Hardened Arteries Have Leaky Tissue

Closing the gaps between cells that line patients’ arteries could be a new strategy to treat atherosclerosis, a condition that often leads to heart attacks and strokes (Sci. Transl. Med., DOI: 10.1126/scitranslmed.3002761). Increased permeability between arterial cells allows cholesterol and immune cells to accumulate in blood-vessel walls, leading to dangerous plaque formation. Using fluorescent dyes, engineered tissue, and aortas from mice, Cynthia A. Reinhart-King and coworkers at Cornell University showed that hardened arteries—those with stiff tissue scaffolding—cause cells embedded within them to increase their contractile forces and pull apart from one another. To prevent this cell contraction, the researchers focused on rho-associated kinase (ROCK), an enzyme that helps regulate cell forces and movement via structural proteins such as actin. By inhibiting ROCK with the small molecule Y-27632, Reinhart-King’s group decreased the average cell-cell gap in hardened synthetic tissue by about 2 µm. Whether ROCK itself is the best target for future therapeutics rather than other molecules further downstream in the ROCK signaling pathway remains to be seen, comments biological engineer Douglas A. Lauffenburger of MIT, but the results of this study are “enticing.”