成纤维细胞生长因子研究进展
作者：关德明 尹兆波
单位：150001 黑龙江省哈尔滨市，哈尔滨医科大学第一临床医学院心血管研究所
关键词：
中国煤炭工业医学杂志000403 本文较全面深刻地阐述了成纤维细胞生长因子生成、释放机制及其影响因素，以及促进动脉粥样硬化形成和发展，血管生长和重塑，干滑肌细胞迁移和增殖的病理性作用和临床意义。
1成纤维细胞
心脏是由心肌细胞和非心肌细胞(成纤维细胞，平滑肌细胞-SMC和血管内皮细胞-VEC)组成，成纤维细胞约占心脏非心肌细胞的2/3，虽然出生后心肌细胞马上丧失增殖能力，但非心肌细胞仍然增殖，甚至在成人心脏。当心脏暴露于各种压力时.例如血液动力学超负荷、心肌梗死、心肌细胞体积增大时，心脏成纤维细胞数量增加，并产生细胞外基质蛋白，如胶原蛋白和纤维蛋白。基质使心肌细胞之间互相联接，维持心肌细胞排列。心脏成纤维细胞影响心肌细胞生成和功能[1,2]。血管紧张素Ⅱ(AngⅡ)刺激心脏成纤维细胞增殖，导致细胞胶原蛋白基因，纤维蛋白基因和整合素基因表达。在心脏成纤维细胞，AngⅡ通过G蛋白的Gby亚单位和酪氨酸激酶激活信号调节激酶。当10-6mol/LAngⅡ加人新生鼠的心脏成纤细胞培养基中，胸腺嘧啶脱氧核苷进入细胞增加40%，这种AngⅡ诱导的增加可被AT1受体拮抗剂(CV-11974)抑制，但不能被AT2受体拮抗剂(PD-123319)抑制[1]。
, http://www.100md.com
酪氨酸激酶和信号调节激酶在AngⅡ诱导的心脏成纤维细胞DNA合成中起关键作用。当心脏暴露于各种损伤时，例如：心肌梗死、心肌炎和心肌肥厚等，心脏成纤维细胞增加细胞外基质蛋白(ECM)的生成。AngⅡ通过AT1受体激活心脏成纤维细胞酪氨酸激酶并增加其DNA合成[1,3]。
在组织修复部位，心肌成纤维细胞对胶原蛋白聚集起主要作用。有人认为：细胞内游离钙增加也与成纤维细胞增殖有关[4,5]。
2成纤维细胞生长因子(FGF)(全文详见PDF)……
参考文献：
[1]Yunzeng Z,Issei K,Jsutomu Y.et al. Cell-Type-Specific Ang II Evoked Signal Transduction Pathways. Circ Res. 1998,82:337.
, 百拇医药
[2]Jingsheng Z,Lydia ON,Xilin L,et al. Stimulation of P2Y receptors Activates c-fos Gene Expression and inhibits DNA Synthesis in Cultured Cardiac Fibroblasts. Cardiovascular Research. 1998,37:718.
[3]Marti CK,Jos FMS,Jan WA.et al. AT2 Receptor Blockade Reduces Cardiac Interstitial Cell DNA Synthesis and Cardiac Function after Rat Myocardial Infarction. J Mol Cell Cardiol, 1998,30:425.
[4]J Geoffrey P,Carol MF,Bao T,et al. Coordinated Effects of Fibroblast geowth Factor-2 on Expression of Fibrillar Collagens. Matrix Metalloproteinases and Tissue Inhibitors of Matrix Metalloproteinases by Human VSMCs. Artherioscler Thromb Vasc Biol, 1997,17(3):475.
, 百拇医药
[5]Felix JAR,Yao S and Karl TW. Myocardial Fibrosis Associated with Aldosterone or Ang II Administration:Attenuation by Calcium Channel Blockade. J Mol Cell Cardiol, 1983,30:475.
[6]George CC,William HB,David SG,et al. Mechanical Strain Ti ghtly Controls FGF-2 Release from Cultured Human VSMCs. Circ Res,1997,80:28.
[7]Masahiko Y,Shokei K,Yasukatsu I,et al. Differential Activation of Cardiac c-Jun Amino-Ferminal Kinase and Extracellular signal Regulated Kinase in Ang II Mediated Hypertension. Sirc Res, 1998,83(7):752.
, 百拇医药
[8]Patrik H, Wulf DI, lmo EH,et al. Intramyocardial infusion of FGF-1 mimics ischemic preconditioning in pig myocardium. J Mol Cell Cardiol, 1998,30:867.
[9]Bradley WD,Yijing C.Denis GB,et al. FGF-2 Decreases Metabolic Coupling and Stimulates Phosphorylation as well as Masking of Connexin 43 Epitopes in Cardiac Myocytes. Circ Res, 1996,79:647.
[10]Xinkang W,Calvert L and Eliot HO. Osteopontin expression in platelet-derived growth factor-stimulated vascular smooth muscle cells and carotid artery after balloon angioplasty. Artherioscler Thromb Vasc Biol, 1996,16:1365.
, 百拇医药
[11]Natatya MA.Alexey VT,Judith AB,et al. Oxidized LDL mediates the release of fibroblast growth factor-1. Artherioscler Thromb Vasc Bilo,1997,17:445.
[12]Hiroyuki Y,Shin-Ichi M,Masaaki S,et al. In Vitro Growth Suppression of VSMCs,Using Adenovirus-Mediated Gene Transfer of a Truncated Form of FGF Receptor. Atherosclerosis, 1998,141(1):125.
[13]OKrizanova,J Orlicky.Cs Masanova,et al. Ang I Modulates Catransport Systems in the rat Heart Through Ang Ⅱ. J Mol Cell Cardiol, 1997,29:1739.
, 百拇医药
[14]Adriane SR, Annette S,Gunter B, et al. Heparin-induced Overexpression of bFGF. bFGF Recepter, and Cell-associated Proteoheparan Sulfate in Cultured Coronary SMCs. Artherioscler Thromb Vasc Biol, 1996,16:1063.
[15]HT Yang, Michael RD,Robert WO.et al. bFGF Increases Collateral Blood Flow in Rats with Femoral Arterial Ligation. Circ Res, 1996,79:62.
[16]EJ Su,Lombardi JW,MJAP Daemen,et al. Mitogenic Effect of Ang Ⅱ on Rat Carotid Arteries and Type Ⅱ or Ⅲ Mesenteric Microvessels but not Type I is Mediated by Endogenous bFGF. Circ Res, 1998,82:321.
, http://www.100md.com
[17]Atsushi O,Hitoshi T,Kiyoshi S,et al. Ang Ⅱ Potentiates Vascular EGF-Induced Angiogenic Activity-in Retinal Microcapilary Endothelial Gells. Circ Res, 1998,82:619.
[18]Gursev SD and Aviv H. Atrial and C-type Natriuretic Peptides Amplify Growth Factor Activity in Primary Aortic SMCs. Cardiovascular Res, 1996,31:37.
[19]Saeid B,Krystyna TK,Juan CM,et al. Role of nitric oxide in the angiogenic response in vitro to bFGF. Circ Res. 1998,82(9):1007.
收稿日期：1999-08-03
修稿日期：1999-11-15, 百拇医药
单位：150001 黑龙江省哈尔滨市，哈尔滨医科大学第一临床医学院心血管研究所
关键词：
中国煤炭工业医学杂志000403 本文较全面深刻地阐述了成纤维细胞生长因子生成、释放机制及其影响因素，以及促进动脉粥样硬化形成和发展，血管生长和重塑，干滑肌细胞迁移和增殖的病理性作用和临床意义。
1成纤维细胞
心脏是由心肌细胞和非心肌细胞(成纤维细胞，平滑肌细胞-SMC和血管内皮细胞-VEC)组成，成纤维细胞约占心脏非心肌细胞的2/3，虽然出生后心肌细胞马上丧失增殖能力，但非心肌细胞仍然增殖，甚至在成人心脏。当心脏暴露于各种压力时.例如血液动力学超负荷、心肌梗死、心肌细胞体积增大时，心脏成纤维细胞数量增加，并产生细胞外基质蛋白，如胶原蛋白和纤维蛋白。基质使心肌细胞之间互相联接，维持心肌细胞排列。心脏成纤维细胞影响心肌细胞生成和功能[1,2]。血管紧张素Ⅱ(AngⅡ)刺激心脏成纤维细胞增殖，导致细胞胶原蛋白基因，纤维蛋白基因和整合素基因表达。在心脏成纤维细胞，AngⅡ通过G蛋白的Gby亚单位和酪氨酸激酶激活信号调节激酶。当10-6mol/LAngⅡ加人新生鼠的心脏成纤细胞培养基中，胸腺嘧啶脱氧核苷进入细胞增加40%，这种AngⅡ诱导的增加可被AT1受体拮抗剂(CV-11974)抑制，但不能被AT2受体拮抗剂(PD-123319)抑制[1]。
, http://www.100md.com
酪氨酸激酶和信号调节激酶在AngⅡ诱导的心脏成纤维细胞DNA合成中起关键作用。当心脏暴露于各种损伤时，例如：心肌梗死、心肌炎和心肌肥厚等，心脏成纤维细胞增加细胞外基质蛋白(ECM)的生成。AngⅡ通过AT1受体激活心脏成纤维细胞酪氨酸激酶并增加其DNA合成[1,3]。
在组织修复部位，心肌成纤维细胞对胶原蛋白聚集起主要作用。有人认为：细胞内游离钙增加也与成纤维细胞增殖有关[4,5]。
2成纤维细胞生长因子(FGF)(全文详见PDF)……
参考文献：
[1]Yunzeng Z,Issei K,Jsutomu Y.et al. Cell-Type-Specific Ang II Evoked Signal Transduction Pathways. Circ Res. 1998,82:337.
, 百拇医药
[2]Jingsheng Z,Lydia ON,Xilin L,et al. Stimulation of P2Y receptors Activates c-fos Gene Expression and inhibits DNA Synthesis in Cultured Cardiac Fibroblasts. Cardiovascular Research. 1998,37:718.
[3]Marti CK,Jos FMS,Jan WA.et al. AT2 Receptor Blockade Reduces Cardiac Interstitial Cell DNA Synthesis and Cardiac Function after Rat Myocardial Infarction. J Mol Cell Cardiol, 1998,30:425.
[4]J Geoffrey P,Carol MF,Bao T,et al. Coordinated Effects of Fibroblast geowth Factor-2 on Expression of Fibrillar Collagens. Matrix Metalloproteinases and Tissue Inhibitors of Matrix Metalloproteinases by Human VSMCs. Artherioscler Thromb Vasc Biol, 1997,17(3):475.
, 百拇医药
[5]Felix JAR,Yao S and Karl TW. Myocardial Fibrosis Associated with Aldosterone or Ang II Administration:Attenuation by Calcium Channel Blockade. J Mol Cell Cardiol, 1983,30:475.
[6]George CC,William HB,David SG,et al. Mechanical Strain Ti ghtly Controls FGF-2 Release from Cultured Human VSMCs. Circ Res,1997,80:28.
[7]Masahiko Y,Shokei K,Yasukatsu I,et al. Differential Activation of Cardiac c-Jun Amino-Ferminal Kinase and Extracellular signal Regulated Kinase in Ang II Mediated Hypertension. Sirc Res, 1998,83(7):752.
, 百拇医药
[8]Patrik H, Wulf DI, lmo EH,et al. Intramyocardial infusion of FGF-1 mimics ischemic preconditioning in pig myocardium. J Mol Cell Cardiol, 1998,30:867.
[9]Bradley WD,Yijing C.Denis GB,et al. FGF-2 Decreases Metabolic Coupling and Stimulates Phosphorylation as well as Masking of Connexin 43 Epitopes in Cardiac Myocytes. Circ Res, 1996,79:647.
[10]Xinkang W,Calvert L and Eliot HO. Osteopontin expression in platelet-derived growth factor-stimulated vascular smooth muscle cells and carotid artery after balloon angioplasty. Artherioscler Thromb Vasc Biol, 1996,16:1365.
, 百拇医药
[11]Natatya MA.Alexey VT,Judith AB,et al. Oxidized LDL mediates the release of fibroblast growth factor-1. Artherioscler Thromb Vasc Bilo,1997,17:445.
[12]Hiroyuki Y,Shin-Ichi M,Masaaki S,et al. In Vitro Growth Suppression of VSMCs,Using Adenovirus-Mediated Gene Transfer of a Truncated Form of FGF Receptor. Atherosclerosis, 1998,141(1):125.
[13]OKrizanova,J Orlicky.Cs Masanova,et al. Ang I Modulates Catransport Systems in the rat Heart Through Ang Ⅱ. J Mol Cell Cardiol, 1997,29:1739.
, 百拇医药
[14]Adriane SR, Annette S,Gunter B, et al. Heparin-induced Overexpression of bFGF. bFGF Recepter, and Cell-associated Proteoheparan Sulfate in Cultured Coronary SMCs. Artherioscler Thromb Vasc Biol, 1996,16:1063.
[15]HT Yang, Michael RD,Robert WO.et al. bFGF Increases Collateral Blood Flow in Rats with Femoral Arterial Ligation. Circ Res, 1996,79:62.
[16]EJ Su,Lombardi JW,MJAP Daemen,et al. Mitogenic Effect of Ang Ⅱ on Rat Carotid Arteries and Type Ⅱ or Ⅲ Mesenteric Microvessels but not Type I is Mediated by Endogenous bFGF. Circ Res, 1998,82:321.
, http://www.100md.com
[17]Atsushi O,Hitoshi T,Kiyoshi S,et al. Ang Ⅱ Potentiates Vascular EGF-Induced Angiogenic Activity-in Retinal Microcapilary Endothelial Gells. Circ Res, 1998,82:619.
[18]Gursev SD and Aviv H. Atrial and C-type Natriuretic Peptides Amplify Growth Factor Activity in Primary Aortic SMCs. Cardiovascular Res, 1996,31:37.
[19]Saeid B,Krystyna TK,Juan CM,et al. Role of nitric oxide in the angiogenic response in vitro to bFGF. Circ Res. 1998,82(9):1007.
收稿日期：1999-08-03
修稿日期：1999-11-15, 百拇医药