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Preventive Effects of Thermosensitive Biopolymer‐Conjugated C‐Peptide against High Glucose‐Induced Endothelial Cell Dysfunction
Author(s) -
Jung SeHui,
Lee JeeYeon,
Lee SeongHyeon,
Kwon MiHye,
Han EunTaek,
Park Won Sun,
Hong SeokHo,
Kim YoungMyeong,
Ha KwonSoo
Publication year - 2019
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201900129
Subject(s) - peptide , chemistry , biochemistry , conjugate , endothelial stem cell , elastin , biophysics , medicine , biology , in vitro , mathematical analysis , mathematics , pathology
C‐peptide has emerged as a potential drug for treating diabetic complications. However, clinical application of C‐peptide is limited by its short half‐life during circulation and costly synthesis methods. To overcome these limitations, a biocompatible and thermosensitive biopolymer‐C‐peptide conjugate composed of human C‐peptide genetically conjugated at the C‐terminus of nine repeats of lysine‐containing elastin‐like polypeptide (K9‐C‐peptide) is generated. K9‐C‐peptide exhibits reversible thermal phase behavior with a transition temperature dependent on polypeptide concentration. Degradation of K9‐C‐peptide hydrogel depends on the concentration of four cleavage enzymes as well as the reaction time and frequency of treatments with elastase‐2. The preventive effect of K9‐C‐peptide against high glucose‐induced human aortic endothelial cell dysfunction is further investigated. K9‐C‐peptide inhibits high glucose‐induced intracellular reactive oxygen species generation, transglutaminase 2 activation, and apoptosis, similar to the inhibitory effects of human C‐peptide. Thus, K9‐C‐peptide is a potential drug depot for the sustained delivery of C‐peptide to treat diabetic complications.