Abstract
Disorders of the lipid metabolism may play a role in the genesis of abdominal aorta aneurysm. The present study examined the intravascular catabolism of chylomicrons, the lipoproteins that carry the dietary lipids absorbed by the intestine in the circulation in patients with abdominal aorta aneurysm. Thirteen male patients (72 ± 5 years) with abdominal aorta aneurysm with normal plasma lipid profile and 13 healthy male control subjects (73 ± 5 years) participated in the study. The method of chylomicron-like emulsions was used to evaluate this metabolism. The emulsion labeled with 14C-cholesteryl oleate and ³H-triolein was injected intravenously in both groups. Blood samples were taken at regular intervals over 60 min to determine the decay curves. The fractional clearance rate (FCR) of the radioactive labels was calculated by compartmental analysis. The FCR of the emulsion with ³H-triolein was smaller in the aortic aneurysm patients than in controls (0.025 ± 0.017 vs 0.039 ± 0.019 min-1; P < 0.05), but the FCR of14C-cholesteryl oleate of both groups did not differ. In conclusion, as indicated by the triglyceride FCR, chylomicron lipolysis is diminished in male patients with aortic aneurysm, whereas the remnant removal which is traced by the cholesteryl oleate FCR is not altered. The results suggest that defects in the chylomicron metabolism may represent a risk factor for development of abdominal aortic aneurysm.
Abdominal aortic aneurysm; Lipoproteins; Chylomicrons; Emulsions
Braz J Med Biol Res, March 2007, Volume 40(3) 305-307 (Short Communication)
Lipolysis of emulsion models of triglyceride-rich lipoproteins is altered in male patients with abdominal aorta aneurysm
J.J. Hosni1, C.G. Vinagre1, C. Mady1 and Correspondence and Footnotes R.C. Maranhão1,2
1Laboratório de Metabolismo de Lípides, Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, 2Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP, Brasil
Text
References Correspondence and Footnotes Correspondence and Footnotes Correspondence and Footnotes
Disorders of the lipid metabolism may play a role in the genesis of abdominal aorta aneurysm. The present study examined the intravascular catabolism of chylomicrons, the lipoproteins that carry the dietary lipids absorbed by the intestine in the circulation in patients with abdominal aorta aneurysm. Thirteen male patients (72 ± 5 years) with abdominal aorta aneurysm with normal plasma lipid profile and 13 healthy male control subjects (73 ± 5 years) participated in the study. The method of chylomicron-like emulsions was used to evaluate this metabolism. The emulsion labeled with 14C-cholesteryl oleate and 3H-triolein was injected intravenously in both groups. Blood samples were taken at regular intervals over 60 min to determine the decay curves. The fractional clearance rate (FCR) of the radioactive labels was calculated by compartmental analysis. The FCR of the emulsion with 3H-triolein was smaller in the aortic aneurysm patients than in controls (0.025 ± 0.017 vs 0.039 ± 0.019 min-1; P < 0.05), but the FCR of 14C-cholesteryl oleate of both groups did not differ. In conclusion, as indicated by the triglyceride FCR, chylomicron lipolysis is diminished in male patients with aortic aneurysm, whereas the remnant removal which is traced by the cholesteryl oleate FCR is not altered. The results suggest that defects in the chylomicron metabolism may represent a risk factor for development of abdominal aortic aneurysm.
Abstract
Key words: Abdominal aortic aneurysm, Lipoproteins, Chylomicrons, Emulsions
Text
Abdominal aorta aneurysms (AAA) are mostly of atherosclerotic origin (1) and the classical plasma lipid risk factors for coronary artery disease are involved. However, the metabolism of chylomicrons, lipoproteins that carry dietary fats absorbed by the intestine in the circulation, has not been investigated. Once in the bloodstream, chylomicron triglycerides are degraded by lipoprotein lipase and the resulting chylomicron remnants are then taken-up by the liver. Diminished chylomicron triglyceride breakdown and the accumulation of remnants are linked to coronary artery disease (2-5). However, evaluating this metabolism in human subjects is difficult. Plasma kinetic determination of double-labeled chylomicron-like emulsions is a practical method for the study of chylomicron metabolism: 1) the plasma decay curves of the emulsion triglycerides trace the lipolysis process, and 2) the cholesteryl ester curve traces the remnant removal from plasma.
The study was conducted on 13 patients with AAA (72.1 ± 5.0 years) and 13 healthy control subjects (72.9 ± 4.9 years) confirmed by computed tomography. The protocol was approved by the Ethics Committee of the Hospital of the University of São Paulo Medical School and a written informed consent was obtained from all participant subjects. Body mass index, that has been previously shown to correlate with the plasma kinetics of chylomicrons (6), was similar in the two groups (controls: 25.2 ± 2.5; AAA: 24.3 ± 3.2 kg/m2). The emulsion was prepared by sonication of constituent lipids followed by ultracentrifugation and labeled with 14C-cholesteryl oleate and 3H-triolein. The emulsion was then injected intravenously in the fasting subjects and radioactivity was counted in plasma samples collected over a period of 1 h for plasma fractional clearance rate (FCR) calculation.
There were no differences between groups regarding plasma concentrations of HDL (AAA: 50 ± 13; controls: 50 ± 9 mg/dL), LDL (133 ± 18; 131 ± 16 mg/dL), total cholesterol (203 ± 23; 201 ± 20 mg/dL), and triglyceride (96 ± 33; 106 ± 43 mg/dL), or in plasma concentrations of apolipoprotein A1 (1.40 ± 0.26 and 1.38 ± 0.15 g/L) and apolipoprotein B (1.08 ± 0.14 and 1.05 ± 0.12 g/L). None of the subjects had diabetes mellitus according to the Standards of Medical Care in Diabetes - 2006, American Diabetes Association (7), and plasma glucose levels were similar for the AAA and control groups (96 ± 12 and 99 ± 4 mg/dL, respectively).
Although the frequency of smokers was higher in AAA (3/13) than in controls (0/13), the frequency of arterial hypertension was similar (5/13 and 3/13).
FCR of 3H-triolein was smaller in AAA (0.025 ± 0.017 min-1) than in controls (0.039 ± 0.019 min-1, P < 0.05, Mann-Whitney test), but the 14C-cholesteryl oleate FCR did not differ between groups (0.011 ± 0.011 and 0.018 ± 0.009 min-1). This implies that lipolysis of the emulsion triglycerides is diminished, but the remnant removal is not altered in AAA.
Modification of risk factors for atherosclerosis is a priority in the clinical management of aortic aneurysms (8). In a recent study (9), arterial hypertension and classic lipid risk factors were not determinants of aneurysmal growth, whereas smoking and aneurysm baseline diameter were, highlighting our finding of a novel lipid marker.
In coronary artery disease patients submitted to secondary prevention, diminished lipolysis was an independent predictor of severe angina while remnant removal was not (10). The postprandial increase in plasma triglycerides should impair arterial vasodilator capacity and enhance procoagulant factors. Reduced lipolysis decreases free fatty acids, the natural activator ligands to a subclass peroxisome proliferator-activated receptors. Decreased peroxisome proliferator-activated receptors should increase endothelial production of the proinflammatory tumor necrosis factor-a and vascular cell adhesion molecule-1 (11,12). In conclusion, a disturbance of triglyceride-rich lipoprotein lipolysis and not remnant clearance is related to AAA.
Address for correspondence: R.C. Maranhão, Laboratório de Metabolismo de Lípides, InCor, HC, FM, USP, Av. Dr. Eneas C. Aguiar, 44, 1º Subsolo, Bloco II, Sala 21, 05403-000 São Paulo, SP, Brasil. Fax: +55-11-3063-0779. E-mail: ramarans@usp.br
Publication supported by FAPESP. Received July 31, 2006. Accepted January 12, 2007.
- 1. Reed D, Reed C, Stemmermann G, Hayashi T. Are aortic aneurysms caused by atherosclerosis? Circulation 1992; 85: 205-211.
- 2. Groot PH, van Stiphout WA, Krauss XH, Jansen H, van Tol A, van Ramshorst E, et al. Postprandial lipoprotein metabolism in normolipidemic men with and without coronary artery disease. Arterioscler Thromb 1991; 11: 653-662.
- 3. Karpe F, Steiner G, Uffelman K, Olivecrona T, Hamsten A. Postprandial lipoproteins and progression of coronary atherosclerosis. Atherosclerosis 1994; 106: 83-97.
- 4. Maranhao RC, Feres MC, Martins MT, Mesquita CH, Toffoletto O, Vinagre CG, et al. Plasma kinetics of a chylomicron-like emulsion in patients with coronary artery disease. Atherosclerosis 1996; 126: 15-25.
- 5. Weintraub MS, Grosskopf I, Rassin T, Miller H, Charach G, Rotmensch HH, et al. Clearance of chylomicron remnants in normolipidaemic patients with coronary artery disease: case control study over three years. BMJ 1996; 312: 936-939.
- 6. Oliveira MR, Maranhao RC. Plasma kinetics of a chylomicron-like emulsion in normolipidemic obese women after a short-period weight loss by energy-restricted diet. Metabolism 2002; 51: 1097-1103.
- 7. American Diabetes Association. Standards of medical care in diabetes - 2006. Diabetes Care 2006; 29 (Suppl 1): S4-S42.
- 8. Simoni G, Gianotti A, Ardia A, Baiardi A, Galleano R, Civalleri D. Screening study of abdominal aortic aneurysm in a general population: lipid parameters. Cardiovasc Surg 1996; 4: 445-448.
- 9. Brady AR, Thompson SG, Fowkes FG, Greenhalgh RM, Powell JT. Abdominal aortic aneurysm expansion: risk factors and time intervals for surveillance. Circulation 2004; 110: 16-21.
- 10. Sposito AC, Lemos PA, Santos RD, Hueb W, Vinagre CG, Quintella E, et al. Impaired intravascular triglyceride lipolysis constitutes a marker of clinical outcome in patients with stable angina undergoing secondary prevention treatment: a long-term follow-up study. J Am Coll Cardiol 2004; 43: 2225-2232.
- 11. Hill MR, Clarke S, Rodgers K, Thornhill B, Peters JM, Gonzalez FJ, et al. Effect of peroxisome proliferator-activated receptor alpha activators on tumor necrosis factor expression in mice during endotoxemia. Infect Immun 1999; 67: 3488-3493.
- 12. Marx N, Sukhova GK, Collins T, Libby P, Plutzky J. PPARalpha activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells. Circulation 1999; 99: 3125-3131.
Correspondence and Footnotes
Publication Dates
-
Publication in this collection
12 Feb 2008 -
Date of issue
Mar 2007
History
-
Received
31 July 2006 -
Accepted
12 Jan 2007