OBJECTIVE Cyclosporin A (CsA) is an immunosuppressant commonly used to prevent organ rejection but is associated with hyperlipidemia and an increased risk of cardiovascular disease. Although studies suggest that CsA-induced hyperlipidemia is mediated by inhibition of low-density lipoprotein receptor (LDLr)-mediated lipoprotein clearance, the data supporting this are inconclusive. We therefore s...

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with familial autosomal dominant hypercholesterolemia and is a natural inhibitor of the LDL receptor (LDLr). PCSK9 is degraded by other proprotein convertases: PC5/6A and furin. Both PCSK9 and the LDLr are up-regulated by the hypocholesterolemic statins. Thus, inhibitors or repressors of PCSK9 should amplify their beneficial ef...

The immunocytochemical development of the thoracolumbar sympathetic ganglion and its adrenal counterpart was studied in the chick from days 3.5 to 12 of incubation, using antibodies to 17 separate antigens, including antibodies to pan-neuroendocrine markers, catecholamine-synthesizing and proprotein-processing enzymes, and neuropeptides. Some of the antigens studied (Go protein-alpha subunit, t...

Alirocumab and evolocumab are monoclonal antibodies that block proprotein convertase subtilisin/kexin type 9 (PCSK9), a circulating protein that degrades low-density lipoprotein (LDL) receptors. These therapies increase LDL receptors on the cell surface and reduce plasma LDL cholesterol. Both therapies are approved to lower LDL cholesterol, a causative agent for atherosclerotic cardiovascular d...

The spread of cardiovascular diseases has the nature an epidemic, which is enhanced by lipid profile disorders, manifested hypercholesterolemia. Numerous conventional pharmacological tools for lowering cholesterol associated with low density lipoproteins do not make it possible to achieve target values in various categories patients. Inhibition proprotein convertase subtilisin/ kexin type 9 (PC...

Many secretory proteins and peptides are synthesized as inactive precursors that in addition to signal peptide cleavage undergo post-translational processing to become biologically active polypeptides. Precursors are usually cleaved at sites composed of single or paired basic amino acid residues by members of the subtilisin/kexin-like proprotein convertase (PC) family. In mammals, seven members...

Proprotein convertases are serine endoproteases implicated in the proteolytic processing of a large variety of regulatory proteins. An important role of proprotein convertases in tumorigenic processes has been suggested by various studies. In this study, the role of the proprotein convertase furin in PLAG1 proto-oncogene-induced salivary gland tumorigenesis was investigated. PLAG1 overexpressio...

Proprotein convertases are enzymes that proteolytically cleave protein precursors in the secretory pathway to yield functional proteins. Seven mammalian subtilisin/Kex2p-like proprotein convertases have been identified: furin, PC1, PC2, PC4, PACE4, PC5 and PC7. The binding pockets of all seven proprotein convertases are evolutionarily conserved and highly similar. Among the seven proprotein con...