Lijnen Paul J, Petrov Victor V, Fagard Robert H
Hypertension and Cardiovascular Rehabilitation Unit, Department of Molecular and Cardiovascular Research, University of Leuven, Leuven, Belgium.
Am J Hypertens. 2003 Jul;16(7):604-11. doi: 10.1016/s0895-7061(03)00847-1.
Discordant findings are reported on the left ventricular transforming growth factor-beta(1) (TGF-beta(1)) mRNA levels in various rat models. Left ventricular TGF-beta(1) mRNA levels did not differ between spontaneously hypertensive rats (SHR) and normal rats, between deoxycorticosterone (DOCA)-salt and sham-operated hypertensive rats, but were increased in stroke-prone spontaneously hypertensive rats (SHRSP) and in post-myocardial infarction (MI) rats. Renal cortical TGF-beta(1) mRNA levels were, however, higher in DOCA-salt hypertensive rats. Angiotensin II subtype 1 receptor antagonism (AT(1)R) and angiotensin converting enzyme inhibition (ACEI) decreased left ventricular and vascular smooth muscle TGF-beta(1) mRNA levels in SHR and renal TGF-beta(1) mRNA in DOCA-salt hypertensive rats and in SHRSP. In post-MI rats ventricular TGF-beta(1) mRNA decreased by AT(1)R antagonism. In essential hypertensive patients, TGF-beta(1) protein as well as TGF-beta(1) mRNA levels are hyperexpressed. The TGF-beta(1) overproduction in hypertension can be attributed to various factors such as elevated angiotensin II, increased systemic blood pressure (BP) per se, increased fluid shear stress and a differential expression of TGF-beta(1) linked to DNA polymorphism in the promoter. The Arg(25) polymorphism in the TGF-beta(1) gene is associated with higher BP. A higher plasma TGF-beta(1) concentration is found in hypertensive patients with microalbuminuria and left ventricle hypertrophy. In these patients, AT(1)R antagonism and ACEI reduced these plasma TGF-beta(1) levels significantly.
在各种大鼠模型中，关于左心室转化生长因子-β1（TGF-β1）mRNA水平的研究结果存在差异。自发性高血压大鼠（SHR）与正常大鼠之间、脱氧皮质酮（DOCA）-盐处理的高血压大鼠与假手术高血压大鼠之间，左心室TGF-β1 mRNA水平没有差异，但在易卒中型自发性高血压大鼠（SHRSP）和心肌梗死后（MI）大鼠中升高。然而，DOCA-盐处理的高血压大鼠肾皮质TGF-β1 mRNA水平较高。血管紧张素II 1型受体拮抗剂（AT1R）和血管紧张素转换酶抑制剂（ACEI）可降低SHR左心室和血管平滑肌TGF-β1 mRNA水平，以及DOCA-盐处理的高血压大鼠和SHRSP的肾TGF-β1 mRNA水平。在MI后大鼠中，AT1R拮抗剂可降低心室TGF-β1 mRNA水平。在原发性高血压患者中，TGF-β1蛋白以及TGF-β1 mRNA水平均过度表达。高血压中TGF-β1的过度产生可归因于多种因素，如血管紧张素II升高、全身血压（BP）本身升高、流体剪切应力增加以及与启动子中DNA多态性相关的TGF-β1差异表达。TGF-β1基因中的Arg(25)多态性与较高的血压相关。在患有微量白蛋白尿和左心室肥厚的高血压患者中发现血浆TGF-β1浓度较高。在这些患者中，AT1R拮抗剂和ACEI可显著降低这些血浆TGF-β1水平。
