Forte Amalia, Galderisi Umberto, De Feo Marisa, Quarto Cesare, Renzulli Attilio, Berrino Liberato, Rossi Francesco, Cascino Antonino, Cipollaro Marilena
Department of Experimental Medicine, Excellence Research Centre for Cardiovascular Diseases C.R.I.S.C.E.B., Second University of Naples, Naples, Italy.
Int J Mol Med. 2005 Dec;16(6):1057-64.
Analysis of gene expression profiles in patients or in animal models affected by cardiovascular diseases may provide insight into therapeutic strategies. In this study, 3 rat strains, Wistar Kyoto (WKY), spontaneously hypertensive rats (SHR) and the Milan hypertensive rat strain (MHS), have been investigated to assess the influence of genetic background and/or of hypertension on gene expression in arteriotomy-injured carotid arteries (CAs). Expression profiles of genes, c-myc, AT1, AT2, ETA, ETB, Bcl-2, Bax and Bcl-X, were determined by reverse transcription-polymerase chain reaction (RT-PCR) in the acute phase, from 1 to 48 h, following CA arteriotomy. WKY, SHR and MHS show significant differences in gene expression profiles after CA arteriotomy. c-Myc mRNA is activated earlier and/or to a greater extent in hypertensive strains than in WKY (p<0.05). AT1 mRNA increases in WKY after injury, while it decreases in both SHR and MHS (p<0.05). AT2 shows the opposite behaviour, decreasing in WKY and increasing in hypertensive strains (p<0.05). ETA mRNA decreases in all strains although with different timing and levels, associated with a replacement by ETB mRNA (p<0.05). Bcl-2/Bax ratio gradually decreases in WKY, while it decreases only transiently in SHR and MHS 4 h after injury (p<0.05). Overall data indicate that therapeutic strategies for stenosis prevention should carefully consider the gene expression profile after injury, the genetic background, the kind of vascular trauma and the diseases affecting the animal model or the patient.
对患有心血管疾病的患者或动物模型的基因表达谱进行分析，可能有助于深入了解治疗策略。在本研究中，研究了3种大鼠品系，即Wistar Kyoto（WKY）大鼠、自发性高血压大鼠（SHR）和米兰高血压大鼠品系（MHS），以评估遗传背景和/或高血压对颈动脉切开术损伤的颈动脉（CA）中基因表达的影响。通过逆转录聚合酶链反应（RT-PCR）在CA动脉切开术后1至48小时的急性期测定c-myc、AT1、AT2、ETA、ETB、Bcl-2、Bax和Bcl-X等基因的表达谱。WKY、SHR和MHS在CA动脉切开术后的基因表达谱存在显著差异。与WKY相比，高血压品系中的c-Myc mRNA激活更早和/或程度更大（p<0.05）。损伤后WKY中的AT1 mRNA增加，而SHR和MHS中的AT1 mRNA均减少（p<0.05）。AT2表现出相反的行为，在WKY中减少，在高血压品系中增加（p<0.05）。所有品系中的ETA mRNA均减少，尽管时间和水平不同，同时伴有ETB mRNA的替代（p<0.05）。WKY中的Bcl-2/Bax比值逐渐降低，而SHR和MHS在损伤后4小时仅短暂降低（p<0.05）。总体数据表明，预防狭窄的治疗策略应仔细考虑损伤后的基因表达谱、遗传背景、血管创伤类型以及影响动物模型或患者的疾病。
