Analysis of genes causing hypertension and stroke in spontaneously hypertensive rats: Gene expression profiles in the brain

Abstract

Abstract. Spontaneously hypertensive rats (SHR) and strokeprone SHR (SHRSP) are frequently used as rat models not only of essential hypertension and stroke, but also of attention-deficit hyperactivity disorder (ADHD). Normotensive Wistar-Kyoto rats (WKY) are used as the control rats in these cases. An increasing number of studies has demonstrated the critical role of the central nervous system in the development and maintenance of hypertension. In a previous study, we analyzed the gene expression profiles in the adrenal glands of SHR. Thus, in this study, we analyzed gene expression profiles in the brains of SHR in order to identify the genes responsible for causing hypertension and stroke, as well as those involved in ADHD. Using genome-wide microarray technology, we examined the gene expression profiles in the brains of 3 rat strains (SHR, SHRSP and WKY) when the rats were 3 and 6 weeks of age, a period in which the rats are considered to be in a prehypertensive state. Gene expression profiles in the brain were compared between SHR and WKY, and between SHRSP and SHR. A total of 179 genes showing a >4-or <-4-fold change in expression were isolated, and candidate genes were selected using two different web tools: the first tool was the Database for Annotation, Visualization and Integrated Discovery (DAVID), which was used to search for significantly enriched genes, and categorized them using Gene Ontology (GO) terms, and the second was the network explorer of Ingenuity Pathway Analysis (IPA), which was used to search for interaction networks among SHR-and SHRSP-specific genes. The IPA of SHR-specific genes revealed that prostaglandin E receptor 4 (Ptger4) is one of the candidate genes responsible for causing hypertension in SHR, and that albumin (Alb) and chymase 1 (Cma1) are also responsible for causing hypertension in SHR in the presence of angiotensinogen (Agt). Similar analyses of SHRSP-specific genes revealed that the angiotensin II receptorassociated gene (Agtrap) interacts with the FBJ osteosarcoma oncogene (Fos), and with the angiotensin II receptor type-1b (Agtr1b). As Agtrap and Agtr1b not only participate in the 'uptake of norepinephrine' and 'blood pressure', but also in the 'behavior' of SHRSP at 6 weeks of age, our data demonstrate a close association between hypertension and ADHD.

Microarray expression profiles of genes in lung tissues of rats subjected to focal cerebral ischemia-induced lung injury following bone marrow-derived mesenchymal stem cell transplantation

“…Gene chip technology and data analysis has been successfully applied in many fields, such as clinical diagnosis, medication guide, drug screening (40), as well as basic medicine (41,42) (expression profiling studies, gene mutation studies and gene component type and sequencing). Gene chip technology is able to analyze a high content of information, in a high-throughput manner, and is rapid and accurate (42).…”

“…Gene chip technology and data analysis has been successfully applied in many fields, such as clinical diagnosis, medication guide, drug screening (40), as well as basic medicine (41,42) (expression profiling studies, gene mutation studies and gene component type and sequencing). Gene chip technology is able to analyze a high content of information, in a high-throughput manner, and is rapid and accurate (42). In addition, microarray and bioinformatics are complementary to Gene chip technology that were developed to be able to rapidly obtain large amounts of genetic information; they can provide the necessary database for bioinformatics research, while data analysis of gene chips also greatly depends on bioinformatics.…”

MicroRNA network changes in the brain stem underlie the development of hypertension

“…We focused on potential target genes that are involved processes with known functional impact on development and maintenance of hypertension. We developed a list of 144 potential target transcripts that are associated with AT1R signaling through Pkc, CamkII, Mapk, and Pi3k pathways, immediate early genes (e.g., Fos, Egr1, Egr2, Egr3, Jun, Junb), and ion channels and transporters, guided by our previous studies (27,34,39,40,42,51,53,54), as well as genes relevant to inflammatory pathways shown to affect blood pressure regulation, including interleukins, chemokines, and leukotrienes (19,52,60). Several of these pathways are enriched in astrocytes (e.g., inflammatory processes) compared with neurons (e.g., ion channels) compared with endothelial cells (e.g., junctional proteins), whereas the transcriptional regulators and signaling pathways may be common to all cell types (38).…”

Effects of brain renin- angiotensin system inhibition in ISIAH rats with inherited stress-induced arterial hypertension

“…Что касается ингибирования АСЕ, которое не привело к снижению АД, то этот результат может быть связан с развитыми компенсаторными реакциями, возникающими в ответ на ингибирование ACE у крыс НИСАГ, а именно с активацией АСЕ-независимых механизмов генерации Ang II. К таковым можно отнести конверсию Ang I в Ang II химазой, обнаруженной в тканях мозга многих млекопитающих, в том числе гипертензивных крыс SHR (Yoshida et al, 2014). В результате такого альтернативного пути может генерироваться достаточное количество Ang II для стимуляции рецепторов AT1A и поддержания АД на повышенном у гипертензивных крыс уровне.…”