Northeastern researchers identify 36 new genes implicated in cardiac diseaseMarch 07, 2018
One in four deaths in the United States each year are due to heart disease, according to the Centers for Disease Control and Prevention. It's the leading killer of both men and women, but the disease's genetic complexity makes it difficult to treat.
In a recently-published paper in npj Systems Biology and Applications, Northeastern physics professor Alain Karma and his colleagues describe their discovery of 36 previously unknown genes implicated in heart failure. The team confirmed that one of those genes plays a causal role in cardiac hypertrophy--abnormal thickening of the heart muscle--which can lead to heart failure.
"This is an exciting direction for personalized medicine, and also for identifying genes and therapeutic targets for complex diseases that involve many genes," Karma said.
The ultimate goal is to create personalized therapeutic drugs to reverse heart disease. Researchers are probably still a decade away from achieving that sort of tailored therapy, Karma said. But companies interested in developing such drugs can use the method he and his colleagues developed and the genes they identified to get a step closer.
The framework described in the paper can also be used to predict whether individuals suffering from a particular disease will respond to a given drug treatment, said lead author Marc Santolini, a postdoctoral research associate at Northeastern's Center for Complex Network Research.
"The method can predict beforehand whether a patient should be prescribed a different drug using just a simple blood test. This would save time and accelerate the therapy," Santolini said. "In general, this research highlights the importance of personalized approaches to uncover novel disease genes and better understand disease processes."
The traditional approach to finding genes related to heart disease works like this: Researchers take donated hearts from people who died unexpectedly but were previously healthy. They analyze the gene expression--that is, the amount of messenger RNA and proteins--produced by the genes of healthy hearts and compare it with the gene expression of sick hearts explanted from end-stage heart failure patients undergoing heart transplant.
"You see a different gene expression profile," Karma said. For example, if a gene found in the sick hearts expresses twice the amount of RNA as it did in the healthy hearts, it might be relevant to the disease. But so far, Karma said this method hasn't been very successful in finding important genes.
His team took an entirely different approach--using the Hybrid Mouse Diversity Panel, a collection of 100 genetically different strains of mice that can be used to analyze the genetic and environmental factors underlying complex traits. Within each strain, the mice are inbred, making them all identical twins on a genetic level.
Researchers took two mice from the same strain and gave one of them a stressor drug that induces heart failure. They then compared the stressed mouse's gene expression with its non-stressed twin. Since the mice have the same genome, they were able to pinpoint individual genes that changed expression as a direct result of the heart stressor. The researchers identified 36 such genes.
Many of these genes were previously unknown to be implicated in heart failure. Karma said one of them is known as a transcription factor, meaning it controls the expression of many other genes. The researchers confirmed the gene's role by using molecular biology techniques to silence it and observe the resulting changes of expression. They found the transcription factor gene was directly connected to a whole network of proteins known to play a role in cardiac hypertrophy.
One of the genes Karma found, called RFFL, was previously known to researchers to be implicated in other cardiac processes. However, it was not known to be related to hypertrophy, said Gideon Koren, a physician and director of the Cardiovascular Research Center at Rhode Island Hospital & the Cardiovascular Institute. Koren has been studying RFFL in his lab for the past two years.
"All of the sudden, this study reveals the gene is important for the hypertrophic trait," Koren said. "We now think that RFFL is an important node that can cross-talk with cardiac hypertrophy failure and cardiac excitation." Cardiac excitation is the process that enables the chambers of the heart to contract and relax. "That was something that we wouldn't have explored, given what we knew about RFFL," Koren added.
As a next step, Karma said the new method could be tested on human stem cells, which have the same genetic code as the person they came from and can be induced to have similar gene expression patterns as heart cells.
"When you are comparing two populations of cells from the same person--one that has been controlled and one that has been under the effect of a drug or stressor--you can compare the change of gene expression in a personalized way," Karma said.
Related Heart Disease Articles:
People living in parts of Ontario with better access to preventive health care had lower rates of cardiac events compared to residents of regions with less access, found a new study published in CMAJ (Canadian Medical Association Journal).
Improving physical function among older adults with heart disease helps heart health and even the oldest have a better quality of life and greater independence.
Nearly half of all deaths due to heart disease, stroke, and type 2 diabetes in the US in 2012 were associated with suboptimal consumption of certain dietary factors, according to a study appearing in the March 7 issue of JAMA.
For the first time, researchers have pinpointed a type of heart fat, linked it to a risk factor for heart disease and shown that menopausal status and estrogen levels are critical modifying factors of its associated risk in women.
Pregnant women with congenital heart defects or type 2 diabetes have a higher risk of giving birth to babies with severe congenital heart disease and should be monitored closely in the prenatal period, according to a study published in CMAJ.
A novel heart valve replacement method is revealed today that offers hope for the thousands of patients with rheumatic heart disease who need the procedure each year.
For patients age 50 and younger, the risk of premature death after a heart attack has dropped significantly, but their risk is still almost twice as high when compared to the general population, largely due to heart disease and other smoking-related diseases The risk of heart attack can be greatly reduced by quitting smoking, exercising and following a healthy diet.
Oranges and other citrus fruits are good for you -- they contain plenty of vitamins and substances, such as antioxidants, that can help keep you healthy.
A history of gallstone disease was linked to a 23 percent increased risk of developing coronary heart disease.
Coronary heart disease is one of the leading causes of death in the United States.
Related Heart Disease Reading:
Prevent and Reverse Heart Disease: The Revolutionary, Scientifically Proven, Nutrition-Based Cure
by Caldwell B. Esselstyn Jr. (Author)
The New York Times bestselling guide to the lifesaving diet that can both prevent and help reverse the effects of heart disease
Based on the groundbreaking results of his twenty-year nutritional study, Prevent and Reverse Heart Disease by Dr. Caldwell Esselstyn illustrates that a plant-based, oil-free diet can not only prevent the progression of heart disease but can also reverse its effects. Dr. Esselstyn is an internationally known surgeon, researcher and former clinician at the Cleveland Clinic and a featured expert in the acclaimed documentary Forks... View Details
Pathophysiology of Heart Disease: A Collaborative Project of Medical Students and Faculty
by Leonard S. Lilly MD (Author)
Publisher’s Note: Products purchased from 3rd Party sellers are not guaranteed by the Publisher for quality, authenticity, or access to any online entitlements included with the product.
Specifically designed to prepare medical students for their initial encounters with patients with heart disease, this award-winning text bridges basic cardiac physiology with clinical care. Written by internationally recognized Harvard Medical School faculty and select medical students, Pathophysiology of Heart Disease, Sixth Edition provides a solid foundation of knowledge... View Details
The End of Heart Disease: The Eat to Live Plan to Prevent and Reverse Heart Disease
by Dr. Joel Fuhrman (Author)
The New York Times bestselling author of Eat to Live, Super Immunity, The End of Diabetes, and The End of Dieting presents a scientifically proven, practical program to prevent and reverse heart disease, the leading cause of death in America—coinciding with the author’s new medical study revealing headline-making findings.
Dr. Joel Fuhrman, one of the country’s leading experts on preventative medicine, offers his science-backed nutritional plan that addresses the leading cause of death in America: heart disease. An expert in the science of food, Dr.... View Details
Dr. Dean Ornish's Program for Reversing Heart Disease: The Only System Scientifically Proven to Reverse Heart Disease Without Drugs or Surgery
by Dean Ornish (Author)
Dr. Dean Ornish's Program for Reversing Heart Disease: The Only System Scientifically Proven to Reverse Heart Disease Without Drugs or Surgery View Details
The Simple Heart Cure: The 90-Day Program to Stop and Reverse Heart Disease
by Chauncey Crandall (Author)
Heart disease kills more people than any other medical condition. And no one is more aware of this than top cardiologist Dr. Chauncey Crandall, who has performed over 40,000 heart procedures during his career.
In his new book, The Simple Heart Cure, you’ll find this top doc’s groundbreaking approach to preventing and reversing heart disease an approach honed by his study of foreign cultures free of heart disease and decades of experience helping patients achieve a healthier heart at any age.
Dr. Crandall is living proof of his program’s success. At the age of... View Details
What Your Doctor May Not Tell You about Heart Disease
by Mark Houston (Author)
Coronary heart disease has long been the number one killer in this country, and for decades, we have been told about five basic risk factors: elevated cholesterol, high blood pressure, diabetes, obesity, and smoking. But the truth is that heart disease is much more complex-- with close to 400 risk factors!
In this innovative guide, Dr. Mark Houston helps readers discover the causes of heart disease, how to prevent and treat its debilitating effects via nutrition, nutritional supplements, exercise, weight management, and lays to rest to various myths (cholesterol is not the... View Details
The Prevent and Reverse Heart Disease Cookbook: Over 125 Delicious, Life-Changing, Plant-Based Recipes
by Ann Crile Esselstyn (Author), Jane Esselstyn (Author)
The long-awaited cookbook companion to the revolutionary New York Times bestseller Prevent and Reverse Heart Disease.
“I hope you'll treat yourself to one of these recipes and just open that door. I guarantee you won't close it!"
—Samuel L. Jackson
Hundreds of thousands of readers have been inspired to turn their lives around by Dr. Caldwell B. Esselstyn’s Jr.’s bestseller, Prevent and Reverse Heart Disease. The plant-based nutrition plan Dr. Esselstyn advocates based on his twenty-year nutritional study—the most... View Details
The 30-Day Heart Tune-Up: A Breakthrough Medical Plan to Prevent and Reverse Heart Disease
by Steven Masley (Author), Douglas D. Schocken (Foreword)
THE 30-DAY HEART TUNE-UP takes readers step by step through a revolutionary program to tune up their hearts, energy, waistlines, and sex lives, with 60 delicious recipes to help jump-start a heart-healthy diet. Cardiovascular disease is the #1 killer of Americans today. But, the good news is that everyone-regardless of size, genetics, gender, or age-can treat arterial plaque and prevent heart attacks and strokes with this book. The keys to the program are shrinking arterial plaque, improving circulation, and strengthening your heartbeat. The tools in this book include... View Details
A Woman's Guide to Living with Heart Disease
by Carolyn Thomas (Author), Martha Gulati (Foreword)
Heart disease is the leading cause of death for women worldwide. Yet most people are still unaware that heart disease is not just a man’s problem. Carolyn Thomas, a heart attack survivor herself, is on a mission to educate women about their heart health. Based on her popular Heart Sisters blog, which has attracted more than 10 million views from readers in 190 countries, A Woman's Guide to Living with Heart Disease combines personal experience and medical knowledge to help women learn how to understand and manage a catastrophic diagnosis.
In A Woman's Guide to... View Details
Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 2-Volume Set, 11e
by Douglas P. Zipes MD (Author), Peter Libby MD PhD (Author), Robert O. Bonow MD MS (Author), Douglas L. Mann MD (Author), Gordon F. Tomaselli MD (Author)
Trusted by generations of cardiologists for the latest, most reliable guidance in the field, Braunwald’s Heart Disease, 11th Edition, remains your #1 source of information on rapidly changing clinical science, clinical and translational research, and evidence-based medicine. This award-winning text has been completely updated, providing a superior multimedia reference for every aspect of this fast-changing field, including new material about almost every topic in cardiology.A unique update program by Dr. Braunwald creates a "living textbook" by featuring... View Details