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Molecular markers and mechanisms of stroke: RNA studies

Christopher Cox, Frank R Sharp
Stroke is a leading cause of death and disability, and considerable effort is being expended to investigation of its pathological mechanisms, as well as the identification of clinically relevant biomarkers that could assist in diagnosis. RNA-based analysis of gene expression in blood represents a new field of study addressing both paradigms. A number of recent animal and human studies using microarray technology demonstrate rapidly-induced, measurable changes in gene expression in response to ischemic trauma, and distinct expression 'profiles' specific to the injury subtype...
June 2013: Neurological Research
Chunmei Wang, Luciana P Schwab, Meiyun Fan, Tiffany N Seagroves, John K Buolamwini
Dipyridamole (DPM) is widely used to prevent strokes and vascular thrombosis. Combination therapy of DPM and antimetabolites has shown synergistic anticancer activity. This study investigated the chemopreventive effects of DPM in the mouse mammary tumor virus promoter-driven polyoma middle T oncoprotein metastatic breast cancer model. We also investigated the effects of DPM on gene and miRNA expression. Chemopreventive activity was assessed by comparing the time to onset of palpable lesions, primary tumor growth kinetics, and the number of lung metastases in transgenic mice treated with DPM or vehicle...
May 2013: Cancer Prevention Research
Silvia Udali, Patrizia Guarini, Sara Moruzzi, Sang-Woon Choi, Simonetta Friso
Epigenetic phenomena are defined as heritable mechanisms that establish and maintain mitotically stable patterns of gene expression without modifying the base sequence of DNA. The major epigenetic features of mammalian cells include DNA methylation, post-translational histone modifications and RNA-based mechanisms including those controlled by small non-coding RNAs (miRNAs). The impact of epigenetic mechanisms in cardiovascular pathophysiology is now emerging as a major player in the interface between genotype to phenotype variability...
July 2013: Molecular Aspects of Medicine
Siri T Lehtonen, Jussi Mäkelä, Steffen Ohlmeier, Kari Ylitalo, Tatu Juvonen, Vesa Anttila, Petri Lehenkari
Although several studies have demonstrated a functional recovery of infarcted myocardial tissue after cell therapy, little is known about the molecular mechanisms behind it. The aim of this study was to characterize the effect of cell therapy at the molecular level to screen for novel target candidates for future therapy of infarcted myocardial tissue. We used a swine acute myocardial infarction model evoked by transient occlusion of the circumflex coronary artery. Autologous bone marrow-derived mononuclear cells (BMMCs) or saline were injected intramyocardially or into the circumflex coronary artery...
February 2014: Journal of Tissue Engineering and Regenerative Medicine
Takashi Moriya, Kazuya Kitamori, Hisao Naito, Yukie Yanagiba, Yuki Ito, Nozomi Yamagishi, Hazuki Tamada, Xiaofang Jia, Satoru Tsuchikura, Katsumi Ikeda, Yukio Yamori, Tamie Nakajima
OBJECTIVES: The aim of this study was to identify the molecular mechanisms underlying high-fat and high-cholesterol (HFC) diet-induced steatohepatitis and associated liver fibrosis progression in a novel stroke-prone, spontaneously hypertensive 5/Dmcr (SHRSP5/Dmcr) rat model. METHODS: SHRSP5/Dmcr rats were given the control or HFC-diet for 2, 8, and 16 weeks. Plasma and hepatic gene expression of key molecules involved in fatty acid oxidation, inflammation, oxidative stress, and fibrosis were subsequently analyzed...
November 2012: Environmental Health and Preventive Medicine
Frank R Sharp, Glen C Jickling, Boryana Stamova, Yingfang Tian, Xinhua Zhan, DaZhi Liu, Beth Kuczynski, Christopher D Cox, Bradley P Ander
Whole genome expression microarrays can be used to study gene expression in blood, which comes in part from leukocytes, immature platelets, and red blood cells. Since these cells are important in the pathogenesis of stroke, RNA provides an index of these cellular responses to stroke. Our studies in rats have shown specific gene expression changes 24  hours after ischemic stroke, hemorrhage, status epilepticus, hypoxia, hypoglycemia, global ischemia, and following brief focal ischemia that simulated transient ischemic attacks in humans...
July 2011: Journal of Cerebral Blood Flow and Metabolism
T L Barr, Y Conley, J Ding, A Dillman, S Warach, A Singleton, M Matarin
OBJECTIVE: The objective of this study was to provide insight into the molecular mechanisms of acute ischemic cerebrovascular syndrome (AICS) through gene expression profiling and pathway analysis. METHODS: Peripheral whole blood samples were collected from 39 MRI-diagnosed patients with AICS and 25 nonstroke control subjects ≥ 18 years of age. Total RNA was extracted from whole blood stabilized in Paxgene RNA tubes, amplified, and hybridized to Illumina HumanRef-8v2 bead chips...
September 14, 2010: Neurology
Raghu Vemuganti, Robert J Dempsey
The molecular mechanisms that render a carotid atherosclerotic plaque symptomatic have not yet been identified. Using an Affymetrix Human GeneChip set, we analyzed the gene expression patterns of 44 862 mRNA transcripts in surgically removed carotid artery plaques from six patients with symptomatic stroke and four non-symptomatic patients. The age, body mass index and the degree of stenosis were similar in the two groups. Some 236 transcripts (approximately 0.5% of the total transcripts analyzed) were expressed more abundantly in the symptomatic than the asymptomatic group...
April 2006: Journal of Neurochemistry
R W K Chiu, T H Rainer, Y M D Lo
Much research interest has been shown in recent years for the development of molecular diagnostic strategies based on the analysis of DNA/RNA molecules that are present in the plasma/serum of human subjects. Reported applications include the diagnosis, prognostication or monitoring of malignancies and pregnancy-associated complications. While researchers have speculated that cell death is a potential mechanism that leads to the release of DNA/RNA into the circulation, studies have demonstrated that indeed increased amounts of plasma DNA and RNA could be detected in patients sustaining acute traumatic injuries...
2005: Acta Neurochirurgica. Supplement
Saurabh Chatterjee, Sudha Premachandran, Deepak Sharma, Raghavendra S Bagewadikar, T B Poduval
Heat stroke-induced death is a major killer worldwide. Mice were subjected to acute heat stress by exposing them to whole-body hyperthermia (WBH) treatment and were used as a model to study heat stroke. Administration of L-arginine (L-arg, 120 mg/kg, i.p) 2 h after the cessation of WBH rescued the mice from heat-induced death and reduced the hypothermia. Heat shock protein 70 levels in the liver were increased significantly in heat-stressed mice administered L-arg compared with the heat-stressed group. WBH induced apoptosis, as indicated by DNA fragmentation, and increased levels of p53 and caspase-3 activity, which were significantly reduced by the administration of L-arg...
October 2005: Shock
R Vemuganti, R J Dempsey
Identification of genetic mechanisms that promote the onset of stroke and transient cerebral ischemic attack symptoms in carotid atherosclerotic patients would further our understanding of the pathophysiology of this disease and could lead to new pharmacological and molecular therapies. Using Affymetrix Human Genome 230 GeneChip set, the present study evaluated the gene expression differences in geometrically similar carotid artery plaque samples extricated from six symptomatic stroke patients and four asymptomatic patients...
2005: Neuroscience
Amélie Rodrigue-Way, Daniel Burkhoff, Bard J Geesaman, Serge Golden, Jian Xu, Matthew J Pollman, Mary Donoghue, Raju Jeyaseelan, Steven Houser, Roger E Breitbart, Andrew Marks, Susan Acton
BACKGROUND: Left ventricular assist devices (LVADs) implanted in patients with severe congestive heart failure (CHF) as a bridge to transplantation have been shown to reverse chamber enlargement, regress cellular hypertrophy, and increase contractility. The purpose of this study was to gain a better understanding of the molecular changes associated with increased contractility after LVAD support. METHODS: We took tissue sections from the left ventricular apex of 12 patients with CHF who were undergoing LVAD insertion (pre-LVAD) and from the LV free wall of those same patients before transplantation (post-LVAD)...
January 2005: Journal of Heart and Lung Transplantation
J C Tsai, M A Perrella, M Yoshizumi, C M Hsieh, E Haber, R Schlegel, M E Lee
Plasma homocysteine levels are elevated in 20-30% of all patients with premature atherosclerosis. Although elevated homocysteine levels have been recognized as an independent risk factor for myocardial infarction and stroke, the mechanism by which these elevated levels cause atherosclerosis is unknown. To understand the role of homocysteine in the pathogenesis of atherosclerosis, we examined the effect of homocysteine on the growth of both vascular smooth muscle cells and endothelial cells at concentrations similar to those observed in clinical studies...
July 5, 1994: Proceedings of the National Academy of Sciences of the United States of America
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