Interstitial fibrosis plays a key role in the development and progression of heart failure. Here,
we show that an enzyme that crosslinks collagen—Lysyl oxidase-like 2 (Loxl2)—is essential
for interstitial fibrosis and mechanical dysfunction of pathologically stressed hearts. In mice,
cardiac stress activates fibroblasts to express and secrete Loxl2 into the interstitium,
triggering fibrosis, systolic and diastolic dysfunction of stressed hearts. Antibody-mediated
inhibition or genetic disruption of Loxl2 greatly reduces stress-induced cardiac fibrosis and …