Do the biological underpinnings of heart failure share more in common with cancerous tumors than other cardiovascular diseases?
Research presented at American Heart Association meeting may show why heart failure treatments fail.
A team of Medical University of South Carolina (MUSC) researchers and cardiologists are presenting a number of studies at the American Heart Association conference that point toward new treatments for heart failure patients.
According to the American Heart Association, more than 5 million Americans are living with heart failure, and 550,000 new cases are diagnosed each year. It is a chronic disease that has no cure and typically worsens rapidly.
Dr. Francis G. Spinale and several other researchers from MUSC have put together scientific clues resulting in more than a dozen research studies on patients and mice that strongly suggest that a family of proteins called matrix metalloprotienase (MMP) play a crucial role in why the supporting tissue surrounding the heart, called the myocardium, goes through significant and deleterious effects in heart failure patients.
The conclusions reached by the team have already led to the development of a blood test for these MMPs. But more significantly, according to MUSC cardiac specialist Francis G. Spinale, MD, PhD, this research may demonstrate why current treatments for heart failure are failing and point to novel treatment methods for heart failure patients, reduce the number of people on the heart transplant list and help prioritize those heart failure patients currently on the list.
Spinale said that this discovery dates back to the 1980s when he and colleagues observed microscopic changes and gross abnormalities in the tissues surrounding the hearts of patients with coronary artery disease. Naturally, Spinale wanted to know what caused these profound changes in these structures?
He found part of his answer in an unlikely place: an oncology conference.
"In early 90s I accidentally walked into a cancer conference and this oncologist was talking about how a tumor moves and invades normal tissue and he described these enzymes (later named MMPs) that chew and change the matrix of cell," he said.
"I put two and two together and theorized that these MMPs might play a role in some major cardiovascular diseases," he said.
Spinale and other researchers at MUSC then examined the hearts of transplant patients and discovered that these MMPs were significantly up regulated in heart failure patients. This was an observation that had eluded cardiologists for years because the number of MMPs in normal hearts is very low. Once heart disease sets in, there is a rapid and robust up regulation, he said.
"As a matter of fact, the MMPs in heart failure patients are very similar to those expressed in aggressive, malignant tumors which leads me to suspect that these MMPs are a pathologic group of enzymes that are expressed in disease progression in general," he said.
From these published discoveries, Spinale and his colleague, Dr. Michael Zile, developed a blood test to measure these MMPs in bloodstreams of patients so they could screen patients early in the disease. This allowed MUSC cardiologists to predict the progression of the disease and demonstrate a different signature of these MMPS in patients with different types of heart failure and guide us to a more personalized form of treatment.
"Indeed, we showed a very different MMPs profile exists in high blood pressure and heart failure than those patients with just a heart attack and heart failure," he said. We also assumed that in other cardiovascular diseases the MMP profiles would be different too. In fact, in thoracic aortic aneurysms, different MMPS emerge in the aortic wall and contribute to this disease."