < 0.001), and phenol 2-monooxygenase (P < 0.01). The poorly controlled animals were hypercholesterolemic (P < 0.01), and this was reflected in the very-low-density and high-density lipoprotein fractions. Serum cholesterol levels in the nondiabetic and moderately controlled diabetic groups were similar. This increase in intestinal HMG-CoA reductase activity in the poorly controlled diabetic animals occurred in the absence of hyperphagia. Although abnormalities in cellular cholesterol metabolism could be partly responsible for the alterations in serum cholesterol levels in diabetes, the precise mechanisms underlying these enzymatic changes have yet to be elucidated.

This study investigates the lipoprotein abnormalities in the alloxan-diabetic rabbit maintained on a standard chow diet. Poorly-controlled diabetic rabbits had elevated levels of triglyceride and phospholipid (reflected in all lipoprotein fractions) and cholesterol (reflected in the very low density and high density lipoprotein fractions) compared with well-controlled and non-diabetic rabbits. The importance of diabetic control in these changes was emphasized by the observation of a positive correlation between weight loss and serum triglyceride (rs = 0.62, p less than 0.02), cholesterol (rs = 0.65, p less than 0.01) and phospholipid (rs = 0.56, p less than 0.05). The lipoprotein fractions of the poorly-controlled rabbits were enriched with triglyceride.

Conference Article| April 01 1988 Lipoprotein cholesterol levels in hypercholesterolaemic rabbits N. O'MEARA; N. O'MEARA 1Department of Biochemistry, The Royal College of Surgeons in Ireland, Dublin 2 and Department of Metabolic Medicine, The Adelaide Hospital, Dublin 8, Republic of Ireland Search for other works by this author on: This Site PubMed Google Scholar L. O'DONNELL; L. O'DONNELL 1Department of Biochemistry, The Royal College of Surgeons in Ireland, Dublin 2 and Department of Metabolic Medicine, The Adelaide Hospital, Dublin 8, Republic of Ireland Search for other works by this author on: This Site PubMed Google Scholar D. OWENS; D. OWENS 1Department of Biochemistry, The Royal College of Surgeons in Ireland, Dublin 2 and Department of Metabolic Medicine, The Adelaide Hospital, Dublin 8, Republic of Ireland Search for other works by this author on: This Site PubMed Google Scholar P. B. COLLINS; P. B. COLLINS 1Department of Biochemistry, The Royal College of Surgeons in Ireland, Dublin 2 and Department of Metabolic Medicine, The Adelaide Hospital, Dublin 8, Republic of Ireland Search for other works by this author on: This Site PubMed Google Scholar A. H. JOHNSON; A. H. JOHNSON 1Department of Biochemistry, The Royal College of Surgeons in Ireland, Dublin 2 and Department of Metabolic Medicine, The Adelaide Hospital, Dublin 8, Republic of Ireland Search for other works by this author on: This Site PubMed Google Scholar G. H. TOMKIN G. H. TOMKIN 1Department of Biochemistry, The Royal College of Surgeons in Ireland, Dublin 2 and Department of Metabolic Medicine, The Adelaide Hospital, Dublin 8, Republic of Ireland Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1988) 16 (2): 200–201. https://doi.org/10.1042/bst0160200a Article history Received: September 23 1987 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation N. O'MEARA, L. O'DONNELL, D. OWENS, P. B. COLLINS, A. H. JOHNSON, G. H. TOMKIN; Lipoprotein cholesterol levels in hypercholesterolaemic rabbits. Biochem Soc Trans 1 April 1988; 16 (2): 200–201. doi: https://doi.org/10.1042/bst0160200a Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: VLDL, very low density lipoprotein, LDL, low density lipoprotein, HDL, high density lipoprotein This content is only available as a PDF. © 1988 Biochemical Society1988 Article PDF first page preview Close Modal You do not currently have access to this content.

Conference Article| April 01 1987 Free-oxygen radical generation in ischaemic rat intestine using a tissue section chemiluminescent assay JOHN P. LAVELLE; JOHN P. LAVELLE 1Department of Biochemistry, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin 2, Ireland Search for other works by this author on: This Site PubMed Google Scholar PATRICK B. COLLINS; PATRICK B. COLLINS 1Department of Biochemistry, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin 2, Ireland Search for other works by this author on: This Site PubMed Google Scholar ALAN H. JOHNSON; ALAN H. JOHNSON 1Department of Biochemistry, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin 2, Ireland Search for other works by this author on: This Site PubMed Google Scholar THOMAS F. GOREY THOMAS F. GOREY 1Department of Biochemistry, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin 2, Ireland Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1987) 15 (2): 289. https://doi.org/10.1042/bst0150289 Article history Received: September 26 1986 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation JOHN P. LAVELLE, PATRICK B. COLLINS, ALAN H. JOHNSON, THOMAS F. GOREY; Free-oxygen radical generation in ischaemic rat intestine using a tissue section chemiluminescent assay. Biochem Soc Trans 1 April 1987; 15 (2): 289. doi: https://doi.org/10.1042/bst0150289 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: SOD, superoxide dismutase, DMSO, dimethyl sulphoxide, cordycepin, 3′-deoxyadenosine This content is only available as a PDF. © 1987 Biochemical Society1987 Article PDF first page preview Close Modal You do not currently have access to this content.