RESUMEN
OBJECTIVE: Inflammation is associated with the disruption of the aortic media and appears to play a fundamental role in the progression and development of abdominal aortic aneurysm (AAA). Haptoglobin (Hp) is a genetically determined acute phase protein, the synthesis of which is increased during inflammation. This study was designed to investigate both phenotype and plasma levels of Hp in patients with AAA. METHODS: Patients with documented AAA who were admitted for elective open repair operation or endograft stent implantation, and non-AAA subjects admitted for coronary arteriography, but found to have normal or insignificant coronary artery disease, were included in the study. Plasma Hp levels were determined using a standard specific enzyme-linked immunosorbent assay, while Hp phenotype was determined by native polyacrylamide gel electrophoresis. Total cholesterol, high density lipoprotein, low density lipoprotein, and triglyceride levels were analyzed enzymatically, and C-reactive protein was analyzed by immunochemistry. RESULTS: Forty-five patients with AAA and 49 non-AAA subjects were included. The Hp 2-2 phenotype was more predominant in AAA patients compared with non-AAA subjects, but this difference was not significant (67% vs 47%; P = .141), while plasma Hp concentrations were significantly higher in AAA patients (237 ± 144 vs 163 ± 86 ng/mL; P = .024). Further analysis revealed that plasma Hp concentrations were significantly higher in AAA patients with the 2-2 phenotype compared with corresponding non-AAA subjects (238 ± 144 vs 163 ± 86 ng/mL;P = .024). CONCLUSIONS: Our findings suggest that plasma Hp concentrations are elevated in patients with AAA, particularly those with the Hp 2-2 phenotype.
Asunto(s)
Aneurisma de la Aorta Abdominal/inmunología , Haptoglobinas/análisis , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Aneurisma de la Aorta Abdominal/sangre , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Colesterol/sangre , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Masculino , Fenotipo , Taiwán , Triglicéridos/sangre , Regulación hacia ArribaRESUMEN
BACKGROUND AND PURPOSE: It is well documented that oxidized low-density lipoproteins (LDLs) can stimulate human vascular endothelial cells to produce monocyte chemoattractant protein-1 (MCP-1). Vitamin C is known to be an important antioxidant for vasodilatation. The purpose of this study was to determine whether pretreatment with vitamin C could protect against oxidized-LDL-induced expression of MCP-1 in cultured human umbilical vein endothelial cells (HUVECs). METHODS: Cultured HUVECs were used for desired experiments before passage 4. Lysophosphatidylcholine (lysoPC), an oxidized component of LDL, was designated as the stimulator for MCP-1 synthesis from cultured HUVECs. MCP-1 concentrations in the cultured media were determined by enzyme-linked immunosorbent assay. MCP-1 RNA was evaluated by a semi-quantitative reverse transcriptase-polymerase chain reaction. RESULTS: HUVECs secreted MCP-1 within 30 minutes after exposure to 50 microM lysoPC. Compared with samples treated with lysoPC alone, pretreatment with vitamin C in concentrations of 50, 100, 150, and 200 microM, reduced levels of MCP-1 in the culture medium by 44%, 51%, 60%, and 67%, respectively, while levels of MCP-1 mRNA decreased by 15%, 18%, 80%, and 82%, respectively. CONCLUSIONS: Our findings imply that pretreatment with vitamin C can suppress lysoPC-induced expression and secretion of MCP-1 in cultured HUVECs. Therefore, vitamin C is protective against lysoPC-mediated inflammatory insults to the vascular endothelium in vitro.
Asunto(s)
Ácido Ascórbico/farmacología , Quimiocina CCL2/metabolismo , Depuradores de Radicales Libres/farmacología , Lisofosfatidilcolinas/antagonistas & inhibidores , Lisofosfatidilcolinas/farmacología , Animales , Bovinos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Humanos , ARN Mensajero/metabolismo , Venas Umbilicales/citología , Venas Umbilicales/metabolismoRESUMEN
BACKGROUND: Paraoxonase (PON), a high density lipoprotein (HDL)-associated enzyme, is capable of inhibiting low density lipoprotein (LDL) oxidation by destroying the biologically active phospholipids in oxidatively modified LDL. An increased risk of coronary artery disease (CAD) has shown to associate with polymorphisms of PON gene (PON1) in different population. The risk of CAD associated with the other PON1-like gene, designated PON2, which has a similar function and is structurally related to PON1, is least discussed. A population-based case-control study was conducted to investigate the association between CAD and the polymorphisms at two common codons 148 and 311 of PON2 in the population of Taiwan. METHODS: Totally 364 unrelated, angiographically proved CAD-positive patients (338 male and 26 female) and 337 unrelated, CAD-free control subjects (249 male and 88 female) enrolled in this study. Lipids and lipoproteins profile and the association of PON2 genotypes and allele frequencies were analyzed in all study cohorts. RESULTS: The plasma levels of HDL-cholesterol and apoA-I were significantly lower in patients with CAD than in control subjects (both p = 0.0001). There was no difference in the genotype frequency distribution at codon 148 of PON2 between CAD patients and the controls. However, age-, sex- and diabetes-adjusted odds ratios for individuals with the SS genotype of the codon 311 polymorphism (Cys --> Ser, PON2*C allele --> PON2*S allele) showed a 4.6-fold higher risk of CAD (95% CI = 1.6-15.3, p = 0.006) they ran. Also, in the control subjects, PON2*C allele carriers (CC and CS genotypes) had higher plasma levels of HDL than cases with the SS genotypes (p = 0.035 and p = 0.012, respectively). CONCLUSIONS: Our data implicate that the genotypic variation at codon 311 of PON2 contributes to the susceptibility of CAD in the population of Taiwan.