Research SPARCs a new kidney-heart connection
Karen Ocorr, Ph.D., assistant professor in the Development, Aging, and Regeneration Program, has devoted her research to understanding the basic cellular mechanisms that contribute to heart disease. People with heart disease have a high risk of developing kidney failure and vice versa, but the connections linking kidney failure and heart failure are not clear. In a new paper published in Circulation: Cardiovascular Genetics, her research team identified a protein called SPARC (secreted protein acidic and rich in cysteine) that helps explain how kidney disease might increase the risk of heart failure.
About 10% of adults in the US have kidney disease, a general term for progressive decline of kidney function, resulting from diabetes, lupus, hypertension, or certain congenital disorders. These patients face a greatly increased risk of heart failure, which is often fatal.
Kidneys play a vital role in human health — they remove waste (including drugs) from the blood, balance body fluids, control the production of red blood cells, and release hormones that regulate blood pressure.
Ocorr’s lab studies fruit flies, which are commonly used to decipher complex biological systems, even those of humans, because many of the genes involved are similar and they are easy to manipulate in the fly. She has developed a method to study details of heart function in flies. Working in her lab, Paul Hartley, Ph.D., senior lecturer in Functional Genetics at Bournemouth University in the UK, used this system to look at interactions between the fly “kidney” and heart function. Fruit flies don’t have human-like kidneys, but they do have cells that eliminate waste from the circulation.
In this study, Ocorr’s team examined heart function in mutant flies that lacked these kidney-like cells. Loss of kidney function caused a significant reduction in the ability of the heart to contract. Analysis of the flies’ “blood” showed greatly elevated levels of the protein SPARC, which likely contributed to the heart failure.
“The mutant flies allowed us to show that kidney function impacts heart function in the fly,” said Ocorr. “The effects were likely due to the accumulation of circulating factors such as SPARC.”
“This finding is important because, in humans, changes in SPARC levels are associated with cardiac aging, chronic inflammatory disease, and metabolic syndrome,” said Ocorr. “SPARC leads to accumulation of fibrous proteins in the extracellular matrix that stiffen tissues, which could account for the cardiac impairment.”
“If humans with kidney disease have increased levels of circulating SPARC, it could represent a new therapeutic target,” added Ocorr. “Treatments that remove SPARC from the blood or block its action might reduce heart damage.”
Ocorr and her collaborators are now examining whether deficiencies in cells that carry out the kidneys’ other task — regulating the amount of water removed in the filtration process — also impact heart function.
The paper is available online here.