Preclinical study shows microRNA approach inhibited re-narrowing while healing vessels

Tampa, FL (Aug. 18, 2014) — A new therapy developed by researchers at the University of South Florida (USF) Morsani College of Medicine and Columbia University Medical Center (CUMC) may help reduce the life-threatening complications of interventional cardiovascular disease treatment.

The researchers demonstrated in a rat model that the novel molecular therapy could selectively inhibit blood vessel re-narrowing and simultaneously promote vessel healing following a medical procedure using a balloon catheter to open narrowed or blocked arteries.

Their preclinical study was published in Sept. 2, 2014 in the Journal of Clinical Investigation.

Hana Totary-Jain, PhD, assistant professor of molecular pharmacology and physiology at the USF Health Morsani College of Medicine, was principal investigator for the study.

“This innovative microRNA-based strategy can be used to combine anti-proliferative and pro-healing mechanisms for improved repair of coronary arteries,” said the study’s principal investigator Hana Totary-Jain, PhD, assistant professor of molecular pharmacology and physiology at the USF Health Morsani College of Medicine, who came to USF Health from CUMC last year to join the USF Health Heart Institute.

“The most significant finding of our study is that for the first time we were able to achieve in one fell swoop both the inhibition of cells responsible for re-narrowing of the vessel, and preserving the ‘good’ endothelial cells that protect against thrombosis,” said lead author Gaetano Santulli, MD, PhD, a cardiologist working at CUMC’s College of Physicians & Surgeons.

Angioplasty, the world’s most common medical procedure, opens a narrowed or blocked artery by inserting a small balloon into the blood vessel. If the artery is blocked, a tiny wire-mesh tube, known as a stent, is mounted on the end of the balloon to leave in the vessel when the balloon is removed. The stent holds the artery open and maintains blood flow after angioplasty clears the vessel of fatty deposits. Physicians performed 560,500 angioplasties in the United States in 2011, according to a recent report by the Agency for Healthcare Research and Quality,and, Dr. Santulli said, 70 to 90 percent of all angioplasty patients receive one or more stents.

Together, angioplasty and stenting have helped advance the field of interventional cardiology and save lives.

Drug-eluting stents, first approved for use in the United States in 2003, dramatically reduced rates of restenosis compared to earlier bare metal stents. Medications coating these stents thwart the development of scar tissue causing the treated coronary artery to re-narrow, a complication often requiring another procedure.

While the drug-eluting stent overcame the obstacle of restenosis, research eventually showed that the medications released by the device were not specific — meaning they failed to discriminate between destructive and beneficial cells. The drugs blocked proliferation and migration of vascular smooth muscle cells leading to artery re-narrowing, but they also blocked regrowth of endothelial cells indispensable to healing blood vessel walls disrupted by stent implantation.

Formation of blood clots several months or even years after initial implantation remains a severe, though rare, increased risk associated with the lack of endothelium covering the treated vessel. This risk for late stent clotting, or thrombosis, requires patients to stay on prolonged dual antiplatelet therapy to help prevent life-threatening heart attacks — but not without increasing the odds of major bleeding.

Gaetano Santulli, MD, PhD, of Columbia University Medical Center, was lead author.

With this history in mind, researchers at USF and CUMC harnessed the intrinsic power of microRNAs — master regulators of gene expression affecting many biological processes including cell proliferation — to create a more selective therapy.

Their goal was to inhibit blood vessel re-narrowing and, at the same time, allow endothelial cells to regrow and heal the vessel. They tested the experimental therapy in a rat model of balloon angioplasty injury, and discovered it worked.

Among the findings:

–          As soon as two weeks following arterial injury induced by balloon angioplasty, the injured arteries in the rats receiving microRNA-based therapy were 80 percent covered with new endothelium. In the group receiving a molecular therapy that mimicked drug-eluting stents, endothelial cell coverage remained below 30 percent even after one month. “The difference was quite amazing,” Dr. Totary-Jain said.

–          Measures of blood clotting in the microRNA-based therapy group at two weeks post-injury were reduced to the same levels as in the uninjured control animals.

–          In addition to helping protect against thrombosis-associated clotting, the endothelial cells restored in the treated group appeared to work as well in helping dilate blood vessels as endothelial cells in the vessels of the healthy, untreated control group. “From a clinical point of view, reduced thrombosis and functional vascular responses represent the most promising aspects of the whole study,” Dr. Santulli said.

Dr. Totary-Jain works with Jamie Chilton, PhD, one of the study’s co-authors.

More studies are needed, including implanting stents to test the therapy in other models of atherosclerosis and diabetes.

“This is just the first step, but we are working on tailoring the strategy to be more effective,” Dr. Totary-Jain said. “The combination of this selective therapy with a better stent platform and biodegradable polymer has the potential to revolutionize the future of vascular interventional medicine.”

The USF/CUMC study was supported by the American Heart Association and the National Institutes of Health/National Heart, Lung and Blood Institute.

Article citation: Gaetano Santulli, Anetta Wronska, Kunihiro Uryu, Thomas G. Diacovo, Melanie Gao, Steven O. Marx, Jan Kitajewski, Jamie M. Chilton, Kemal Marc Akat, Thomas Tuschl, Andrew R. Marks, Hana Totary-Jain; “A selective microRNA-based strategy inhibits restenosis while preserving endothelial function;”Journal of Clinical Investigation: 2014;124 (9):4102-4114. DOI: 10.1172/JCI76069.

-USF Health-

USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician’s Group. The University of South Florida is a Top 50 research university in total research expenditures among both public and private institutions nationwide, according to the National Science Foundation. For more information, visit www.health.usf.edu

Tampa, FL (July 27, 2014) — Long-time Tampa cardiologist Xavier E. Prida, MD, joined the USF Health Morsani College of Medicine, Aug. 1 as an assistant professor in the Department of Cardiovascular Sciences where he will play a vital role in clinical education and care.  He comes to USF Health from St. Joseph’s Hospital, where he practiced nearly 27 years.

Dr. Prida will help teach medical students and residents and see patients at USF Health’s south and north campus locations – the South Tampa Center for Advanced Healthcare adjacent to Tampa General Hospital and the Morsani Center for Advanced Healthcare on the USF Tampa campus.  He plans to join the TGH medical staff, providing consultative services and performing procedures in the hospital’s cardiac catheterization laboratory.

Interventional cardiologist Dr. Xavier Prida joins USF Health from St. Joseph’s Hospital, where he practiced for nearly 27 years.

“Dr. Prida is one of the most well-known and respected cardiologists in the Tampa Bay region.  We are fortunate he joined us,” said Arthur Labovitz, MD, chair of the Department of Cardiovascular Sciences and an acting director of the USF Health Heart Institute. “His addition to the department will help advance our primary mission to elevate the level of cardiac care across the region.”

Dr. Prida specializes in consultative cardiology, which offers comprehensive analysis of an individual’s cardiovascular condition and related diseases to help the patient and doctor jointly develop the best treatment plan.  He is an expert in interventional procedures, such as cardiac catheterization, angioplasty and stenting, with a special interest in managing acute coronary syndromes, studying health and disease outcomes, and improving quality of care.

“We have added a superbly trained interventional cardiologist in Dr. Xavier Prida,” said Sally Houston, MD, executive vice president and chief medical officerwith Tampa General Hospital. “He is a welcome addition to our team and will only enhance the outstanding cardiac care we deliver every day at Tampa General.”

Dr. Prida is a fellow of three premier professional societies – the American College of Cardiology, the Society of Cardiovascular Angiography and Intervention, and the American College of Chest Physicians.

At St. Joseph’s since 1987, he held positions as director of the coronary care unit, chief of the Department of Cardiology, director of medical education and quality outcomes, and, most recently, medical director of the adult cardiac catheterization laboratories.

As regional co-director of the American Heart Association’s Mission Lifeline Accelerator program, Dr. Prida was instrumental in helping integrate local systems of care to improve outcomes for patients who suffer a life-threatening type of heart attack known as STEMI, out-of-hospital cardiac arrests, or both.

“Dr. Prida played a key role in working with the community and EMS to get patients into hospital cardiac catheterization labs faster, reducing the time it takes to open blocked arteries,” Dr. Labovitz said.

Dr. Prida received his MD degree from the University of Miami Miller School of Medicine in 1980.  He completed residency training in internal medicine at New York Hospital/Weill Cornell Medical College, and served as assistant chief resident at Memorial Hospital/Sloan Kettering Cancer Institute. Following a fellowship in cardiology at Shands Hospital/ University of Florida College of Medicine, he was appointed instructor of medicine/chief resident in the Department of Medicine there.

Dr. Prida says he looks forward to returning to an academic health center after many years in private practice.

“Students and residents ask questions from different, independent perspectives, and that often opens new avenues of inquiry and discovery,” Dr.  Prida said.  “I’m thankful to the all the patients, institutions, physicians and staff who have educated me over the years.  In this next stage of my career, I want to pass on what I’ve learned from others to help educate the next generation of physician leaders.”

He sees a bright future for USF’s growing clinical cardiology group – the largest in Tampa at the region’s only academic health center.

With Dr. Labovitz’s leadership over the last few years, Dr. Prida said, the USF Health Department of Cardiovascular Sciences “has become a flagship program increasingly relevant to the community it serves.”

                                                                                                                                      -USF Health-
USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician’s Group. The University of South Florida is a Top 50 research university in total research expenditures among both public and private institutions nationwide, according to the National Science Foundation. For more information, visit www.health.usf.edu

USF Health Communications media contacts: 
Lisa Greene, lgreene@health.usf.edu, or (813) 974-4312
Anne DeLotto Baier, abaier@health.usf.edu, or (813) 974-3303

TAMPA, FL (April 9, 2012) – The American College of Cardiology has designated the USF Health Center of Advanced Learning and Simulation (CAMLS) as its first Center of Excellence in Education and Training.

USF Health held the grand opening for its $38 million CAMLS facility in downtown Tampa on March 30. The 90,000 square foot building brings an unprecedented level of technical and teamwork training, simulation and competence assessment under one roof, as well as significant research and device innovation capability.

Among the unique features at CAMLS will be the first hybrid catheterization lab used exclusively for training in the world. The hybrid OR allows health professionals to do both minimally invasive and open surgical procedures in the same operating room, a significant safety benefit for patients.

The hybrid catheterization lab/OR at USF Health CAMLS is the first of its kind in the world used exclusively for training. - Photo by Eric Younghans/USF Health Communications

“The American College of Cardiology is honored to designate CAMLS as our first Center of Excellence in Education and Training,” said ACC CEO Jack Lewin, MD. “CAMLS is leading the way in innovative health technology through the world’s first ever hybrid catheterization laboratory that will be used exclusively for training purposes.

“The ACC is thrilled to be a part of this new simulation program; it benefits the entire catheterization team from nurses and pharmacists to doctors,” Dr. Lewin said. “The type of personalized training offered through the new center will allow our physicians to continue on the path of advancement in quality cardiovascular care leading to better outcomes for patients.”

The ACC designation is in recognition of the realistic education and training facility offered at CAMLS and the broad-based curricula and relevant institutional and program accreditations obtained by USF Health on behalf of CAMLS.

“We’re really excited about our affiliation with the American College of Cardiology and what this partnership means for improving patient outcomes and reducing medical errors,” said Deborah Sutherland, PhD, CEO of CAMLS. “We look forward to working with the ACC to develop a host of events for cardiologists and other health professionals working in the cardiology area over the coming years.”

-USF Health-

USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician’s Group. The University of South Florida is a global research university ranked 34th in federal research expenditures for public universities.

-The American College of Cardiology-

The American College of Cardiology (www.cardiosource.org) is a 40,000-member nonprofit medical society comprised of physicians, surgeons, nurses, physician assistants, pharmacists and practice managers. The College transforms cardiovascular care and improves heart health as it supports and advocates for quality improvement, patient-centered care, payment innovation and professionalism. The ACC bestows credentials upon cardiovascular specialists who meet its stringent qualifications and leads the formulation of health policy, standards and guidelines. It provides professional education, supports and disseminates cardiovascular research, and operates national registries to measure and promote quality.

Media contacts:
Lisa Greene, USF Health Communications, University of South Florida, lgreene@health.usf.edu or (813) 974-4312
Stephanie Abraham, American College of Cardiology, sabraham@acc.org or (202) 375-6296