Philip-Couderc Pierre, Smih Fatima, Pelat Michel, Vidal Cyril, Verwaerde Patrick, Pathak Atul, Buys Sophie, Galinier Michel, Senard Jean-Michel, Rouet Philippe
INSERM U586, Faculté de Médecine, Laboratoire de Pharmacologie Médicale et Clinique, 37 Allées Jules Guesde. 31073 Toulouse Cedex. France.
Hypertension. 2003 Mar;41(3):414-21. doi: 10.1161/01.HYP.0000057573.32425.95. Epub 2003 Feb 24.
Obesity is associated with volumetric arterial hypertension and with early increase in heart rate and decreased heart rate variability. The consequences of obesity-related hypertension on heart gene regulation are poorly known and were investigated in a model of obesity-related hypertension induced by high fat diet in dogs. When compared with control animals (n=6), a 9-week high fat diet (n=6) provoked significant weight gain and increased blood pressure load and heart rate but failed to significantly change left ventricular mass assessed by echocardiography. Subtractive hybridization of dog heart cDNA libraries were used to generate sublibraries containing differentially expressed cDNAs that were in turn spotted onto membranes to create custom microarrays. Hybridizations of these microarrays with complex probes representing mRNAs expressed in right atria and left ventricles from obese hypertensive and control dogs were performed. Thirty-eight differentially expressed genes were identified; altered expression was confirmed by Northern blot analysis in 15. In addition, real-time quantitative polymerase chain reaction confirmed differential expression for 80% of the randomly chosen tested genes. Once identified, transcripts were categorized into groups involved in metabolism, cell signaling, ionic regulation, cell proliferation, protein synthesis, and tissue remodeling. In addition, we found a set of 11 cDNAs encoding proteins with unknown functions. This study clearly shows that obesity-related hypertension, lasting for only 9 weeks, causes marked changes in gene expression in right atrium as well as the left ventricle that may contribute to early functional changes in heart function and to long-term structural changes such as left ventricular hypertrophy and remodeling.
肥胖与容量性动脉高血压相关，且与心率早期增加及心率变异性降低有关。肥胖相关高血压对心脏基因调控的影响鲜为人知，我们在高脂饮食诱导的犬肥胖相关高血压模型中对此进行了研究。与对照动物（n = 6）相比，9周的高脂饮食（n = 6）导致体重显著增加、血压负荷和心率升高，但通过超声心动图评估发现左心室质量未发生显著变化。利用犬心脏cDNA文库的消减杂交技术构建了包含差异表达cDNA的亚文库，这些亚文库随后被点样到膜上以制作定制微阵列。用代表肥胖高血压犬和对照犬右心房及左心室中表达的mRNA的复杂探针与这些微阵列进行杂交。共鉴定出38个差异表达基因；其中15个基因的表达变化通过Northern印迹分析得到证实。此外，实时定量聚合酶链反应证实了80%随机选择的测试基因存在差异表达。一旦鉴定出来，转录本被分类为参与代谢、细胞信号传导、离子调节、细胞增殖、蛋白质合成和组织重塑的组。此外，我们还发现了一组11个编码功能未知蛋白质的cDNA。这项研究清楚地表明，仅持续9周的肥胖相关高血压会导致右心房和左心室基因表达发生显著变化，这可能有助于心脏功能的早期功能改变以及左心室肥大和重塑等长期结构变化。
