Tissue plasminogen activator (t-PA), a protease released by vascular endothelial cells, keeps blood flowing freely by busting up clots. But t-PA is also produced by sympathetic nerve endings where, according to Schaefer et al. on page 2191, it enhances the release of norepinephrine (NE), which can cause the heart to beat erratically.
The clot-busting power of t-PA—which works by cleaving the proenzyme plasminogen into the active plasmin that then breaks down the clot protein fibrin—is often used to dissolve clots in patients who have had heart attacks or strokes. But treatment with recombinant t-PA has been associated with erratic heartbeats (or arrhythmias)—a common cause of death post–heart attack.
The team now shows that the production of t-PA causes sympathetic nerve endings in the heart to release NE. And NE, which constricts vessels and increases heart rate, is known to trigger arrhythmias. Indeed, mice lacking...
