Lu Hong, Boustany-Kari Carine M, Daugherty Alan, Cassis Lisa A
Cardiovascular Research Center, Gill Heart Institute, University of Kentucky, Lexington, Kentucky 4053-0200, USA.
Am J Physiol Endocrinol Metab. 2007 May;292(5):E1280-7. doi: 10.1152/ajpendo.00277.2006. Epub 2007 Jan 9.
In addition to the well-defined contribution of the liver, adipose tissue has been recognized as an important source of angiotensinogen (AGT). The purpose of this study was to define the angiotensin II (ANG II) receptors involved in regulation of adipose AGT and the relationship of this control to systemic AGT and/or angiotensin peptide concentrations. In LDL receptor-deficient (LDLR(-/-)) male mice, adipose mRNA abundance of AGT was 68% of that in liver, and adipose mRNA abundance of the angiotensin type 1a (AT(1a)) receptor (AT(1a)R) was 38% of that in liver, whereas mRNA abundance of the angiotensin type 2 (AT(2)) receptor (AT(2)R) was 57% greater in adipose tissue than in liver. AGT and angiotensin peptide concentrations were decreased in plasma of AT(1a)R-deficient (AT(1a)R(-/-)) mice and were paralleled by reductions in AGT expression in liver. In contrast, adipose AGT mRNA abundance was unaltered in AT(1a)R(-/-) mice. AT(2)R(-/-) mice exhibited elevated plasma angiotensin peptide concentrations and marked elevations in adipose AGT and AT(1a)R mRNA abundance. Increases in adipose AGT mRNA abundance in AT(2)R(-/-) mice were abolished by losartan. In contrast, liver AGT and AT(1a)R mRNA abundance were unaltered in AT(2)R(-/-) mice. Infusion of ANG II for 28 days into LDLR(-/-) mice markedly increased adipose AGT and AT(1a)R mRNA but did not alter liver AGT and AT(1a)R mRNA. These results demonstrate that differential mRNA abundance of AT(1a)/AT(2) receptors in adipose tissue vs. liver contributes to tissue-specific ANG II-mediated regulation of AGT. Chronic infusion of ANG II robustly stimulated AT(1a)R and AGT mRNA abundance in adipose tissue, suggesting that adipose tissue serves as a primary contributor to the activated systemic renin-angiotensin system.
除了肝脏已明确的作用外，脂肪组织也被认为是血管紧张素原（AGT）的重要来源。本研究的目的是确定参与调节脂肪AGT的血管紧张素II（ANG II）受体，以及这种调控与全身AGT和/或血管紧张素肽浓度之间的关系。在低密度脂蛋白受体缺陷（LDLR(-/-)）雄性小鼠中，脂肪组织中AGT的mRNA丰度是肝脏中的68%，血管紧张素1a（AT(1a)）受体（AT(1a)R）的脂肪mRNA丰度是肝脏中的38%，而血管紧张素2（AT(2)）受体（AT(2)R）的mRNA丰度在脂肪组织中比肝脏中高57%。AT(1a)R缺陷（AT(1a)R(-/-)）小鼠血浆中的AGT和血管紧张素肽浓度降低，同时肝脏中AGT表达也降低。相反，AT(1a)R(-/-)小鼠脂肪组织中AGT的mRNA丰度未改变。AT(2)R(-/-)小鼠血浆血管紧张素肽浓度升高，脂肪组织中AGT和AT(1a)R的mRNA丰度显著升高。氯沙坦可消除AT(2)R(-/-)小鼠脂肪组织中AGT的mRNA丰度增加。相反，AT(2)R(-/-)小鼠肝脏中AGT和AT(1a)R的mRNA丰度未改变。向LDLR(-/-)小鼠输注ANG II 28天可显著增加脂肪组织中AGT和AT(1a)R的mRNA，但不改变肝脏中AGT和AT(1a)R的mRNA。这些结果表明，脂肪组织与肝脏中AT(1a)/AT(2)受体的mRNA丰度差异导致了ANG II介导的AGT的组织特异性调控。长期输注ANG II可强烈刺激脂肪组织中AT(1a)R和AGT的mRNA丰度，提示脂肪组织是激活的全身肾素-血管紧张素系统的主要贡献者。
