Heart Research Points Way to Longer Lives

By Ben Boulden


Feb. 25, 2013 | Cardiovascular research at the University of Arkansas for Medical Sciences (UAMS) could one day lead to a test for aneurysms, an annual treatment for hypertension and a treatment for inflammation that accompanies a host of diseases.

These discoveries in turn could lengthen the lives and improve the quality of life of many Arkansans and others.

“Cardiovascular disease is the number one killer in the nation,” said Steve Post, Ph.D., director of the Experimental Pathology Division in the UAMS College of Medicine. “In general, Arkansas is close to the top of states with the highest incidence of heart disease.”

February is American Heart Month, a month during which health professionals try to refocus attention on cardiovascular disease and care.

Aneurysm Risk

Post is one of the faculty members with research laboratories that belong to the UAMS Cardiovascular Center, which also includes clinicians.

He and his research team have been studying atherosclerosis for several years and are looking at the role of an immune receptor in disease, which causes arteries to harden. Loss of this receptor appears to predispose to aneurysms. Taken to its conclusion, the research could lead to a test that helps physicians determine which aneurysms are likely to rupture and which are not.

One focus of Post’s research is aneurysms in the aorta. Aneurysms may play a larger role in heart disease deaths than usually assumed. Post said statistics actually may underestimate how many fatalities are attributed to an aortic aneurysm because the symptoms of a ruptured aneurysm are similar to those of a heart attack.

“Surgery to repair an aneurysm is extremely high risk,” Post said. “We have no way of telling which aneurysms are prone to rupture and good candidates for surgery and which are not.” Having a test that helps sort that out could greatly lower that risk.

Platelets, Inflammation and Clots

Blood platelets play a role in the inflammation that occurs in heart tissue after someone has a heart attack.

According to research efforts led by Jerry Ware, Ph.D., UAMS College of Medicine professor, blood platelets sticking to immune cells are a factor in causing inflammation. That inflammation can impede the flow of blood back into the heart tissue and delay or prevent recovery.

Inflammation plays a role in other diseases like rheumatoid arthritis, diabetes, cancer and septic shock. Platelets play an even more central part in clotting. Some clotting is good and prevents adverse events like uncontrolled bleeding. Other clotting can lead to stroke and death.

Ware said the crux of the problem is developing a drug that can shut off platelets in unhealthy clotting and inflammation without also turning off the important healthy functions of platelets.

Ion Channels and High Blood Pressure

Nancy Rusch, Ph.D., professor and chair of the Department of Pharmacology and Toxicology in the UAMS College of Medicine, and her research team are working to devise new therapies to lower blood pressure. They collaborate with other investigators in the Cardiovascular Center, including Sung Rhee, Ph.D., James Marsh, M.D., Sabine Telemaque, Ph.D., and Philip Palade, Ph.D., to identify ion channels in the cardiovascular system that regulate blood vessel diameter.

The goal is to develop drugs or small molecules that someone with high blood pressure could take to either block ion channels that elevate blood pressure through vessel constriction or activate channels that dilate blood vessels and thereby lower blood pressure.

Because people with high blood pressure often show no obvious negative health effects from the condition, it can be difficult to motivate them to take the sometimes multiple medications necessary to reduce hypertension, especially when many of those medications have side effects that may make them feel worse.

“The more drugs that must be taken, the less apt they are to take them,” Rusch said. “One of our goals is to develop a long-term therapy for hypertension in which a therapeutic ion channel gene could be expressed in blood vessels for months or years to normalize blood pressure as the ultimate form of compliance.”

Leading the Way

The Heart, Lung and Blood Institute of the National Institutes of Health awarded UAMS $4.41 million this fiscal year for heart and vascular research. Such funding is awarded to only the top 6 percent of grant applicants.

“You can’t be in the top 6 percent of the field and not be doing state-of-the-art work,” Ware said.

Several cardiovascular research efforts were highlighted at a university showcase in November. UAMS Cardiovascular Center faculty members were involved in many of the projects presented. Rusch and Ware also are on the center’s faculty.

“I think we’ve done a good job, particularly with the establishment of this Cardiovascular Center, of bringing folks together, especially in basic science,” Post said. “We all want to translate our research findings into patient care and have a clinical impact that improves the health of all Arkansans.”

In addition to the projects led by Post, Ware and Rusch, cardiovascular research efforts highlighted at the showcase included:

·         Can We Improve Kidney Function Prior to Kidney Transplant? Researchers: Lee Ann MacMillan-Crow, Nirmala Parajuli, Akira Marine.

·         Predicting Heart Attacks in Women: Recognizing Early Symptoms. Researchers: Jean McSweeney, Mario Cleves, Ellen Fischer, Martha Rojo, Christina Pettey.

·         LOX-1: A Novel Target for Cardiovascular Diseases. Researchers: Sadip Pant, Dayuan Li, Changping Hu, Jingjun Lu, Xianwei Wang, Zufeng Ding, Kottayil Varughese, Magomed Khaidakov, Jay Mehta.

·         Scaffolding of Potassium Channels in Cerebral Arteries and its Potential Implication for Stroke during Beta-Blocker Therapy. Researchers: Christopher Moore, Bhavya Chandrika, Piper Nelson, Mathew Steephan, Nancy Rusch, Sung Rhee.

·         Identification and Preclinical Evaluation of New Therapeutic Targets to Treat Sepsis-Induced Kidney Injury. Researchers: Joseph Holthoff, When Wang, Naeem Patil, Philip Mayeux.

·         Successful Microbubble Sonothrombolysis Without Tissue Plasminogen Activator in a Rabbit Model of Acute Ischemic Stroke. Researchers: William Culp, John Lowery, Aliza Brown, Leah Hennings, Paula Roberson, Jeff Hatton, Sean Woods, Rene Flores, Michael Borrelli.

·         Personalized Genomic Approaches to Enhance the Cardiovascular Health of Arkansans. Researchers: Ryan Farris, Charla Wiley, Elvin Price.

·         Biological Mechanisms and Potential Treatments of Radiation-Induced Heart Disease. Researchers: Marjan Boerma, Viji Mohanseenivasan, Preeti Tripathi, Ben Lieblong.

·         Upregulation of MicroRNAs 21 and 223 in an Animal Model of Pulmonary Hypertension. Researchers: Igor Gubrij, Amanda Pangle, Li Pang, Larry Johnson.

·         Weekend Admissions Predict Higher Mortality in Patients with Atrial Fibrillation — Nationwide Analysis. Researchers: Abhishek Deshmukh, Sadip Pant, Gagan Kumar, Zoran Bursac, Hakan Paydak, Jawahar Mehta.