Cathepsin K (catK) is a potent lysosomal
cysteine protease involved in extracellular matrix (ECM) degradation and inflammatory remodeling responses. Here we have investigated the contribution of catK deficiency on carotid arterial remodeling in response to flow cessation in
apoE-/- and wild type (wt) background.
Ligation-induced
hyperplasia is considerably aggravated in
apoE-/- versus wt mice. CatK
protein expression was significantly increased in neointimal lesions of
apoE-/- compared with wt mice, suggesting a role for catK in intimal
hyperplasia under hyperlipidemic conditions. Surprisingly, CatK deficiency completely blunted the augmented hyperplastic response to flow cessation in
apoE-/-, whereas
vascular remodeling in wt mice was unaffected. As catK deficiency did neither alter lesion
collagen content and elastic laminae fragmentation in vivo, we focused on effects of catK on (systemic) inflammatory responses. CatK deficiency significantly reduced circulating CD3 T-cell numbers, but increased the regulatory T cell subset in
apoE-/- but not wt mice. Moreover, catK deficiency changed CD11b+Ly6G-Ly6C high monocyte distribution in
apoE-/- but not wt mice and tended to favour macrophage M2a polarization. In conclusion, catK deficiency almost completely blunted the increased
vascular remodeling response of
apoE-/- mice to flow cessation, possibly by correcting
hyperlipidemia-associated pro-inflammatory effects on the peripheral immune response.