Breaking News
April 25, 2019 - The Current issue of “The view from here” is concerned with Partnerships and Alliances
April 25, 2019 - Imaging method reveals long-lived patterns in cells of the eye
April 25, 2019 - Podcast: KHN’s ‘What The Health?’ The Abortion Wars Rage On
April 25, 2019 - Prolonged exposure therapy is more effective in treating veterans with PTSD, alcohol use disorder
April 24, 2019 - Our artificial cornea breakthrough could lead to self-assembling organs
April 24, 2019 - A Stanford black, female, gay surgery resident speaks out
April 24, 2019 - Donna Lynne on Extreme Sports, Lessons From the '60s, and Taking CUIMC to the Next Level
April 24, 2019 - Pain Clinics’ Doctors Needlessly Tested Hundreds Of Urine Samples, Court Records Show
April 24, 2019 - Researchers uncover potential clue to halt destruction of nerve cells in people with ALS
April 24, 2019 - Study uncovers reasons for poor mental health in bisexual people
April 24, 2019 - Screenings, interventions, and referrals can help adolescents overcome substance abuse
April 24, 2019 - Febrile seizures following vaccination are self-resolving and not dangerous
April 24, 2019 - Flow-UV inline UV-Visible spectrometer monitors dispersion in real time
April 24, 2019 - Rates of Marijuana Use in Cancer Patients on the Rise in U.S.
April 24, 2019 - Versatile drug may protect baby from hazards of intraamniotic infections
April 24, 2019 - Financial transparency may diminish trust in doctors, new study finds
April 24, 2019 - Calling all Riders: Velocity Extends Free Registration 
April 24, 2019 - The Homeless Are Dying In Record Numbers On The Streets Of L.A.
April 24, 2019 - Blocking BRAF ubiquitination may be an effective treatment approach in melanoma
April 24, 2019 - Simple mobility test helps predict hospital readmission in elderly heart attack patients
April 24, 2019 - Novel fluorescence imaging system helps surgeons remove small ovarian tumors
April 24, 2019 - Uncovering the Structure of HIV Integrase to Inform Drug Discovery
April 24, 2019 - Medical Marijuana Use Rising Among Cancer Patients
April 24, 2019 - Artificial intelligence approach optimizes embryo selection for IVF
April 24, 2019 - Doctor or detective? Sleuthing mysteries in medical school
April 24, 2019 - CUIMC Community Gives Blood During Spring 2019 Columbia University Blood Drive
April 24, 2019 - Americans Overwhelmingly Want Federal Protections Against Surprise Medical Bills
April 24, 2019 - Making Laboratories More Efficient with the Most Modern LIMS on the Market
April 24, 2019 - Treating cancer patients with personalized, combination therapies improves outcomes
April 24, 2019 - Researchers engineer new molecules to help stop lung cancer
April 24, 2019 - Acupuncture can be a wonderful tool for preventing number of diseases
April 24, 2019 - Daily life disability before hip replacement may predict poor post-operative outcomes
April 24, 2019 - Study finds involuntary staying in housing estates to be a potential health risk
April 24, 2019 - Older kidney disease patients starting dialysis die at higher rates than previously thought
April 24, 2019 - Time-restricted eating shows promise for controlling blood glucose levels
April 24, 2019 - Ambiguous genitalia in newborns may be more common than previously thought
April 24, 2019 - Research provides important insight on the brain-body connection
April 24, 2019 - In 10 Years, Half Of Middle-Income Elders Won’t Be Able To Afford Housing, Medical Care
April 24, 2019 - Researchers study how E. coli clones have become major cause of drug-resistant infections
April 24, 2019 - Bacterial and fungal toxins found in popular electronic cigarettes
April 24, 2019 - Factors affecting absorption of ‘sunshine vitamin’ during spring/summer months
April 24, 2019 - Texting helps improve medication adherence, health outcomes for patients with schizophrenia
April 24, 2019 - Cochrane Review looks at different ways to use nicotine replacement therapies
April 24, 2019 - New review on relationship between COPD and Type 2 diabetes
April 24, 2019 - Brain areas linked to memory and emotion aid odor navigation in humans
April 24, 2019 - Brain stimulation reverses age-related memory loss
April 24, 2019 - Amid Opioid Prescriber Crackdown, Health Officials Reach Out To Pain Patients
April 24, 2019 - $4 million NIH award will help establish UCI Skin Biology Resource-based Center
April 24, 2019 - Cancer drugs reprogram genes in breast tumors to prevent endocrine resistance, finds study
April 24, 2019 - Combination-imaging technique provides new window into macaque brain connections
April 24, 2019 - Researchers identify new allergen responsible for allergy to durum wheat
April 24, 2019 - Researchers define role of rare, influential cells in the bone marrow
April 24, 2019 - DNA rearrangement may predict poor outcomes in multiple myeloma
April 24, 2019 - FDA Approves Skyrizi (risankizumab-rzaa) for Moderate to Severe Plaque Psoriasis
April 24, 2019 - Combination therapy might be beneficial in schizophrenia
April 24, 2019 - Blood test can help match cancer patients to early phase clinical trials
April 24, 2019 - Women tend to underreport snoring and underestimate its loudness
April 24, 2019 - Comprehensive molecular test introduced for diagnosis of malaria caused by P. vivax parasites
April 24, 2019 - New range prediction approach increases accuracy, safety and tolerability of proton therapy
April 24, 2019 - Need for Sedation Up for Regular Cannabis Users
April 24, 2019 - Lack of access to antibiotics is a major global health challenge
April 24, 2019 - New study provides better understanding on safety of deworming programs
April 24, 2019 - EEG used to detect impact of maternal stress on neurodevelopment in 2-month-old infants
April 24, 2019 - FDA Approves First Generic Naloxone Nasal Spray Against Opioid Overdose
April 24, 2019 - A new way of finding compounds that prevent aging
April 24, 2019 - Mechanical training makes synthetic hydrogels perform more like muscle
April 24, 2019 - Study provides new insights into regulatory T cells’ role in protecting against autoimmune disease
April 24, 2019 - Pregnant women with type 1 diabetes are at greater risk of preterm birth
April 24, 2019 - ‘Tummy tuck’ can be safely performed in obese patients with no increase in complications
April 23, 2019 - ‘First’ 3-D print of heart with human tissue, vessels unveiled
April 23, 2019 - Which blood-based method works best to detect TB?
April 23, 2019 - Gene therapy cures infants suffering from ‘bubble boy’ immune disease
April 23, 2019 - Chemical-sampling wristbands detect similar exposures across three continents
April 23, 2019 - Management of Residual Limb Pain
April 23, 2019 - Molecular clock influences immune cell responses
April 23, 2019 - On the importance of culture, partnerships and diversity at the Dean’s Lecture Series
April 23, 2019 - Siddhartha Mukherjee Receives Lewis Thomas Prize for Writing About Science
April 23, 2019 - Dengue mosquito poses greatest danger of spreading Zika virus in Australia
April 23, 2019 - Scientists identify 104 high-risk genes for schizophrenia
April 23, 2019 - Abdominal etching can help patients to get classic ‘six-pack abs’ physique
Diseased heart muscle cells have abnormally shortened telomeres, researchers find

Diseased heart muscle cells have abnormally shortened telomeres, researchers find

image_pdfDownload PDFimage_print
Human chromosomes (grey) capped by telomeres (white). Credit: PD-NASA; PD-USGOV-NASA

People with a form of heart disease called cardiomyopathy have abnormally short telomeres in heart muscle cells responsible for contraction, according to a new study by researchers at the Stanford University School of Medicine.

A telomere is a DNA sequence that serves as a protective cap on the ends of chromosomes.

The finding dovetails with a previous study showing that people with Duchenne muscular dystrophy, a genetic muscle-wasting disease, also have short telomeres in their heart muscle cells, or cardiomyocytes. These patients often die at an early age from heart failure.

Although it’s not yet known whether the stunted telomeres directly affect the function of the cardiomyocytes or arise as a result of heart failure, the finding opens the door to an intriguing line of research and drug discovery. It also may one day allow researchers and clinicians to identify people at risk for heart failure due to cardiomyopathy.

“The shortening of telomeres in cardiomyocytes appears to be a reliable hallmark of cardiac failures that arise due to genetic defects, and it’s very specific to cells that require the missing contractile proteins such as dystrophin, troponin T or myosin heavy chain, among others,” said Helen Blau, Ph.D., professor of microbiology and immunology and member of the Stanford Cardiovascular Institute.

Blau, the Donald E. and Delia B. Baxter Foundation Professor and director of the Baxter Laboratory for Stem Cell Biology, is the senior author of the study, which will be published online Aug. 27 in Proceedings of the National Academy of Sciences. Alex Chang, Ph.D., an instructor of cardiovascular medicine and of microbiology and immunology, is the lead author.

Shortening with cell division

In most cells, telomeres naturally shorten each time the cell divides. But cardiomyocytes divide infrequently, and their telomere lengths remain relatively stable throughout one’s life.

In humans, Duchenne muscular dystrophy, which is caused by a mutation in the dystrophin gene, is characterized by progressive muscle weakness and eventual death due to cardiac complications. In earlier work, Blau and her colleagues observed that although mice with the corresponding mutation in dystrophin displayed the muscle wasting symptoms, their hearts functioned normally. The researchers realized that a key difference between humans and mice is the length of each species’ telomeres: Human telomeres are relatively short at 5-15 kilobases, but mice have telomeres approaching 40 kilobases. When the investigators introduced a second mutation in the mice that reduced telomere length to more closely match that of humans, the animals began to display the typical symptoms of the disease, including heart failure.

A subsequent study in the Blau lab found that, in mice, telomere shortening triggered a DNA-damage response that compromised the function of the cells’ energy generators, or mitochondria. As a result, cardiomyocytes were unable to efficiently pump blood throughout the body.

“Because we found in a previous study that cardiomyocytes from boys who had died of Duchenne muscular dystrophy had telomeres that were about 50 percent shorter than those from individuals without the disease,” Blau said, “we wondered whether people with other genetic heart conditions, such as cardiomyopathies, might also have cardiomyocytes with abnormally shortened telomeres.” Blau and Chang collaborated with several other members of Stanford’s Cardiovascular Institute to investigate the question.

A cardiomyopathy is a condition in which the heart is unusually large, thickened or stiff. This affects its ability to pump blood effectively. One out of every 500-2,500 people worldwide is affected, and cardiomyopathies are a leading cause for heart transplantation. Dilated cardiomyopathy occurs when the left ventricle is enlarged, while hypertrophic cardiomyopathy is caused by a thickening of the heart muscle.

Chang compared the telomere length in cardiomyocytes from 11 patients with dilated or hypertrophic cardiomyopathy due to genetic mutations with nine people who had died from causes unrelated to heart disease. He found that telomeres from the cardiomyopathy patients were about 25-40 percent shorter than those of the control subjects. In contrast, the telomere length in nonbeating heart cells of the blood vessels did not vary significantly between the two groups.

Chang saw similar results in cardiomyocytes generated from induced pluripotent stem cells: Those generated from people with cardiomyopathies had significantly shorter telomeres than those generated from unaffected relatives.

“Within 20 days we could see the telomere shortening happening in the laboratory-grown cardiomyocytes from diseased patients, suggesting this is a cell-intrinsic property,” Blau said.

The ability to use iPS cell technology to generate affected cardiomyocytes also means that it should be possible to quickly and easily test for compounds or drugs that interfere with the telomere shortening with a view to finding drugs to abrogate the disease in humans, the researchers believe.

“Now we can study this phenomenon in the lab in real time and start to ask questions about cause and effect,” Blau said. “We’d love to know, for example, how this shortening might impact the DNA damage response, mitochondrial dysfunction and cell-death pathways. It opens up a whole new line of investigation.”


Explore further:
DNA damage response links short telomeres, heart disorder in Duchenne muscular dystrophy

More information:
Alex C. Y. Chang el al., “Telomere shortening is a hallmark of genetic cardiomyopathies,” PNAS (2018). www.pnas.org/cgi/doi/10.1073/pnas.1714538115

Journal reference:
Proceedings of the National Academy of Sciences

Provided by:
Stanford University Medical Center

Tagged with:

About author

Related Articles