Cathepsin S Activity Controls Injury-Related Vascular Repair in Mice via the TLR2-Mediated p38MAPK and PI3K−Akt/p-HDAC6 Signaling Pathway

• DOI: 10.1161/atvbaha.115.307110
• Publication Date: 2016-07-01T00:50:21Z
• Authors: Hongxian Wu; Xian Wu Cheng; Lina Hu; Kyosuke Takeshita; Chen Hu; Qiuna Du; Xiang Li; Enbo Zhu; Zhe Huang; Maimaiti Yisireyili; Guangxian Zhao; Limei Piao; Aiko Inoue; Haiying Jiang; Yanna Lei; Xiaohong Zhang; Shaowen Liu; Qiuyan Dai; Masafumi Kuzuya; Guo-Ping Shi; Toyoaki Murohara
• Keywords: Male; 0301 basic medicine; Genotype; Carotid Artery, Common; vascular remodeling; Myocytes, Smooth Muscle; Histone Deacetylase 6; Histone Deacetylases; Muscle, Smooth, Vascular; 03 medical and health sciences; Cell Movement; 615; Neointima; Animals; neointimal formation; Cells, Cultured; Cell Proliferation; Mice, Knockout; Basic Sciences; Cell Cycle Checkpoints; HDAC6; Cathepsins; 3. Good health; Histone Deacetylase Inhibitors; Disease Models, Animal; Phenotype; cathepsin S; Phosphatidylinositol 3-Kinase; Carotid Artery Injuries

Objective— Cathepsin S (CatS) participates in atherogenesis through several putative mechanisms. The ability of cathepsins to modify histone tail is likely contribute stem cell development. Histone deacetylase 6 (HDAC6) required modulating the proliferation and migration various types cancer cells. Here, we investigated cross talk between CatS HADC6 injury-related vascular repair mice. Approach Results— Ligation injury carotid artery mice increased expression, CatS-deficient showed reduced neointimal formation injured arteries. deficiency decreased phosphorylation levels p38 mitogen-activated protein kinase, Akt, HDAC6 toll-like receptor 2 expression ligated genetic or pharmacological inhibition also alleviated induced by platelet-derived growth factor BB cultured smooth muscle cells (VSMCs), kinase Akt phospho-HDAC6 levels. Moreover, caused decrease activity VSMCs response BB. inhibitor tubastatin A downregulated factor–induced VSMC migration, whereas overexpression exerted opposite effect. Tubastatin intimal hyperplasia injury. Toll-like silencing proliferation. Conclusions— This first report detailing cross-interaction 2–mediated during repair. These data suggest that CatS/HDAC6 could be a potential therapeutic target for control diseases are involved lesion formation.