作者机构:
[Song lan] Cent S Univ, Xiangya Sch Med, Dept Pathophysiol, Changsha 410008, Hunan, Peoples R China.;[Xu Zhao-jun] Hunan Univ Tradit Chinese Med, Cardiothorac Surg Affiliated Hosp 1, Changsha 41007, Hunan, Peoples R China.;[Zhang Cai-ping; Tian ying] Nanhua Univ, Coll Life Sci, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Song, L ] ;Cent S Univ, Xiangya Sch Med, Dept Pathophysiol, 110 Xiangya Rd, Changsha 410008, Hunan, Peoples R China.
关键词:
fibroblast;adrenaline;bFGF;TGF-beta 1
摘要:
Adrenaline has been shown to modulate proliferation of mouse fibroblasts, adventitial fibroblasts and synovial B (fibroblasts-like) cells. However, little is known about the response of cultured human hypertrophic scar fibroblasts to adrenaline. In this study, we investigated cell proliferation and involved mechanisms in hypertrophic scar fibroblasts in response to adrenaline. Population doubling time (PDT) assay and MTT assay were performed to determine the cell proliferation and cell viability, respectively. The expression of bFGF and TGF-beta 1 was measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA). The results showed that adrenaline inhibited proliferation of normal and hypertrophic scar fibroblasts in a dose-dependent manner. Moreover, adrenaline up-regulated the expression of bFGF and down-regulated the expression of TGF-beta 1 in normal and hypertrophic scar fibroblasts. Interestingly incubation with the a receptor antagonist regitine indicated that adrenaline mediated inhibition of cell proliferation and regulation of TGF-beta 1 and bFGF in cultured normal and hypertrophic scar fibroblasts were mediated by the a receptor. These studies suggest that adrenaline inhibits proliferation and alters the expression of TGF-beta 1 and bFGF in human hypertrophic scar fibroblast involving an a receptor mediated pathway.
摘要:
Alterations in plasma apolipoproteins levels can influence the composition, content, and distribution of plasma lipoproteins that affect the risk of atherosclerosis. This study assessed the relationship between plasma apolipoproteins levels, mainly apoAI, and HDL subclass distribution. The contents of plasma HDL subclasses were determined by two-dimensional gel electrophoresis coupled with immunodetection in 545 Chinese subjects. Compared with a low apoAI group, the contents of all HDL subclasses increased significantly both in middle and high apoAI group, and the contents of large-sized HDL(2b) increased more significantly relative to those of small-sized prebeta(1)-HDL in a high apoAI group. When apoAI and HDL-C levels increased simultaneously, in comparison to a low apoAI along with HDL-C concentration group, a significant increase (116%) was shown in HDL2b but only a slight increase (26%) in prebeta1-HDL. In addition, Pearson correlation analysis revealed that apoAI levels were positively and significantly correlated with all HDL subclasses. Multiple liner regression demonstrated that the apoAI concentrations were the most powerful predictor for HDL subclass distribution. With the elevation of apoAI concentrations, the contents of all HDL subclasses increased successively and significantly, especially, an increase in large-sized HDL(2b). Further, when apoAI and HDL-C concentrations increased simultaneously, the shift to larger HDL size was more obvious. Which, in turn, indicated that HDL maturation might be enhanced and, the reverse cholesterol transport might be strengthened along with apoAI levels which might be a more powerful factor influencing the distribution of HDL subclasses.
期刊:
International Journal of Cardiology,2007年120(3):331-337 ISSN:0167-5273
通讯作者:
Fu, Mingde
作者机构:
[Fu, Mingde] Sichuan Univ, W China Hosp, Lab Endocrinol & Metab, Chengdu 610041, Peoples R China.;Nanhua Univ, Dept Biochem & Mol Biol, Hengyang, Hunan, Peoples R China.;Hoist Grp Postdoctoral Work Stn, Chengdu, Sichuan, Peoples R China.
通讯机构:
[Fu, Mingde] S;Sichuan Univ, W China Hosp, Lab Endocrinol & Metab, Chengdu 610041, Peoples R China.
关键词:
2-Dimensional gel electrophoresis-immunodetection;Combined hyperlipidemia;HDL subclasses;Hypercholesterolemia
摘要:
Background: Alterations in plasma lipid levels can influence the composition, content, and distribution of plasma lipoprotein subclasses that effect atherosclerosis risk. Hypercholesterolemia and combined hyperlipidemia are common forms of atherogenic dyslipoproteinemia. This study evaluates the alterations of high-density lipoprotein (HDL) subclasses in hypercholesterolemic and combined hyperlipidemic subjects. Methods: Apolipoprotein A-I contents of plasma HDL subclasses were quantitated by 2-dimensional gel electrophoresis in 242 normolipidemic subjects, 66 hypercholesterolemic subjects and 59 combined hyperlipidemic subjects. Results: Compared with the normolipidemic subjects, apolipoprotein A-I contents of small-sized pre-beta(1)-HDL, HDL3c, HDL(3b)and HDL(3a)were significantly higher in both hypercholesterolemic subjects (p <.01, p <.05, p <.01 and p <.05, respectively) and combined hyperlipidemic subjects (p <.0l,p <.05,p <.01 and p <.01, respectively). In contrast, apolipoprotein A-I contents of large-sized HDL2a and HDL2b were significantly lower in hypercholesterolemic subjects (p <.05 and p <.01, respectively) as well as combined hyperlipidemic subjects (p <.01 and p <.01, respectively). In addition, pre-beta(1)-HDL increased significantly (p <.05) while HDL2a and HDL2b decreased significantly (p <.05 and p <.0 1, respectively) in combined hyperlipidemic group versus hypercholesterolemic subjects. With the elevation of triglyceride levels, pre-beta(1)-HDL, and HDL3a. increased successively, however, HDL2a and HDL2b decreased successively in subjects with total cholesterol levels greater than 240 mg/dl. Conclusions: The particle size of HDL shifted towards smaller size in hypercholesterolemic subjects, and that the shift was more prominent in combined hyperlipidemic subjects. The alternations mentioned above indicate that HDL maturation might be abnormal, and reverse cholesterol transport (RCT) might be weakened. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
作者机构:
[Fu, MD] Sichuan Univ, W China Sch Preclin & Forens Med, Apolipoprot Res Unit, Dept Biochem & Mol Biol, Chengdu 610041, Peoples R China.;Nanhua Univ, Dept Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.;Hoist Grp Postdoctoral Work Stn, Chengdu 610075, Sichuan, Peoples R China.
通讯机构:
[Fu, MD] S;Sichuan Univ, W China Sch Preclin & Forens Med, Apolipoprot Res Unit, Dept Biochem & Mol Biol, Chengdu 610041, Peoples R China.
关键词:
Gene polymorphism;HDL subclasses;Hyperlipidemia;Lipoprotein lipase;Two-dimensional gel electrophoresis-immunodetection
摘要:
Background: Different high-density lipoprotein (HDL) subclasses have distinct but interrelated metabolic functions. HDL directly influences the atherogenic process, and changes in HDL subclasses distribution may be related to the incidence and prevalence of atherosclerosis. Lipoprotein lipase (LPL) is an important enzyme for hydrolysis of triglyceride-rich lipoproteins, and its activity is positively correlated with the plasma HDL cholesterol level. LPL gene HindIII polymorphism has been found associated with variations in lipid levels, but the impact on HDL subclasses distribution is less clearly established. Methods: The relative apolipoprotein (apo) A-I contents (% apoA-I) of plasma HDL subclasses were determined by two-dimensional gel electrophoresis coupled with immunodetection and LPL gene HindIII polymorphism was assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 173 hyperlipidemic and 155 normolipidemic subjects. Results: The frequencies of 495TT genotype and allele T were the highest both in the hyperlipidemic and control groups. Compared with the control group, the frequency of 495TT genotype was higher, while the frequencies of 495TG and 495GG genotypes were significantly lower (P < 0.05) in the hyperlipidemic group. Two-dimensional gel electrophoresis and immunodetection showed that HDL subclasses distribution was altered in hyperlipidemia, and had a general shift toward smaller size. Compared with the control group, the hyperlipidemic group had significantly higher relative apoA-I contents of pre beta(1)-HDL, pre beta(2)-HDL, HDL3b and HDL3(a) (P < 0.05) and lower HDL2a and HDL2b levels (P < 0.001). In the hyperlipidernic group, allele T carriers' frequency was higher than that in the control group (P < 0.05), and the genotype of 495TT showed higher levels of plasma TG, apoB100, TG/HDL-C ratio, relative apoA-I contents of pre beta(1)-HDL, HDL3b and lower HDL2a, HDL2b compared with that of the 495GG genotype subgroup (P < 0.05). In the control group, the genotype of 495TT had higher plasma TG, HDL3c and lower HDL2a compared with that of 495GG subgroup (P < 0.05). Conclusions: The 495TT genotype of LPL gene HindIII polymorphism was associated with changes of HDL subclasses distribution in Chinese population with hyperlipidemia. The particle size of HDL shifted toward smaller, which, in turn, indicated that RCT might be weakened and HDL maturation might be abnormal in hyperlipidemic subjects with 495TT genotype. (c) 2005 Elsevier B.V. All rights reserved.
摘要:
The object of this study was to investigate the characteristics of lipid metabolism in obese subjects, with particular emphasis on the alteration of HDL subclass contents and distributions. A population of 581 Chinese individuals was divided into four groups (25 underweight subjects, 288 of desirable weight, 187 overweight, and 45 obese) according to body mass index (BMI). Apoprotein A-1 (apoA-1) contents of plasma HDL subclasses were determined by 2-D gel electrophoresis associated with an immunodetection method. The concentrations of TG and the apoA-I content of pre-beta(1)-HDL were significantly higher (P < 0.01 and P < 0.01, respectively), but the levels of HDL cholesterol, and the apoA-1 contents of HDL2a and HDL2b were significantly lower (P < 0.01, P < 0.05, and P < 0.01, respectively) in obese subjects than in subjects having a desirable weight. Moreover, with the elevation of BMI, small-sized pre-beta 1-HDL increased gradually and significantly, whereas large-sized HDL2b decreased gradually and significantly. Meanwhile, the variations in HDL subclass distribution were more obvious with the elevation of TG levels in obese as well as overweight subjects. In addition, Pearson correlation analysis revealed that BMI and TG levels were positively correlated with pre-beta(1)-HDL but negatively correlated with HDL2b. Multiple regression analysis also showed that TG concentrations were associated independently and positively with high pre-beta(1)-HDL and independently and negatively with low HDL2b in obese and overweight subjects. The HDL particle size was smaller in obese and overweight subjects. The shift to smaller size was more obvious with the elevation of BMI and TG, especially TG levels. These observations, in turn, indicated that HDL maturation might be abnormal, and reverse cholesterol transport might be impaired.