Estrogenic modulation of lysyl oxidase in adult cardiac fibroblasts

Abstract

Lysyl oxidase (LOX) is necessary for the biosynthesis of functional collagen through its crosslinking of collagen and elastin. Increased LOX expression has been associated with hepatic, lung and kidney fibrosis, but the role of LOX in the heart is not known. Cardiac fibroblasts constitutively express pro‐LOX protein and bone morphogenic protein‐1, which cleaves pro‐LOX to generate active LOX and LOX‐propeptide. We hypothesized that LOX expression and activity in the heart is regulated by estrogen and may contribute to gender specific cardioprotection by altering collagen processing. Adult cardiac fibroblasts were isolated from ovariectomized (OX) and intact female rats. Cells were grown in media with 10% FBS, and serum starved prior to treatment with 17β‐estradiol. Fibroblasts from OX rats had the highest basal expression of pro‐LOX (200% vs. intact), which was suppressed by estrogen. In contrast, estrogen enhanced pro‐ and active LOX expression in fibroblasts from intact females. These findings indicate that changes in hormonal status alter cardiac fibroblast expression of pro‐form and active LOX. Future studies are warranted to evaluate the estrogenic modulation of LOX expression and activity in the heart, as well as the resulting effects on myocardial collagen and cardiac function.