Source: Cincinnati Children’s Hospital Medical Center
Summary: Researchers used an experimental targeted molecular therapy to block a matrix-forming protein in heart cells damaged by heart attack, reducing levels of scarred muscle tissue and saving mouse models from heart failure.
Fibronectin is a high-molecular-weight glycoprotein and it helps form a cell-supporting matrix for the body’s connective tissues, aiding tissue repair after injury. But after a heart attack, fibronectin overreacts, it polymerizes and helps produce too much connective matrix. It also causes the hyperactive production of clogged and dysfunctional cardio myofibroblast cells that damage the heart. Researchers at the Cincinnati Children’s Heart Institute manufactured peptide called pUR4 to block the fibronectin protein in human heart cells donated by heart failure patients. The treatment prevented the human heart cells from failing and restored their function. The treatment also reduced fibrosis and improved heart function after a simulated heart attack in mice. The research findings were published in the journal Circulation.
The pUR4 molecular treatment used in the current study is one of several compounds the research team are testing that show promise in preliminary preclinical research data. A key question in the current study was verifying the results of pUR4 targeted molecular therapy in both the mouse models and human heart failure cells. In mice with simulated heart attack that as a control experiment received a placebo therapy, the animals developed significant fibrosis and heart failure. When researchers treated mice with pUR4 for just the first seven days after a heart attack, or genetically deleted fibronectin activity from the heart cells of mice, these reduced fibrosis and improved cardiac function. Treatment of human failing heart cells with pUR4 also reduced their fibrotic behavior.
More Information: Iñigo Valiente-Alandi et al, “Inhibiting Fibronectin Attenuates Fibrosis and Improves Cardiac Function in a Model of Heart Failure”, Circulation (2018). DOI: 10.1161/CIRCULATIONAHA.118.034609