Breaking News
February 16, 2019 - Men’s porn habits could fuel partners’ eating disorders, study suggests
February 16, 2019 - Rapid progression of age-related diseases may result from formation of vicious cycles
February 16, 2019 - Immune checkpoint molecule protects against future development of cancer
February 16, 2019 - New method produces hydrogels that have properties similar to cells’ environment
February 16, 2019 - $4.1 million funding for heart research on Valentine’s Day
February 16, 2019 - General anesthesia in early infancy unlikely to have lasting effects on developing brains
February 16, 2019 - New breakthroughs for muscular dystrophy research
February 16, 2019 - First Opinion: Embryo editing for higher IQ is a fantasy. Embryo profiling for it is almost here
February 16, 2019 - Vapers develop cancer-related gene deregulation as cigarette smokers
February 16, 2019 - Bringing Antimicrobial Susceptibility Testing (AST) to the Community
February 16, 2019 - Decolonization protocol after hospital discharge can prevent dangerous infections
February 16, 2019 - Therapeutic endoscopy has an expanding role in the treatment of IBD
February 16, 2019 - Intervention can increase exclusive breastfeeding rates
February 16, 2019 - New project explores how gaming technologies can help cancer patients communicate better
February 16, 2019 - Catalyst Biosciences Presents Updated Data from Its Phase 2/3 Trial of Subcutaneous Marzeptacog Alfa (Activated) in Individuals with Hemophilia A or B with Inhibitors at the 12th Annual EAHAD Congress
February 16, 2019 - Rerouting nerves during amputation reduces phantom limb pain before it starts
February 16, 2019 - A Hormone Produced When We Exercise Might Help Fight Alzheimer’s
February 16, 2019 - Millions of British people breathe toxic air travelling to GPs
February 16, 2019 - Conformance of genetic characteristics found to be crucial for longer preservation of kidney graft
February 16, 2019 - Researchers use optogenetic tool to control, visualize receptor signals in neural cells
February 16, 2019 - New reversible antiplatelet therapy could reduce risk of blood clots, prevent cancer metastasis
February 16, 2019 - Testosterone is not the only hormone needed for penis development
February 16, 2019 - FDA Advisory Committee Recommends Approval of Spravato (esketamine) Nasal Spray for Adults with Treatment-Resistant Depression
February 15, 2019 - Heart surgery technology developed at Baptist Health debuts after years of secrecy
February 15, 2019 - Prescription Opioids Double Risk of Triggering Fatal Car Crash
February 15, 2019 - New study helps doctors better understand high blood pressure in pregnant women
February 15, 2019 - Beta wave control in Parkinson’s diseased brain could be a potential therapy
February 15, 2019 - Media representations of love may justify gender-based violence in young people
February 15, 2019 - Yoga May Help With Rheumatoid Arthritis Symptoms, Severity
February 15, 2019 - Obstructive sleep apnea linked to inflammation, organ dysfunction
February 15, 2019 - Master your mind: A challenge from WELL for Life
February 15, 2019 - Why Some Brain Tumors Respond to Immunotherapy
February 15, 2019 - Must-Reads Of The Week From Brianna Labuskes
February 15, 2019 - Researchers uncover novel mechanism and potential new therapeutic target for Alzheimer’s
February 15, 2019 - Genetic variations in a fourth gene associated with higher ALL risk in Hispanic children
February 15, 2019 - Disruptive behavioral problems in kindergarten linked with lower employment earnings in adulthood
February 15, 2019 - New bioengineered device enhances the production of T-cells
February 15, 2019 - HDL proteome behaves like a tiny Velcro ball that is rolling on surfaces
February 15, 2019 - Puerto Rican children more likely to have poor or decreasing use of asthma inhalers
February 15, 2019 - Quality of patient care does not improve after physician-hospital integration
February 15, 2019 - Synopsys release new software for implant design and patient-specific planning
February 15, 2019 - 6 out of 10 hip replacements last 25 years or longer
February 15, 2019 - Health Tip: What You Should Know About Antibiotics
February 15, 2019 - New research challenges medical consensus that adenoids and tonsils significantly shrink during teenage years
February 15, 2019 - Discovery of weakness in a rare cancer could be exploited with drugs
February 15, 2019 - UVA scientists find potential explanation for mysterious cell death in Alzheimer’s, Parkinson’s
February 15, 2019 - New rules requiring female athletes to lower testosterone levels are based on flawed data
February 15, 2019 - Researchers comprehensively sequence the human immune system
February 15, 2019 - Researchers study animal venoms to identify new medicines for treating diseases
February 15, 2019 - Movement of wrist bones revealed by MRI and computer modeling
February 15, 2019 - Philips introduces new premium digital X-ray room to help shorten patient wait times
February 15, 2019 - Women fare worse than men following aortic heart surgery, study finds
February 15, 2019 - High-protein and low-calorie diet helps older adults lose weight safely, shows study
February 15, 2019 - Drug microdosing effects may not measure up to big expectations
February 15, 2019 - Discharged, Dismissed: ERs Often Miss Chance To Set Overdose Survivors On ‘Better Path’
February 15, 2019 - A digitized lab environment to be showcased at smartLAB 2019
February 15, 2019 - Scientists uncover main mechanisms of fluconazole drug resistance
February 15, 2019 - New study seeks to understand how colibactin causes cancer
February 15, 2019 - Photoacoustic imaging accurately measures the temperature of deep tissues
February 15, 2019 - Large study finds no association between phthalate exposure and breast cancer risk
February 15, 2019 - New research explains presence of ‘natural’ magnetism in human cells
February 15, 2019 - Bio-Rad launches new digital PCR system and kit for monitoring treatment response in CML patients
February 15, 2019 - Excessive daytime sleepiness in OSA patients linked to greater risk for cardiovascular diseases
February 15, 2019 - Scientists shed light on damaging cell effects linked to aging
February 15, 2019 - Celiac disease may be caused by stomach bug in childhood
February 15, 2019 - NHS performance figures highlight the true scale of Emergency Department crisis
February 15, 2019 - High intensity exercise may improve health by increasing gut microbiota diversity
February 15, 2019 - Apellis’ APL-2 Receives Orphan Drug Designation from the FDA for the Treatment of Autoimmune Hemolytic Anemia
February 15, 2019 - Couples creating art or playing board games release ‘love hormone’
February 15, 2019 - Glimpsing The Future At Gargantuan Health Tech Showcase
February 15, 2019 - Common herbicide found to increase the risk of lymphoma
February 15, 2019 - Over-abundance of energy to cells could increase cancer risk
February 15, 2019 - Oxford Genetics appoints Jocelyne Bath as new Chief Operating Officer
February 15, 2019 - Castration-resistant metastatic prostate cancer responds to combination of immune checkpoint inhibitors
February 15, 2019 - Large-scale clinical trial begins to study liver transplantation between people with HIV
February 15, 2019 - Cannabis use among adolescents linked with increased risk of depression in adulthood
February 15, 2019 - Fractures, head injuries common in electric scooter accidents, UCLA study finds
February 15, 2019 - Prenatal maternal depression has important consequences for infant temperament, study shows
February 15, 2019 - Stereotactic body radiotherapy effective in treating men with low- or intermediate-risk prostate cancer
February 15, 2019 - Zogenix Submits New Drug Application to U.S. Food & Drug Administration for Fintepla for the Treatment of Dravet Syndrome
Researchers describe underlying mechanisms of congestive heart failure

Researchers describe underlying mechanisms of congestive heart failure

image_pdfDownload PDFimage_print

Congestive heart failure is a terminal disease that affects nearly 6 million Americans. Yet its management is limited to symptomatic treatments because the causal mechanisms of congestive heart failure — including its most common form, ischemic cardiomyopathy — are not known. Ischemic cardiomyopathy is the result of restricted blood flow in coronary arteries, as occurs during a heart attack, which starves the heart muscle of oxygen.

Researchers at the University of Alabama at Birmingham have now described an underlying mechanism that reprograms the hearts of patients with ischemic cardiomyopathy, a process that differs from patients with other forms of heart failure, collectively known as dilated (non-ischemic) cardiomyopathies. This points the way toward future personalized care for ischemic cardiomyopathy.

The study used heart tissue samples collected at UAB during surgeries to implant small mechanical pumps alongside the hearts of patients with end-stage heart failure that assist in the pumping of blood. As a routine part of this procedure, a small piece of heart tissue is excised and ultimately discarded as medical waste. The current study acquired these samples from the left ventricles of five ischemic cardiomyopathy patients and six non-ischemic cardiomyopathy patients, all men between ages 49 and 70.

The research team, led by Adam Wende, Ph.D., assistant professor in the UAB Department of Pathology, found that epigenetic changes in ischemic cardiomyopathy hearts likely reprogram the heart’s metabolism and alter cellular remodeling in the heart. Epigenetics is a field that describes molecular modifications known to alter the activity of genes without changing their DNA sequence.

One well-established epigenetic change is the addition or removal of methyl groups to the cytosine bases of DNA. Generally, hyper-methylation is associated with reduction of gene expression, and conversely, hypo-methylation correlates with increased gene expression.

Wende and colleagues found an epigenetic signature in the heart of patients with ischemic cardiomyopathy that differed from the non-ischemic hearts. Furthermore, this signature was found to reflect a long-known metabolic change in ischemic cardiomyopathy, where the heart’s preference of metabolic fuel switches from using oxygen to produce energy in cells, as healthy hearts do, to an anaerobic metabolism that does not need oxygen. This anaerobic metabolic preference is seen in fetal hearts; however, after birth, the baby’s heart quickly changes to oxidative metabolism.

“Altogether, we believe that epigenetic changes encode a so-called ‘metabolic plasticity’ in failing hearts, the reversal of which may repair the ischemic and failing heart,” Wende said.

The researchers found that increased DNA methylation correlated with reduced expression of genes involved in oxidative metabolism. The transcription factor KLF15 is an upstream regulator of metabolic gene expression, which the researchers found is suppressed by the epigenetic regulator EZH2. Conversely, the researchers also found hypo-methylation of anaerobic glycolytic metabolic genes.

This contribution by EZH2 offers a new molecular target for further mechanistic studies that may aid precision-based heart disease therapies. Of note, co-author Sooryanarayana Varambally, who has spent over 15 years studying this protein, has already made progress using small-molecular inhibitors to regulate EZH2 to treat various cancers.

The Wende-led study, now published in Nature – Laboratory Investigation, employed a wide array of bioinformatics tools. First author Mark Pepin used publicly available programs to create a fully automated computational pipeline, which is provided as an online supplement to the paper. This protocol, written in the R programming language, allowed the investigators to both analyze their multi-Omics datasets and compare their findings to those of animal-based studies and public data repositories. “Supplying the coding scripts,” Wende said, “is our way of demonstrating the rigor and reproducibility that should be expected of any bioinformatics study.”

Pepin is a sixth-year M.D.-Ph.D. student at UAB and is currently completing the Ph.D. portion of his training in the Medical Scientist Training Program.

The UAB team also performed cell culture experiments showing repression of KLF15 after EZH2 over-expression in rat cardiomyoblasts, and they demonstrated that EZH2 over-expression depended on EZH2’s having an intact SET catalytic domain.

Source:

https://www.uab.edu/news/research/item/9666-epigenetic-reprogramming-of-human-hearts-found-in-congestive-heart-failure

About author

Related Articles