Apolipoprotein J/Clusterin Is Induced in Vascular Smooth Muscle Cells After Vascular Injury

Abstract

Background-Understanding the precise molecular mechanisms underlying the phenomenon of restenosis after PTCA may help us to develop a new strategy for the treatment of restenosis after PTCA. The purpose of this study was to identify the genes involved in vascular restenosis. Methods and Results-Applying a differential hybridization method to a model of the balloon-injured rabbit aorta, we identified 6 cDNA clones that were upregulated after injury. Northern blot showed that 5 genes, but not apolipoprotein J (apoJ)/clusterin, were constitutively expressed in noninjured aorta and upregulated after balloon injury. ApoJ mRNA was not detectable in noninjured aorta (control), began to be expressed at 6 hours after injury, showed a peak level at 24 hours (a 48-fold increase), gradually declined, and returned to the control level at 24 weeks. Western blot and immunohistochemistry demonstrated no expression of apoJ protein in noninjured aorta, an expression of apoJ at 2 days after balloon injury, and a peak level (a 55-fold increase) at 2 to 8 weeks. The expression of apoJ protein continued until 24 weeks after injury. In situ hybridization revealed that apoJ mRNA was expressed in smooth muscle cells (SMCs) of media at 2 days after injury and in SMCs of media and neointima at 2 weeks. To analyze the function of apoJ, stably transfected rabbit SMCs were created. The expression of apoJ stimulated proliferation and migration of SMCs. Conclusions-ApoJ is dramatically induced in media and neointima after vascular injury, suggesting that apoJ contributes to restenosis after angioplasty.

Clusterin plays an important role in hepatocellular carcinoma metastasis

“…Apart from modulating apoptosis, CLU has been implicated in tissue remodeling processes. For instance, CLU was dramatically induced in vascular smooth muscle cells (VSMC) after vascular injury (Miyata et al, 2001). Also, expression of clusterin in VSMC induced migration and nodule formation (Millis et al, 2001).…”

Waon Therapy Upregulates Hsp90 and Leads to Angiogenesis Through the Akt-Endothelial Nitric Oxide Synthase Pathway in Mouse Hindlimb Ischemia

“…25 Briefly, 10-μg protein samples were resuspended in a reduced sample buffer, and then electrophoresed on a 4-12% Bis-Tris gel (Novex, San Diego, CA, USA) with MOPS running buffer, blotted to nitrocellulose, and sequentially probed with polyclonal rabbit antisera raised against Hsp90, Hsp70, Hsp60, Hsp32, Hsp27, Akt, phosphorylated-Akt (pAkt), eNOS, phosphorylated-eNOS (p-eNOS) or actin (Santa Cruz Biotechnology, Santa Cruz, CA, USA). A horseradish peroxidase-conjugated goat anti-rabbit antibody (Santa Cruz Biotechnology, Santa Cruz, CA, USA) was then added, and secondary antibodies were detected through autoradiography using enhanced chemiluminescence (GE Healthcare UK Ltd, Little Chalfont, UK).…”

Dietary oil modifies the plasma proteome during aging in the rat

“…The protein has been reportedly implicated in diverse physiological processes such as lipid transport (Rosenberg and Silkensen 1995), complement inhibition, tissue remodeling, membrane recycling, cell-cell and cellsubstratum interactions (Silkensen et al 1994), stabilization of stressed proteins in a foldingcompetent state (Trougakos and Gonos 2004), and promotion or inhibition of apoptosis . In human plasma, Apo J is associated with Apo A-I in high-and very high-density lipoproteins (Jenne et al 1991), and its expression stimulates the proliferation and migration of smooth muscle cells (Miyata et al 2001). In vivo, Apo J/ clusterin is up-regulated in many severe physiological disturbances, including accumulation in the artery wall during the development of atherosclerosis .…”