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Mimicking the biological function of the extracellular matrix is an approach to developing cell adhesive biomaterials. The RGD peptide, derived from fibronectin (Fn), mainly binds to integrin αvβ3 and has been widely used as a cell adhesive peptide on various biomaterials. However, cell adhesion to Fn is thought to be mediated by several integrin subtypes and syndecans. In this study, we synthesized an RGD-containing peptide (FIB1) and four integrin α4β1-binding-related motif-containing peptides (LDV, IDAPS, KLDAPT, and PRARI) and constructed peptide-chitosan matrices. The FIB1-chitosan matrix promoted human dermal fibroblast (HDF) attachment, and the C-terminal elongated PRARI (ePRARI-C)-conjugated chitosan matrix significantly promoted HDF attachment through integrin α4β1 and syndecan binding. Next, we constructed a mixed ePRARI-C- and FIB1-chitosan matrix to develop a Fn mimetic biomaterial. The mixed ePRARI-C/FIB1-chitosan matrix promoted significantly better cell attachment and neurite outgrowth compared to those of either ePRARI-C- or FIB1-chitosan matrices. HDF adhesion to the ePRARI-C/FIB1-chitosan matrix was mediated by integrin, α4β1, α5β1, and αvβ3, similar to HDF adhesion to Fn. These data suggest that an ePRARI-C/FIB1-chitosan matrix can be used as a tool to analyze the multiple functions of Fn and can serve as a Fn-mimetic biomaterial.

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Background: L-carnitine is an essential nutrient that plays a vital role in fatty acid energy metabolism of the heart and skeletal muscles. Primary or secondary carnitine insufficiency contributes to progressive left ventricular systolic dysfunction and physical frailty. However, the clinical features of patients with heart failure with preserved ejection fraction (HFpEF) and carnitine insufficiency remain unclear. Objectives: The present study aimed to evaluate the clinical characteristics and outcomes of these patients. Design: A prospective cohort study. Setting: Tottori University hospital. Participants: 117 patients who were hospitalized with HFpEF (ejection fraction ≥45%). Measurement: All measurements were obtained at hospital discharge. Carnitine insufficiency was defined as the lowest quantile of free carnitine level (<56.3 μmol/L) or the highest quantile of acylcarnitine to free carnitine ratio (≥0.35). Nutritional status and physical activity were assessed by the Geriatric Nutritional Risk Index (GNRI) and Barthel index (BI). Left ventricular diastolic function was assessed by echocardiography. The composite endpoints were hospitalization for heart failure and death from cardiac causes. Results: Patients with carnitine insufficiency (44.4%) had lower values of GNRI and BI, higher B-type natriuretic peptide levels, and lower early diastolic mitral annular velocity in the subgroups with sinus rhythm compared with those with preserved carnitine (all p<0.05). During a mean follow-up of 472±249 days, composite endpoints occurred in 26.5% of patients. Multivariate Cox hazard analysis showed that carnitine insufficiency was an independent predictor of cardiac events (p<0.05). Conclusions: Carnitine insufficiency is associated with adverse outcomes in patients with HFpEF.