Researchers at the USF Health Morsani College of Medicine were awarded $5.6 million of expected funds for a 4-year study from the U.S. Department of Defense to examine why many people with Friedreich’s Ataxia (FA) go on to also develop heart disease, a major cause of death for those with FA.

Principal investigator for the USF study is Thomas McDonald, MD, professor in the Department of Internal Medicine (Division of Cardiology) and the Department of Molecular Pharmacology and Physiology in the USF Health Morsani College of Medicine. Dr. McDonald is also a researcher in the USF Health Heart Institute and director of the USF Health Cardiogenetics Clinic.

“We still don’t have a full understanding of the genetic mutation for Friedrich’s ataxia to determine why so many patients go on to get heart disease – we need to know,” Dr. McDonald said. “The physiology is not well characterized. This study will help us gain a better understanding of the basic mechanisms of the gene that carries FA, and help identify clinical predictors of the FA-associated heart disease.”

The new study dovetails with current work taking place in Dr. McDonald’s lab, including an R56 grant from the National Institutes of Health, which focuses on the fundamental mechanisms of LMNA-associated heart disease passed from one generation to the next — and what can be done to help prevent disease and its consequences.

This FA-heart disease study will follow FA patients and their parents over four years, and will involve careful clinical monitoring of heart health, examination of biomarkers, whole genome sequencing, stem cell modeling of heart tissue, and mitochondrial function studies.

From left, Dr. Kami Kim, Dr. Aarti Patel, Dr. Thomas McDonald, and Dr. Theresa Zesiewicz. Not pictured is Sami Noujaim, PhD.

Spearheading the work in the DoD study is a multidisciplinary team of USF Health experts representing cardiology, genetics, neurology, molecular pharmacology, cardiac electrophysiology and predictive modeling. The diverse expertise will help distinguish the clinical, genetic, and biological factors that contribute to cardiac disease in FA patients. Data from FA families and basic science models will be integrated with clinical data to identify unique factors in the heart that influence the cardiac phenotype and separate cardiac-specific traits from those influencing the neurological phenotype.

“Study results could lead to tools used in patient care settings to identify those FA families most at risk for cardiomyopathy and allow for potential intervention and treatment that could help delay onset of the heart disease,” Dr. McDonald said.

The USF Health interdisciplinary team for the study includes:

• Thomas McDonald, MD: clinical cardiology, molecular pharmacology and cardiogenetics (Division of Cardiology, Department of Internal Medicine, MCOM)
• Aarti Patel, MD: neurocardiogenetics and cardiac imaging (Division of Cardiology, Department of Internal Medicine, MCOM)
• Sami Noujaim, PhD: molecular pharmacology and cardiac electrophysiology (Department of Molecular Pharmacology and Physiology, MCOM)
• Kami Kim, MD: machine learning and clinical predictive modeling (Division of Infectious Diseases, Department of Internal Medicine, MCOM; Center for Global Health Infectious Diseases Research, COPH)
• Theresa Zesiewicz, MD, clinical neurology (Department of Neurology, MCOM)

Dr. Zesiewicz, professor in MCOM and director of the USF Health Ataxia Research Center, has specialized in clinical research and patient care for ataxias and other movement disorders’ for more than 20 years and is recognized as an international expert and leader in the field of hereditary ataxias. Her movement disorders clinic supports the evaluation of over 3,000 patients per year, likely the busiest in the world.

“Dr. Zesiewicz will play a vital role in recruiting research participant and in overseeing neurological assessments of patients as they are longitudinally followed in this study,” Dr. McDonald said.

The funding for the study came from the DoD through its Congressional Directed Medical Research Programs (CDMRP), a section of DoD that funds novel approaches to biomedical research. Link: https://cdmrp.health.mil/

The team will begin recruiting study participants next month.

Photo by Ryan Rossy, USF Health Communications

Dr. Ganesh Halade’s investigation in how “good’’ fats repair the heart could enhance treatment of cardiovascular disease.

TAMPA, FL (April 11, 2022) – New breakthrough research by a University of South Florida lab team describing how certain fats can harm or repair the heart after injury has been accepted by a journal of the American Physiological Society.

A manuscript by Ganesh Halade, PhD, an associate professor of cardiovascular sciences at the USF Health Morsani College of Medicine and a researcher in the USF Health Heart Institute, appears  in the American Journal of Physiology-Heart and Circulatory Physiology, published March 25.

Dr. Ganesh Halade.

Dr. Halade’s research article is titled “Metabolic Transformation of Fat in Obesity Determines the Inflammation Resolving Capacity of Splenocardiac and Cardiorenal Networks in Heart Failure.’’

A key message of the manuscript is how a certain type of healthy fat known as docosahexaenoic acid (DHA) – which is present in Omega-3 fish oil, as found in salmon and tuna – works in tandem with enzymes from the spleen to clear the inflammation in a damaged heart. The spleen plays an important role because it sends immune cells with bags of healthy fat that operates cardiac repair after major injury such as a heart attack.

“So the fat intake needs to be of optimal quality and used by the right enzyme of immune cells,’’ Dr. Halade said. “This is all about cardiac repair and the inflammation clearing molecules (resolution mediators) involved in that repair. It’s essential to the resolution process.’’

Another key message is more about prevention and the genesis of cardiovascular disease: How a chronic and surplus dietary intake of safflower oil (SO, omega-6) can lead to residual inflammation of spleen, kidney, heart, and biosynthesis of pro-inflammatory mediators after an ischemic event. SO is a type of fat commonly used in processed and fast foods that drives chronic inflammation.

“The big question for most people is whether a fat is good or bad, or is omega-3 helpful for heart health?’’ Dr. Halade said. “Everyone is dealing with this question. We’re thinking beyond that by looking at how fat is used in the body after a heart attack and in what forms.’’

“All fats are not created equal,’’ he added, “and despite the extensive literature, the effect of fat intake is the most debated question in obesity, cardiovascular, and cardiorenal research.’’

In his research, Dr. Halade and his team put 100 mice on a 12-week diet of processed (SO) foods to develop residual inflammation and then 50 mice randomized on a primarily DHA-enriched diet for next eight weeks before subjecting to ischemic surgery in mice.

The team made sure both diets had same quantity of calorie per gram of diet. The surplus and chronic intake of SO increased inflammation along with a dysfunctional cardiorenal network. In contrast, DHA increased survival following such heart damage (heart attack).

A result of the study was that the alignment of immune cell enzymes from the spleen and DHA fats are essential to cardiac repair. These so-called “resolution mediators (a family of specialized pro-resolving mediators) is the body’s natural defense process without a negative impact on the body’s physiological response,’’ Dr. Halade said.

Among the key findings in the study:

• DHA supplement improved survival after experimental heart attack to mice
• DHA boost safe clearance of inflammation (resolution) from an injured heart without change in the acute phase of the inflammatory response (day 1), with increased expression of Arg-1, MRC-1, and YM-1 in spleen and infarcted area. These agents are resolution and reparative markers of immune response.
• DHA, along with the body’s natural enzymes, enhanced the ability for the spleen and heart to work together in repairing damage.
• SO primed the spleen and kidney to induce pro-inflammatory pathways and renal inflammation.

“Our next step is to determine the enzymatic machinery or immune responsive enzymes that biosynthesize resolution mediators after ischemic (decreased blood flow commonly called a heart attack) event,’’ Dr. Halade said.

Part of Dr. Halade’s research focuses on how unresolved chronic inflammation and immune responsive metabolic dysregulation contributes to ischemic and non-ischemic heart failure. He is involved in studies of heart failure etiology with an integrative approach focusing on splenic leukocytes and heart, as well as the measurement of inflammatory mediators that impair cardiac repair and resolving lipid mediators that facilitate cardiac repair after a heart attack.

Related story on Dr. Halade’s heart research at USF: /blog/2021/05/10/blocking-lipoxygenase-leads-to-impaired-cardiac-repair-in-acute-heart-failure/

Dr. Halade hopes his latest work can shed new light on controlling chronic inflammation and treating heart failure — a progressively debilitating condition in which weakened or stiff heart muscle cannot pump enough blood to meet the body’s demand for nutrients and oxygen.

It has become a growing public health problem, fueled in part by an aging population, poor diet and obesity epidemic. About 6.2 million adults in the U.S. suffer heart failure, and nearly have died within five years of diagnosis, according to the Federal Centers for Disease Control and Prevention.

The American Physiological Society (APS), which publishes the journal, is a nonprofit devoted to fostering education, scientific research, and dissemination of information in the physiological sciences.

“The editors commend you on your outstanding contribution to the journal,’’ the accepting team wrote to Dr. Halade. “We would like to thank you for contributing this novel and important article.’’

The USF Health study was supported by grants from the National Center for Complementary and Integrative Health (NCCIH, formerly known as National Center for Complementary and Alternative Medicine; (NCCAM), and the National Heart, Lung and Blood Institute.

Written by Kurt Loft

A leading expert on the role of monocytes and macrophages (types of immune cells) in atherosclerosis and other chronic inflammatory conditions delivered the keynote address Nov. 7 at the USF Health Heart Institute’s 2^nd Annual Scientific Colloquium.

Gwendalyn Randolph, PhD, an immunologist by training, began her career by studying how innate immune cells travel around the body and along the way began discovering connections between cardiovascular disease, lipid metabolism and the gut.

USF Health Heart Institute Director Samuel Wickline, MD, with speakers at the Institute’s 2nd Annual Scientific Symposium. From left: David Lominadze, PhD, USF Health professor of surgery; Gwendalyn Randolph, PhD, Unanue Distinguished Professor of Pathology and Immunology at Washington University School of Medicine in St. Louis; Dr. Wickline; and Travis Jackson, PhD, USF Health associate professor of molecular pharmacology and physiology.

For the Heart Institute talk, Dr. Randolph, the Emil R. Unanue Distinguished Professor of Pathology and Immunology at Washington University School of Medicine in St. Louis, focused on research investigating what drives inflammation in atherosclerosis – the most common cause of heart attacks.  She shared her work on the trafficking of immune cells and the lipoproteins that carry cholesterol through the bloodstream to deposit inside the artery walls.

“Dr. Randolph’s work in the field of atherosclerosis has produced novel and important insights into the critical cell types that are responsible for forming atherosclerotic plaques in patients with heart disease,” said Samuel Wickline, MD, professor of cardiology and director of the USF Health Heart Institute. “She also has elucidated the molecular factors that attract these cells to plaques and cause them to grow and become unstable, which leads the plaques to break down and clot. This process can ultimately result in blockage of vessels that supply blood to the heart and brain, causing heart attacks and strokes.”

Research by Dr. Randolph, this year’s keynote speaker at the colloquium, has yielded new insights into how immune cells drive inflammation contributing to atherosclerotic plaques in heart disease.

Mouse model studies by Dr. Randolph and others have shown white blood cells, known as monocytes, contribute to the initial build-up of atherosclerotic plaques.

The cascade of events leading to atherosclerosis can take decades.  Initial damage to the inner wall (endothelium) of arteries under the influence of high cholesterol levels triggers a molecular signal that attracts monocytes to travel from the bloodstream into developing plaques. These recruited monocytes are converted into macrophages that take up (eat) the cholesterol trapped in blood vessels and eventually die off. But before that happens, they stay busy secreting molecules that drive plaque inflammation  and weaken the vessel wall, leading to plaque rupture, clotting, and coronary artery obstruction.

In terms of developing new therapies to halt or reverse atherosclerosis, Dr. Randolph said, her research suggests that upstream targeting of recruited monocytes — either before or just after these immune cells arrive in plaques — may be more beneficial than targeting the fat-laden macrophages known as foam cells. Experiments with fluorescent tracers indicate that monitoring endothelial cells lining the arterial wall may be a way to track monocyte migration, she added.

Thomas McDonald, MD, a professor in the USF Health Morsani College of Medicine’s Department of  Molecular Pharmacology and Physiology and member of the Heart Institute, listens to Dr. Randolph’s talk.

In addition to Dr. Randolph, two new faculty members recruited this summer to the USF Health Heart Institute – Travis Jackson, PhD, and David Lominadze, PhD — provided overviews of their National Institutes of Health-funded research.

Dr. Jackson, an associate professor in the Department of Molecular Pharmacology and Physiology, discussed his translational work in therapeutic hypothermia — investigating ways to optimize cold-shock proteins and cold-stress hormones to increase the benefits of cerebroprotective cooling for traumatic brain injury. Dr. Lominadze, a professor in the Department of Surgery, presented research looking into the interactions of blood cells and the endothelium, with the aim of better understanding the microcirculatory disorders associated with cardiovascular and cerebrovascular diseases.

.

The USF Health Heart Institute is scheduled to move to the new USF Health Morsani College of Medicine building in Water Street Tampa in late February 2020.  Its annual scientific colloquium will be held in the new home next year, and continue to evolve with the growth of the Institute, Dr. Wickline said.

“We will expand the program to cover other topics of interest to the cardiovascular community such as genetic heart diseases, heart failure, peripheral vascular disease, and gene therapy.”

-Photos by Allison Long, USF Health Communications and Marketing

USF Health’s cardiovascular team of faculty, researchers, doctors, nurses, physical therapists, pharmacists and public health professionals continue to develop top-quality research, education and state-of-the-art clinical care to make life better for patients suffering with heart disease. To learn more, click here.

Heart disease is the leading cause of death in the United States. According to American Heart Association (AHA), more than 6 million adults currently live with heart disease.

The number of people living with the condition is only expected to rise. AHA data shows that, by 2030, more than 8 million people could be diagnosed with heart disease.

The numbers are alarming. But, taking basic daily steps may help prevent or reduce heart disease and heart attack.

USF Health medical experts on cardiovascular disease weigh in – providing ten things people can do to keep their heart healthy. They suggest to:

Exercise daily

Vishal Parikh, MD, fellow of the Department of Cardiovascular Sciences at USF Health Morsani College of Medicine, says moderate exercise for at least 30 minutes a day can lower the risk of obesity, high blood pressure, high cholesterol and diabetes.

Quit smoking

Smoking increases the risk of heart disease and heart attack, says Amy Alman, PhD, assistant professor in the Department of Epidemiology and Biostatistics at the USF College of Public Health. “So, say no to smoking,” says Dr. Alman.

Maintain a healthy diet

“A bad diet can put a strain to your heart,” says Ponrathi Athilingam, PhD, assistant professor of cardiology at USF College of Nursing. She suggests considering healthy foods such as fruits, vegetables, whole grains, fish, poultry, lean meats, and nuts to help lower the risk of heart disease. She also recommends eating foods with low trans-fat, saturated fat or sodium.

Manage stress

Dr. Parikh says that stress adds strain to the heart. Constant stress causes behaviors that increase heart disease risks including smoking, excessive alcohol, physical inactivity and lack of sleep. So, he says, “It’s important for people to identify triggers and practice relaxing techniques such as meditation. Something just as simple as laughing may help combat stress.

Advanced genomic monitoring/testing

Kevin Sneed, PharmD, dean of the USF College of Pharmacy, said advanced genomic testing and monitoring, which provides an assessment of cardiovascular genes, helps detect any genetic abnormalities early. “This type of technology would provide awareness, and, most of all, give information for a more targeted intervention to prevent future complications,” says Dr. Sneed.

Maintain a balanced weight

Excessive weight gain increases the risk of cardiovascular disease. According to Center for Disease Control and Prevention, weight gain leads to high cholesterol, high blood pressure and diabetes. “To keep the body in check, remain physically active and, above all, consume whole foods rather than processed foods,” says Mary Soliman, PharmD, assistant professor at USF College of Pharmacy.

Get regular exams

USF Health cardiovascular experts suggest that having regular heart screenings is important – checking the heart rate, blood pressure, body fat and blood sugar. They believe regular screenings keep people informed, which ultimately help prevent heart disease.

Know family history  

Knowing about the family history is important. Having a relative or family member suffering from heart disease, greatly increases one’s risk. “If you have a family history of heart disease or a personal history of heart health risk factors (smoking, obesity, high blood pressure and cholesterol), you may just need to be more diligent in monitoring your heart health,” says Gregory M. Gutierrez, PhD, assistant professor at the USF Health School of Physical Therapy and Rehabilitation Sciences.

Maintain a healthy lifestyle

Keeping an overall healthy lifestyle is the secret to a healthy heart. USF Health experts all agree that lifestyle is key to lowering the risk of heart disease. Exercising, eating healthy, avoiding smoking and second hand-smoking and managing stress, lead to better heart health.

What women need to do

Heart disease causes, symptoms and outcomes may be different in women than in men, says Theresa Beckie, PhD, professor and cardiovascular health researcher at USF College of Nursing and Department of Cardiovascular Sciences in the USF Health Morsani College of Medicine. “Women represent a particularly high-risk phenotype. So, women, especially young women, need to pursue aggressive measures to reduce risks with daily physical activity, a healthy dietary pattern, and stress management,” says Dr. Beckie.

Heart disease and stroke impact so many families across the United States, including our own families here at USF Health.

The American Heart Association is holding its annual Heart Walk to raise funds and awareness for heart disease and stroke, and USF Health faculty, staff and students are gearing up to participate.

The annual event draws thousands from across the Tampa Bay area and is one of nearly 340 events held across the country each year. In total, the national AHA Heart Walk events include more than 1 million walkers.

USF Health faculty, staff and students participate in the local event – details below – by forming teams, making direct donations, sponsoring teams and walking themselves as ways to help raise funds for the American Heart Association and awareness for heart disease and stroke.

While many walk for the cause in general, a large number walk for someone they know battling heart disease or living with stroke. Many are walking in memory of loved ones who have been lost to these diseases. Heart disease and stroke continue to top the list at #1 and #5 for killer diseases in the United States.

USF Health takes active roles in helping AHA’s search for cures, said Phillip J. Marty, PhD, vice president for USF Health Research.

“A foundation of science is what will help find new therapies, treatments and procedures for ending heart disease and stroke,” he said. “We have many promising scientists doing promising research that is laying the groundwork for advances.”

USF Health faculty currently have 11 AHA-funded research awards totaling nearly a million dollars aiming toward the solid science that could lead to cures.

“Much of the work we do at USF falls into the category of translational research, in which basic science researchers work with our clinical researchers to test and translate their work into treatments, cures and preventive measures,” Dr. Marty said. “These collaborative research approaches will ultimately help reduce, and even eradicate, forms of cardiovascular disease and stroke in future generations.”

Click here to register or contribute today!  Participation is not limited to employees and students, so please encourage your family and friends to join a USF team.

And check out a great video for this year’s Heart Walk!

Details:

AHA Heart Walk – Tampa

Saturday, Nov. 7

Raymond James Stadium, 4201 N. Dale Mabry Hwy., Tampa, FL 33607

Festivities Begin at 8:00 a.m. and the walk kicks off at 9:00 a.m.  Plan to arrive early for parking, which is free in the general parking lot south of Raymond James Stadium between Dale Mabry and Himes. The walk route will be 3.2 miles with a one-mile route option.