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cardiovascular RNA decay

Martyna O Urbanek, Wlodzimierz J Krzyzosiak
DNA mutations of various types often affect the cellular localization and function of gene products. The role of mutant transcripts in the pathogenesis of human disease is increasingly recognized. Among the pathogenic RNA variants are transcripts with single nucleotide substitutions, small insertions or deletions, aberrantly or alternatively spliced transcripts and RNAs derived from fused genes. To discriminate among transcripts, particularly those of low abundance, showing small or large sequence differences, a highly sensitive and specific RNA imaging method is required...
July 2017: Mutation Research
Renfang Mao, Riyun Yang, Xia Chen, Edward W Harhaj, Xiaoying Wang, Yihui Fan
RNA-binding proteins (RBPs) are central players in post-transcriptional regulation and immune homeostasis. The ribonuclease and RBP Regnase-1 exerts critical roles in both immune cells and non-immune cells. Its expression is rapidly induced under diverse conditions including microbial infections, treatment with inflammatory cytokines and chemical or mechanical stimulation. Regnase-1 activation is transient and is subject to negative feedback mechanisms including proteasome-mediated degradation or mucosa-associated lymphoid tissue 1 (MALT1) mediated cleavage...
May 2017: Cellular & Molecular Immunology
Marisa W Medina, Frederick Bauzon, Devesh Naidoo, Elizabeth Theusch, Kristen Stevens, Jessica Schilde, Christian Schubert, Lara M Mangravite, Lawrence L Rudel, Ryan E Temel, Heiko Runz, Ronald M Krauss
OBJECTIVE: Interindividual variation in pathways affecting cellular cholesterol metabolism can influence levels of plasma cholesterol, a well-established risk factor for cardiovascular disease. Inherent variation among immortalized lymphoblastoid cell lines from different donors can be leveraged to discover novel genes that modulate cellular cholesterol metabolism. The objective of this study was to identify novel genes that regulate cholesterol metabolism by testing for evidence of correlated gene expression with cellular levels of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) mRNA, a marker for cellular cholesterol homeostasis, in a large panel of lymphoblastoid cell lines...
September 2014: Arteriosclerosis, Thrombosis, and Vascular Biology
Daniel Mapleson, Simon Moxon, Tamas Dalmay, Vincent Moulton
MicroRNAs (miRNAs) are a class of small non-coding RNA (sRNA) involved in gene regulation through mRNA decay and translational repression. In animals, miRNAs have crucial regulatory functions during embryonic development and they have also been implicated in several diseases such as cancer, cardiovascular and neurodegenerative disorders. As such, it is of importance to successfully characterize new miRNAs in order to further study their function. Recent advances in sequencing technologies have made it possible to capture a high-resolution snapshot of the complete sRNA content of an organism or tissue...
January 2013: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
F C Howarth, M A Qureshi, Z Hassan, D Isaev, K Parekh, A John, M Oz, H Raza, E Adeghate, T E Adrian
There has been a spectacular rise in the global prevalence of type 2 diabetes mellitus and cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. The objective of the study was to investigate ventricular myocyte shortening, intracellular Ca(2+) signalling and expression of genes encoding cardiac muscle proteins in the aged Zucker diabetic fatty (ZDF) rat. There was a fourfold elevation in non-fasting blood glucose in ZDF rats (478.43 ± 29.22 mg/dl) compared to controls (108...
February 2012: Molecular and Cellular Biochemistry
Matías Alvarez-Saavedra, Ghadi Antoun, Akiko Yanagiya, Reynaldo Oliva-Hernandez, Daniel Cornejo-Palma, Carolina Perez-Iratxeta, Nahum Sonenberg, Hai-Ying M Cheng
Mammalian circadian rhythms are synchronized to the external time by daily resetting of the suprachiasmatic nucleus (SCN) in response to light. As the master circadian pacemaker, the SCN coordinates the timing of diverse cellular oscillators in multiple tissues. Aberrant regulation of clock timing is linked to numerous human conditions, including cancer, cardiovascular disease, obesity, various neurological disorders and the hereditary disorder familial advanced sleep phase syndrome. Additionally, mechanisms that underlie clock resetting factor into the sleep and physiological disturbances experienced by night-shift workers and travelers with jet lag...
February 15, 2011: Human Molecular Genetics
Kwong-Man Ng, Yee-Ki Lee, Yau-Chi Chan, Wing-Hon Lai, Man-Lung Fung, Ronald A Li, Chung-Wah Siu, Hung-Fat Tse
Hypoxia plays an important role in the proliferation, differentiation and maintenance of the cardiovascular system during development. While low oxygen tension appears to direct the cultured embryonic stem cells (ESCs) to differentiate into cardiomyocytes, the underlying molecular mechanism remains unclear. At a molecular level, hypoxia inducible factor-1 (HIF-1) plays an important role in handling the hypoxia signal. In the present study, we demonstrated that expression of exogenous HIF-1 alpha cDNA into murine ESCs significantly promoted cardiogenesis as indicated by a higher percentage of beating embryoid body and troponin-T positive cell counts as well as increased expression of early and late cardiac markers, such as GATA-binding protein 4 and 6, NK2 transcription factor related locus 5, alpha-myosin heavy chain, beta-myosin heavy chain and myosin light chain 2 ventricular transcripts...
June 2010: Journal of Molecular and Cellular Cardiology
F Cossarini, A Castagna, Adriano Lazzarin
Raltegravir is the first integrase inhibitor approved for the treatment of HIV infection based on the superior efficacy it showed compared to optimized backbone therapy alone in patients harboring multidrug resistant viruses. Studies on naive patients showed comparable efficacy of raltegravir and efavirenz and just recently the US Food and Drug Administration (FDA) approved raltegravir for the use in naive patients based on the favorable results of the international double-blind phase III STARTMRK trial. Additional interesting findings were the faster, and not yet explained, decay of HIV-1 RNA and the higher CD4+ cells increase in the raltegravir group as compared to the efavirenz group...
November 24, 2009: European Journal of Medical Research
Lucia Micale, Maria Giuseppina Turturo, Carmela Fusco, Bartolomeo Augello, Luis A Pérez Jurado, Claudia Izzi, Maria Cristina Digilio, Donatella Milani, Elisabetta Lapi, Leopoldo Zelante, Giuseppe Merla
Supravalvular aortic stenosis (SVAS) is a congenital narrowing of the ascending aorta, which can occur sporadically as an autosomal dominant condition or as one component of the Williams-Beuren syndrome, a complex developmental genomic disorder associated with cardiovascular, neurobehavioral, craniofacial, and metabolic abnormalities, caused by a microdeletion at 7q11.23. We report the identification of seven novel mutations within the elastin gene in 31 familial and sporadic cases of nonsyndromic SVAS. Five are frameshift mutations within the coding region of the ELN gene that result in premature stop codons (PTCs); the other two mutations abolish the donor splice site of introns 3 and 28, respectively, and are predicted to alter splicing efficiency resulting in the generation of a PTC within the same introns of the gene...
March 2010: European Journal of Human Genetics: EJHG
Lucie Carrier, Saskia Schlossarek, Monte S Willis, Thomas Eschenhagen
Cardiomyopathies represent an important cause of cardiovascular morbidity and mortality due to heart failure, arrhythmias, and sudden death. Most forms of hypertrophic cardiomyopathy (HCM) are familial with an autosomal-dominant mode of inheritance. Over the last 20 years, the genetic basis of the disease has been largely unravelled. HCM is considered as a sarcomeropathy involving mutations in sarcomeric proteins, most often beta-myosin heavy chain and cardiac myosin-binding protein C. 'Missense' mutations, more common in the former, are associated with dysfunctional proteins stably integrated into the sarcomere...
January 15, 2010: Cardiovascular Research
Victor A Maltsev, John W Kyle, Sudhish Mishra, Abertas Undrovinas
Late Na(+) current (I(NaL)) is a major component of the action potential plateau in human and canine myocardium. Since I(NaL) is increased in heart failure and ischemia, it represents a novel potential target for cardioprotection. However, the molecular identity of I(NaL) remains unclear. We tested the hypothesis that the cardiac Na(+) channel isoform (Na(v)1.5) is a major contributor to I(NaL) in adult dog ventricular cardiomyocytes (VCs). Cultured VCs were exposed to an antisense morpholino-based oligonucleotide (Na(v)1...
August 2008: American Journal of Physiology. Heart and Circulatory Physiology
Anja Bye, Sveinung Sørhaug, Marcello Ceci, Morten A Høydal, Tomas Stølen, Garrett Heinrich, Arnt E Tjønna, Sonia M Najjar, Odd G Nilsen, Daniele Catalucci, Serena Grimaldi, Riccardo Contu, Sigurd Steinshamn, Gianluigi Condorelli, Godfrey L Smith, Oyvind Ellingsen, Helge Waldum, Ulrik Wisløff
Cigarette smoke contains hundreds of potentially toxic compounds and is an important risk factor for cardiovascular disease. However, the key components responsible for endothelial and myocardial dysfunction have not been fully identified. The objective of the present study was to determine the cardiovascular effects of long-term inhalation of carbon monoxide (CO) administrated to give concentrations in the blood similar to those observed in heavy smokers. Female rats were exposed to either CO or air (control group) (n = 12)...
May 2008: Inhalation Toxicology
Wolfgang Eberhardt, Anke Doller, El-Sayed Akool, Josef Pfeilschifter
During the last decade evidence has accumulated that modulation of mRNA stability plays a central role in cellular homeostasis, including cell differentiation, proliferation and adaptation to external stimuli. The functional relevance of posttranscriptional gene regulation is highlighted by many pathologies, wherein occurrence tightly correlates with a dysregulation in mRNA stability, including chronic inflammation, cardiovascular diseases and cancer. Most commonly, the cis-regulatory elements of mRNA decay are represented by the adenylate- and uridylate (AU)-rich elements (ARE) which are specifically bound by trans-acting RNA binding proteins, which finally determine whether mRNA decay is delayed or facilitated...
April 2007: Pharmacology & Therapeutics
Shumei Zhong, Chichi Liu, David Haviland, Peter A Doris, Ba-Bie Teng
Cardiovascular diseases are often accompanied by elevated LDL particles and endothelial dysfunction. We have examined the possibility of concurrently reducing LDL levels and modulating endothelial function using a single helper-dependent adenovirus vector system to simultaneously express the apolipoprotein B mRNA editing enzyme (Apobec1) and the scavenger receptor, class B, type I (SR-BI) genes under the control of separate promoters (designated HD-C2). Apobec1 edits apoB mRNA at nucleotide C-6666 to produce truncated apoB48 and is normally expressed in small intestine only...
February 2006: Atherosclerosis
Per Reidar Woldbaek, Jørn Bodvar Sande, Taevje Andreas Strømme, Per Kristian Lunde, Srdjan Djurovic, Torstein Lyberg, Geir Christensen, Theis Tønnessen
Although increased levels of circulating interleukin (IL)-18 have been demonstrated in patients with cardiovascular diseases, the functional consequences of chronically increased circulating IL-18 with respect to myocardial function have not been defined. Thus we aimed to examine the effects of chronic IL-18 exposure on left ventricular (LV) function in healthy mice. Moreover, to clarify whether IL-18 has direct effects on the cardiomyocyte, we examined effects of IL-18 on cardiomyocytes in vitro. After 7 days of daily intraperitoneal injections of 0...
August 2005: American Journal of Physiology. Heart and Circulatory Physiology
Wadie F Bahou, Dmitri V Gnatenko
Human blood platelets are intimately involved in the regulation of thrombosis, inflammation, and wound repair. These cells retain megakaryocyte-derived cytoplasmic mRNA and functionally intact protein translational capabilities, although very little is known about normal or pathological mRNA profiles. Microarray analysis has demonstrated a clear and reproducible molecular signature unique to platelets. There is a relative paucity of expressed transcripts compared with those found in other eukaryotic cells, most likely related to mRNA decay in these anucleate cells...
August 2004: Seminars in Thrombosis and Hemostasis
Georg Nickenig, Frank Michaelsen, Cornelius Müller, Anja Berger, Thomas Vogel, Agapios Sachinidis, Hans Vetter, Michael Böhm
AT(1) receptor activation leads to vasoconstriction, blood pressure increase, free radical release, and cell growth. AT(1) receptor regulation contributes to the adaptation of the renin-angiotensin system to long-term stimulation and serves as explanation for the involvement of the AT(1) receptor in the pathogenesis of cardiovascular disease. The molecular mechanisms involved in AT(1) receptor regulation are poorly understood. Here, we report that angiotensin II accelerates AT(1) receptor mRNA decay in vascular smooth muscle cells...
January 11, 2002: Circulation Research
A K Kiemer, A M Vollmar
Atrial natriuretic peptide (ANP), a cardiovascular hormone, has been shown to inhibit synthesis of nitric oxide in lipopolysaccharide (LPS)-activated mouse bone marrow-derived macrophages via activation of its guanylate cyclase-coupled receptor. The goal of the present study was to elucidate the potential sites of inducible nitric-oxide synthase (iNOS) regulation affected by ANP and revealed the following. 1) ANP and dibutyryl-cGMP did not inhibit catalytic iNOS activity measured by the conversion rate of L-[3H]arginine to L-[3H]citrulline in homogenates of LPS-treated cells...
May 29, 1998: Journal of Biological Chemistry
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