Epidermal growth factor-like domain-containing protein 7 (EGFL7) is upregulated in human epithelial tumors and so is a potential biomarker for malignancy. Indeed, previous studies have shown that high EGFL7 expression promotes infiltration and metastasis of gastric carcinoma. The epithelial–mesenchymal transition (EMT) initiates the metastatic cascade and endows cancer cells with invasive and migratory capacity; however, it is not known if EGFL7 promotes metastasis by triggering EMT. We found that EGFL7 was overexpressed in multiple human gastric cancer (GC) cell lines and that overexpression promoted cell invasion and migration as revealed by scratch wound and transwell migration assays. Conversely, shRNA-mediated EGFL7 knockdown reduced invasion and migration. Furthermore, EGFL7-overexpressing cells grew into larger tumors and were more likely to metastasize to the liver compared to underexpressing CG cells following subcutaneous injection in mice. EGFL7 overexpression protected GC cell lines against anoikis, providing a plausible mechanism for this enhanced metastatic capacity. In excised human gastric tumors, expression of EGFL7 was positively correlated with expression levels of the mesenchymal marker vimentin and the EMT-associated transcription repressor Snail, and negatively correlated with expression of the epithelial cell marker E-cadherin. In GC cell lines, EGFL7 knockdown reversed morphological signs of EMT and decreased both vimentin and Snail expression. In addition, EGFL7 overexpression promoted EGF receptor (EGFR) and protein kinase B (AKT) phospho-activation, effects markedly suppressed by the EGFR tyrosine kinase inhibitor AG1478. Moreover, AG1478 also reduced the elevated invasive and migratory capacity of GC cell lines overexpressing EGFL7. Collectively, these results strongly suggest that EGFL7 promotes metastasis by activating EMT through an EGFR−AKT−Snail signaling pathway. Disruption of EGFL7−EGFR−AKT−Snail signaling may a promising therapeutic strategy for gastric cancer.
Trials on sling exercise (SE), commonly performed to manage chronic low back pain (LBP), yield conflicting results. This study aimed to review the effects of SE on chronic LBP.
The randomized controlled trials comparing SE with other treatments or no treatment, published up to August 2013, were identified by electronic searches. Primary outcomes were pain, function, and return to work. The weighted mean difference (WMD) and 95% confidence interval (CI) were calculated, using a random-effects model.
Risk of bias was rated as high in 9 included trials, where some important quality components such as blinding were absent and sample sizes were generally small. We found no clinically relevant differences in pain or function between SE and other forms of exercise, traditional Chinese medical therapy, or in addition to acupuncture. Based on two trials, SE was more effective than thermomagnetic therapy at reducing pain (short-term: WMD –13.90, 95% CI –22.19 to –5.62; long-term: WMD –26.20, 95% CI –31.32 to –21.08) and improving function (short-term: WMD –10.54, 95% CI –14.32 to –6.75; long-term: WMD –25.75, 95% CI –30.79 to –20.71). In one trial we found statistically significant differences between SE and physical agents combined with drug therapy (meloxicam combined with eperisone hydrochloride) but of borderline clinical relevance for pain (short-term: WMD –15.00, 95% CI –19.64 to −10.36) and function (short-term: WMD −10.00; 95% CI −13.70 to −6.30). There was substantial heterogeneity among the two trials comparing SE and thermomagnetic therapy; both these trials and the trial comparing SE with physical agents combined with drug therapy had serious methodological limitations.
Based on limited evidence from 2 trials, SE was more effective for LBP than thermomagnetic therapy. Clinically relevant differences in effects between SE and other forms of exercise, physical agents combined with drug therapy, traditional Chinese medical therapy, or in addition to acupuncture could not be found. More high-quality randomized trials on the topic are warranted.
Although B cells play important roles in the humoral immune response and the regulation of adaptive immunity, B cell subpopulations with unique phenotypes, particularly those with non-classical immune functions, should be further investigated. By challenging mice with Listeria monocytogenes, Escherichia coli, vesicular stomatitis virus and Toll-like receptor ligands, we identified an inducible CD11ahiFcγRIIIhi B cell subpopulation that is significantly expanded and produces high levels of IFN-γ during the early stage of the immune response. This subpopulation of B cells can promote macrophage activation via generating IFN-γ, thereby facilitating the innate immune response against intracellular bacterial infection. As this new subpopulation is of B cell origin and exhibits the phenotypic characteristics of B cells, we designated these cells as IFN-γ-producing innate B cells. Dendritic cells were essential for the inducible generation of these innate B cells from the follicular B cells via CD40L-CD40 ligation. Increased Bruton's tyrosine kinase activation was found to be responsible for the increased activation of non-canonical NF-κB pathway in these innate B cells after CD40 ligation, with the consequent induction of additional IFN-γ production. The identification of this new population of innate B cells may contribute to a better understanding of B cell functions in anti-infection immune responses and immune regulation.
B cells; IFN-γ; innate response; dendritic cells; CD40
Saprotrophy on plant biomass is a recently developed nutrition strategy for Trichoderma. However, the physiology and evolution of this new nutrition strategy is still elusive. We report the deep sequencing and analysis of the genome of Trichoderma longibrachiatum, an efficient cellulase producer. The 31.7-Mb genome, smallest among the sequenced Trichoderma species, encodes fewer nutrition-related genes than saprotrophic T. reesei (Tr), including glycoside hydrolases and nonribosomal peptide synthetase–polyketide synthase. Homology and phylogenetic analyses suggest that a large number of nutrition-related genes, including GH18 chitinases, β-1,3/1,6-glucanases, cellulolytic enzymes, and hemicellulolytic enzymes, were lost in the common ancestor of T. longibrachiatum (Tl) and Tr. dN/dS (ω) calculation indicates that all the nutrition-related genes analyzed are under purifying selection. Cellulolytic enzymes, the key enzymes for saprotrophy on plant biomass, are under stronger purifying selection pressure in Tl and Tr than in mycoparasitic species, suggesting that development of the nutrition strategy of saprotrophy on plant biomass has increased the selection pressure. In addition, aspartic proteases, serine proteases, and metalloproteases are subject to stronger purifying selection pressure in Tl and Tr, suggesting that these enzymes may also play important roles in the nutrition. This study provides insights into the physiology and evolution of the nutrition strategy of Trichoderma.
Trichoderma longibrachiatum; cellulolytic enzymes; carbohydrate-active enzymes; proteases; purifying selection; dN/dS
Pseudoalteromonas species are a group of marine gammaproteobacteria frequently found in deep-sea sediments, which may play important roles in deep-sea sediment ecosystem. Although genome sequence analysis of Pseudoalteromonas has revealed some specific features associated with adaptation to the extreme deep-sea environment, it is still difficult to study how Pseudoalteromonas adapt to the deep-sea environment due to the lack of a genetic manipulation system. The aim of this study is to develop a genetic system in the deep-sea sedimentary bacterium Pseudoalteromonas sp. SM9913, making it possible to perform gene mutation by homologous recombination.
The sensitivity of Pseudoalteromonas sp. SM9913 to antibiotic was investigated and the erythromycin resistance gene was chosen as the selective marker. A shuttle vector pOriT-4Em was constructed and transferred into Pseudoalteromonas sp. SM9913 through intergeneric conjugation with an efficiency of 1.8 × 10-3, which is high enough to perform the gene knockout assay. A suicide vector pMT was constructed using pOriT-4Em as the bone vector and sacB gene as the counterselective marker. The epsT gene encoding the UDP-glucose lipid carrier transferase was selected as the target gene for inactivation by in-frame deletion. The epsT was in-frame deleted using a two-step integration–segregation strategy after transferring the suicide vector pMT into Pseudoalteromonas sp. SM9913. The ΔepsT mutant showed approximately 73% decrease in the yield of exopolysaccharides, indicating that epsT is an important gene involved in the EPS production of SM9913.
A conjugal transfer system was constructed in Pseudoalteromonas sp. SM9913 with a wide temperature range for selection and a high transfer efficiency, which will lay the foundation of genetic manipulation in this strain. The epsT gene of SM9913 was successfully deleted with no selective marker left in the chromosome of the host, which thus make it possible to knock out other genes in the same host. The construction of a gene knockout system for Pseudoalteromonas sp. SM9913 will contribute to the understanding of the molecular mechanism of how Pseudoalteromonas adapt to the deep-sea environment.
Despite an estimated 1 million tobacco-related deaths annually in China, public health officials face overwhelming barriers to implementing effective tobacco control policies and programs. Models of effective tobacco control can be adapted for Chinese tobacco use and culture based on reliable and valid data regarding predictors of smoking and abstaining.
As part of the China Seven Cities Study to assess the role of rapid social, economic, and cultural change on tobacco use and related health practices and outcomes, 4,072 adult male smokers provided data in 3 annual waves. Measures included current smoking, nicotine dependence, readiness for quitting, perceived stress, hostility, depressive symptoms, as well as covariates (e.g., age, marital status, educational attainment, and family income).
Odds of being abstinent at Wave 3 were increased by: lower nicotine dependence at Wave 1 and becoming less dependent between Waves 1 and 3; progressing beyond the contemplation stage between Waves 1 and 3; perceiving less stress, whether initially at Wave 1 or over time from Wave 1 to Wave 3; and lower hostility scores at Wave 1 and decreased hostility from Wave 1 to Wave 3. Among those who quit, odds of remaining abstinent rather than relapsing by Wave 3 were higher among those who were less dependent at Wave 1 and who became less dependent from Wave 1 to Wave 3; and those who showed decreases in hostility from Wave 1 to Wave 3.
The public health challenge posed by very high prevalence of male smoking in China can be met by policies and programs that lead to successful long-term cessation. This can only be done successfully by designing interventions based on knowledge of the country’s smokers and the current study suggests several elements.
Deep sequencing has become a popular tool for novel miRNA detection but its data must be viewed carefully as the state of the field is still undeveloped. Using three different programs, miRDeep (v1, 2), miRanalyzer and DSAP, we have analyzed seven data sets (six biological and one simulated) to provide a critical evaluation of the programs performance. We selected these software based on their popularity and overall approach toward the detection of novel and known miRNAs using deep-sequencing data. The program comparisons suggest that, despite differing stringency levels they all identify a similar set of known and novel predictions. Comparisons between the first and second version of miRDeep suggest that the stringency level of each of these programs may, in fact, be a result of the algorithm used to map the reads to the target. Different stringency levels are likely to affect the number of possible novel candidates for functional verification, causing undue strain on resources and time. With that in mind, we propose that an intersection across multiple programs be taken, especially if considering novel candidates that will be targeted for additional analysis. Using this approach, we identify and performed initial validation of 12 novel predictions in our in-house data with real-time PCR, six of which have been previously unreported.
deep sequencing; software; miRNA detection; comparison
Aberrant promoter methylation is recognized as an important feature of breast carcinogenesis. We hypothesized that genetic variation of genes for methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR), two critical enzymes in one-carbon metabolism, may alter DNA methylation levels, and thus influence DNA methylation in breast cancer. We evaluated case-control association of MTHFR C677T, A1298C, and MTR A2756G polymorphisms for cases strata defined by promoter methylation status for each of three genes, E- cadherin, p16, and RAR-β2 in breast cancer; in addition, we evaluated case-case comparisons of likelihood of promoter methylation in relation to genotypes using a population-based case-control study conducted in Western New York State. Methylation was evaluated with real time methylation-specific PCRs for 803 paraffin embedded breast tumor tissues from women with primary, incident breast cancer. We applied unordered polytomous regression and unconditional logistic regression to derive adjusted odds ratios (OR) and 95% confidence intervals (CI). We did not find any association of MTHFR and MTR polymorphisms with breast cancer risk stratified by methylation status nor between polymorphisms and likelihood of promoter methylation of any of the genes. There was no evidence of difference within strata defined by menopausal status, ER status, folate intake and lifetime alcohol consumption. Overall, we found no evidence that these common polymorphisms of the MTHFR and MTR genes are associated with promoter methylation of E- cadherin, p16, and RAR-β2 genes in breast cancer.
promoter methylation; MTHFR; MTR; breast cancer; epidemiology; genetic polymorphisms
Divergently paired genes (DPGs), also known as bidirectional (head-to-head positioned) genes, are conserved across species and lineages, and thus deemed to be exceptional in genomic organization and functional regulation. Despite previous investigations on the features of their conservation and gene organization, the functional relationship among DPGs in a given species and lineage has not been thoroughly clarified. Here we report a network-based comprehensive analysis on human DPGs and our results indicate that the two members of the DPGs tend to participate in different biological processes while enforcing related functions as modules. Comparing to randomly paired genes as a control, the DPG pairs have a tendency to be clustered in similar “cellular components” and involved in similar “molecular functions”. The functional network bridged by DPGs consists of three major modules. The largest module includes many house-keeping genes involved in core cellular activities. This module also shows low variation in expression in both CNS (central nervous system) and non-CNS tissues. Based on analyses of disease transcriptome data, we further suggest that this particular module may play crucial roles in HIV infection and its disease mechanism.
While the effects of hypoxia on gene expression have been investigated in the CNS to some extent, we currently do not know what role epigenetics plays in the transcription of many genes during such hypoxic stress. To start understanding the role of epigenetic changes during hypoxia, we investigated the long-term effect of hypoxia on gene expression and DNA methylation in hippocampal neuronal cells. Primary murine hippocampal neuronal cells were cultured for 7 days. Hypoxic stress of 1% O2, 5% CO2 for 24 hours was applied on Day 3, conditions we found to maximize cellular hypoxic stress response without inducing cell death. Cells were returned to normoxia for 4 days following the period of hypoxic stress. On Day 7, Methyl-Sensitive Cut Counting (MSCC) was used to identify a genome-wide methylation profile of the hippocampal cell lines to assess methylation changes resulting from hypoxia. RNA-Seq was also done on Day 7 to analyze changes in gene transcription. Phenotypic analysis showed that neuronal processes were significantly shorter after 1 day of hypoxia, but there was a catch-up growth of these processes after return to normoxia. Transcriptome profiling using RNA-Seq revealed 369 differentially expressed genes with 225 being upregulated, many of which form networks shown to affect CNS development and function. Importantly, the expression level of 59 genes could be correlated to the changes in DNA methylation in their promoter regions. CpG islands, in particular, had a strong tendency to remain hypomethylated long after hypoxic stress was removed. From this study, we conclude that short-term, sub-lethal hypoxia results in long-lasting changes to genome wide DNA methylation status and that some of these changes can be highly correlated with transcriptional modulation in a number of genes involved in functional pathways that have been previously implicated in neural growth and development.
Mental disorders account for a substantial proportion of the total disease burden in China but the number, distribution and characteristics of the mental health professionals available to provide services for mentally ill individuals is unknown.
Describe the distribution and characteristics of medical professionals working in mental health facilities around China.
Information on the numbers and characteristics of health professionals working in mental health facilities in China in 2010 was obtained from the Statistical Information Center of the Ministry of Health and the population-adjusted ratios and characteristics of these mental health professionals were compared across the seven geographic regions of the country.
Among the 757 specialized mental health facilities identified, 649 (86%) were psychiatric hospitals. A total of 68,796 medical professionals (5.16/100,000 population) were working in these facilities, including 20,480 psychiatrists (1.54/100,000) and 35,337 registered nurses (2.65/100,000). Over 98% of these medical professionals worked in psychiatric hospitals. Among the psychiatrists, 29% only had a technical school degree and 14% had no academic degree at all; among the nurses, 46% had no academic qualifications. The duration of employment as a psychiatrist or as a psychiatric nurse was longer among medical professionals working in the economically less dynamic northern parts of the country. The population ratios of licensed physicians and registered nurses working in mental health facilities were significantly higher than average in the relatively wealthy eastern and northeastern parts of the country.
Almost all mental health professionals in China work in specialty psychiatric hospitals. The numbers and geographic distribution of trained mental health professionals in China are grossly inadequate to meet the mental health needs of the population. China has a much smaller mental health workforce per 100,000 residents than other upper-middle-income countries, and the range of professionals who provide mental health services is much narrower.
Focusing heat delivery while minimizing collateral damage to normal tissues is essential for successful nanoparticle-mediated laser-induced thermal cancer therapy. We present thermal maps obtained via magnetic resonance imaging (MRI) characterizing laser heating of a phantom tissue containing a multiwalled carbon nanotube inclusion. The data demonstrate that heating continuously over tens of seconds leads to poor localization (~ 0.5 cm) of the elevated temperature region. By contrast, for the same energy input, heat localization can be reduced to the millimeter rather than centimeter range by increasing the laser power and shortening the pulse duration. The experimental data can be well understood within a simple diffusive heat conduction model. Analysis of the model indicates that to achieve 1 mm or better resolution, heating pulses of ~ 2s or less need to be used with appropriately higher heating power. Modeling these data using a diffusive heat conduction analysis predicts parameters for optimal targeted delivery of heat for ablative therapy.
carbon nanotube; MR thermometry; photothermal therapy; heat localization; diffusive heat model; MR Imaging; proton resonance shift
In the title compound, [Pb(C20H26O2PS2)2(C5H5N)2], the PbII ion is coordinated by two S,S′-bidentate anions and two pyridine molecules. The PbN2S4 coordination geometry approximates to a pentagonal bipyramid with one equatorial site vacant. The N atoms occupy the axial sites. One of the pyridine molecules is disordered over two sets of sites in a 0.907 (7):0.093 (7) ratio and one of the tert-butyl groups is disordered over two sets of sites in a 0.534 (6):0.466 (6) ratio. An intramolecular C—H⋯O interaction occurs in one of the ligands. In the crystal, pairs of short Pb⋯S contacts [3.4018 (11) Å] generate a centrosymmetric dimeric assembly with the distant S atom lying in the region of the vacant coordination site of the metal atom. No directional packing interactions occur.
This study examines clinical predictors of symptom deterioration (relapse/recurrence) at the completion of a clinical intervention trial of depressed, low-income, predominantly Hispanic diabetes patients who were randomized to socio-culturally adapted collaborative depression treatment or usual care and no longer met clinically significant depression criteria at 12 months post-trial baseline.
A sub-cohort of 193 diabetes patients with major depression symptoms at baseline, that were randomized to a 12-month collaborative care intervention (INT) (Problem Solving Therapy and/or pharmacotherapy, telephone symptom monitoring/relapse prevention, behavioral activation and patient navigation support) or enhanced usual care (EUC), and who did not meet major depression criteria at 12 months were subsequently observed over 18 to 24 months.
Post-trial depression symptom deterioration was similar between INT (35.2%) and EUC (35.3%) groups. Among the combined groups, significant predictors of symptom deterioration were baseline history of previous depression and/or dysthymia (odds ratio [OR] =2.66), 12-month PHQ-9 score (OR=1.22), antidepressant treatment receipt during the initial 12-months (OR=2.38), 12-month diabetes symptoms (OR=2.27) and new ICD-9 medical diagnoses in the initial 12 months (OR=1.11) (R2=27%; Max-rescaled R2=37%; Likelihood ratio test, chi-sq=59.79, df=5, p<.0001).
Among predominantly Hispanic diabetes patients in community safety net primary care clinics whose depression had improved over 1 year, more than one third experienced symptom deterioration over the following year. A primary care management depression care protocol that includes ongoing depression symptom monitoring, antidepressant adherence, and diabetes and co-morbid illness monitoring plus depression medication adjustment and behavioral activation may reduce and/or effectively treat depression symptom deterioration.
Depression Recurrence and Relapse; Depression Care Disparities; Depression Symptom Monitoring; Depression and Diabetes; Depression in Hispanics
The structure and ecological roles of the exopolysaccharides (EPSs) from sea ice microorganisms are poorly studied. Here we show that strain SM20310, with an EPS production of 567 mg liter−1, was screened from 110 Arctic sea ice isolates and identified as a Pseudoalteromonas strain. The EPS secreted by SM20310 was purified, and its structural characteristics were studied. The predominant repeating unit of this EPS is a highly complicated α-mannan with a molecular mass greater than 2 × 106 Da. The backbone of the EPS consists of 2-α-, 6-α-mannosyl residues, in which a considerable part of the 6-α-mannosyl residues are branched at the 2 position with either single t-mannosyl residues or two mannosyl residues. The structure of the described EPS is different from the structures of EPSs secreted by other marine bacteria. Analysis of the ecological roles of the identified EPS showed that the EPS could significantly enhance the high-salinity tolerance of SM20310 and improve the survival of SM20310 after freeze-thaw cycles. These results suggest that the EPS secreted by strain SM20310 enables the strain to adapt to the sea ice environment, which is characterized by low temperature, high salinity, and repeated freeze-thaw cycles. In addition to its functions in strain SM20310, this EPS also significantly improved the tolerance of Escherichia coli to freeze-thaw cycles, suggesting that it may have a universal impact on microorganism cryoprotection.
hybrid materials; imaging techniques; magnetic resonance imaging; luminescence; graphene oxide
In the asymmetric unit of the title compound, (C16H38N2O6)[Zn(C3S5)2], two independent cations lie across inversion centers. In one of the cations, the three symmetry-unique O—H groups are disordered over two sets of sites with refined occupancy ratios of 0.701 (9):0.299 (9), 0.671 (8):0.329 (8) and 0.566 (7):0.434 (7). In the anion, the ZnII ion is coordinated in a distorted tetrahedral environment by four S atoms of two chelating 1,3-dithiole-2-thione-4,5-dithiolato ligands. The dihedral angle between the mean planes [maximun deviations = 0.022 (3) and 0.0656 (6) Å] of the two ligands is 87.76 (3)°. An intamolecular O—H⋯O hydrogen bond occurs in the disordered cation. In the crystal, O—H⋯O and O—H⋯S hydrogen bonds link the components into a two-dimensional network parallel to (0-11).
The Flavobacteriaceae bacterium strain P7-3-5 was isolated from intertidal sand of the Yellow Sea, China. Analysis of the 16S rRNA gene sequences showed that strain P7-3-5 formed a distinct phylogenetic lineage within the family Flavobacteriaceae. The genome of strain P7-3-5 was sequenced to facilitate the physiological, ecological, and evolutionary studies of the bacteria within the family Flavobacteriaceae.
The protease-producing bacterium E407-8T was isolated from deep-sea sediment of the South China Sea and has been identified recently as representing a new species, Rheinheimera nanhaiensis. The draft genome of R. nanhaiensis E407-8T consists of 3,987,205 bp and contains 3,730 predicated protein-coding genes, including 82 extracellular peptidase genes.
In the anion of the title compound, (C24H20P)[Fe3(C7H7Te)(CO)12], each Fe0 atom is coordinated by four CO ligands and a Te atom, resulting in a trigonal–bipyramidal coordination environment. The Te atom is coordinated by a 4-methylphenyl group and the Fe0 atoms in a distorted tetrahedral geometry. The average Te—Fe bond length is 2.574 (4) Å.
Cytosine methylation, an epigenetic modification of DNA, is a target of growing interest for developing high throughput profiling technologies. Here we introduce two new, complementary techniques for cytosine methylation profiling utilizing next generation sequencing technology: bisulfite padlock probes (BSPPs) and methyl sensitive cut counting (MSCC). In the first method, we designed a set of ~10,000 BSPPs distributed over the ENCODE pilot project regions to take advantage of existing expression and chromatin immunoprecipitation data. We observed a pattern of low promoter methylation coupled with high gene body methylation in highly expressed genes. Using the second method, MSCC, we gathered genome-scale data for 1.4 million HpaII sites and confirmed that gene body methylation in highly expressed genes is a consistent phenomenon over the entire genome. Our observations highlight the usefulness of techniques which are not inherently or intentionally biased in favor of only profiling particular subsets like CpG islands or promoter regions.
To evaluate the incremental cost-effectiveness of a system-based approach for the management of neonatal jaundice and the prevention of kernicterus in term and late-preterm (≥35 weeks) infants, compared with the traditional practice based on visual inspection and selected bilirubin testing.
Two hypothetical cohorts of 150,000 term and late-preterm neonates were used to compare the costs and outcomes associated with the use of a system-based or traditional practice approach. Data for the evaluation were obtained from the case costing centre at a large teaching hospital in Ontario, supplemented by data from the literature.
The per child cost for the system-based approach cohort was $176, compared with $173 in the traditional practice cohort. The higher cost associated with the system-based cohort reflects increased costs for predischarge screening and treatment and increased postdischarge follow-up visits. These costs are partially offset by reduced costs from fewer emergency room visits, hospital readmissions and kernicterus cases. Compared with the traditional approach, the cost to prevent one kernicterus case using the system-based approach was $570,496, the cost per life year gained was $26,279, and the cost per quality-adjusted life year gained was $65,698.
The cost to prevent one kernicterus case using the system-based approach is much lower than previously reported in the literature.
Comparative effectiveness research; Jaundice; Kernicterus; Neonatology
Right heart failure is the cause of death of most patients with severe pulmonary arterial hypertensive (PAH) disorders, yet little is known about the cellular and molecular causes of right ventricular failure (RVF). We first showed a differential gene expression pattern between normal rat right and left ventricles, and postulated the existence of a molecular right heart failure program that distinguishes RVF from adaptive right ventricular hypertrophy (RVH), and that may differ in some respects from a left heart failure program. By means of microarrays and transcriptional sequencing strategies, we used two models of adaptive RVH to characterize a gene expression pattern reflective of growth and the maintenance of myocardial structure. Moreover, two models of RVF were associated with fibrosis, capillary rarefaction, the decreased expression of genes encoding the angiogenesis factors vascular endothelial growth factor, insulin-like growth factor 1, apelin, and angiopoeitin-1, and the increased expression of genes encoding a set of glycolytic enzymes. The treatment of established RVF with a β-adrenergic receptor blocker reversed RVF, and partly reversed the molecular RVF program. We conclude that normal right and left ventricles demonstrate clearly discernable differences in the expression of mRNA and microRNA, and that RVH and RVF are characterized by distinct patterns of gene expression that relate to cell growth, angiogenesis, and energy metabolism.
pulmonary hypertension; right heart failure; gene expression