An international team of scientists led by the National University of Singapore’s Cardiovascular Research Institute has discovered that chondroitin sulfates — a group of molecules normally found only in connective tissues — accumulate and cause inflammation in the hearts of patients with heart failure. The research is published in the journal Circulation.
Chondroitin sulfate (marked in red), virtually absent in healthy human heart tissue (left panel), is found to accumulate in hearts of patients with heart failure, forming dense molecular ‘nets’ around the heart muscle cells (right panel). Cell nuclei are marked in blue. Scale bar – 50 μm. Image credit: National University Heart Centre, Singapore.
Chondroitin sulfate is a form of polysaccharide, a long chain of sugar molecules usually attached to certain proteins, forming molecular ‘nets’ outside cells.
“In the rare disease known as mucopolysaccharidosis (MPS) type VI, patients have a genetic mutation that leads to systemic chondroitin sulfate accumulation,” said co-author Dr. Zhao Rong-Rong, from the National University of Singapore’s Cardiovascular Research Institute.
“Because of this, MPS IV patients end up with multi-organ failure, including irregular heartbeats, enlarged heart muscles which may eventually result in heart failure.”
“This evidence gives a very clear link between chondroitin sulfate accumulation and heart diseases.”
In the new study, Dr. Rong-Rong and co-authors studied changes in myocardial chondroitin sulfate in non-MPS failing hearts.
Failing human hearts, even from patients without MPS VI, displayed significant chondroitin sulfate accumulation, particularly in regions of intense fibrosis.
“Using the arylsulfatase B enzyme, an approved treatment for MPS VI, we demonstrated that fibrosis and disease progression can be effectively treated in an animal model of heart failure,” the researchers said.
“This new treatment approach could potentially add to current treatment strategies, which include long-established medicines such as beta-blockers and ACE-inhibitors.”
“There are more examples now that prove that understanding rare diseases gives us clues for how to treat common conditions,” said lead author Dr. Roger Foo, from the Department of Cardiology at the National University Heart Centre in Singapore.
“We have learnt that chondroitin sulfate molecular nets don’t only accumulate inside the heart muscle of patients with MPS VI.”
“Heart failure patients without MPS VI also have these molecular nets, which can be targeted with a medicine that is already U.S. FDA-approved.”
“Targeting these molecular nets may bring a fresh new treatment approach for patients with this severe debilitating disease.”
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Rong-Rong Zhao et al. Targeting Chondroitin Sulfate Glycosaminoglycans to Treat Cardiac Fibrosis in Pathological Remodeling. Circulation, published online January 25, 2018; doi: 10.1161/CIRCULATIONAHA.117.030353
