Abstract
Aims: To evaluate the protective effects of exogenous pancreatic kallikrein (PKK) treatment on diabetic cardiomyopathy (DCM) and explore the underlying mechanisms.Methods and Results: Streptozotocin (STZ)-induced diabetic rats, a type 1 diabetic model, were treated with either PKK or saline for 12 weeks. Non-diabetic rats were used as controls. PKK administration attenuated the mitochondria swelling, Z line misalignments, myofibrosis and interstitial collagen accumulation in diabetic myocardial tissue. The oxidative stress imbalance including increased nitrotyrosine, decreased anti-oxidative components such as nuclear receptor nuclear factor like 2 (Nrf2), glutathione peroxidase 1(GPx-1), catalase (CAT) and superoxide dismutase (SOD), were recovered in the heart of PKK-treated diabetic rats. In diabetic rats, protein expression of TGF-β1 and accumulation of collagen I in the heart tissues was decreased after PKK administration. Markers for inflammation were decreased in diabetic rats by PKK treatment. Compared to diabetic rats, PKK reversed the degradation of IκB-α, an inhibitive element of heterotrimer nuclear factor kappa B (NF-κB). The endothelial nitric oxide synthase (eNOS) protein and myocardial nitrate/nitrite were impaired in the heart of diabetic rats, which, however, were restored after PKK treatment. The sarcoplasmic reticulum Ca2+-ATPase 2 (SERCA2) and phospholamban (PLN) were mishandled in diabetic rats, while were rectified in PKK-treated diabetic rats. The plasma NT-proBNP level was increased in diabetic rats while was reduced with PKK treatment.Conclusion: PKK protects against DCM via reducing fibrosis, inflammation, and oxidative stress, promoting nitric oxide production, as well as restoring the function of the calcium channel.
Highlights
Diabetic cardiomyopathy (DCM) was first introduced by Rubler et al (1972), who presented autopsy data from four diabetic patients
pancreatic kallikrein (PKK) protects against DCM via reducing fibrosis, inflammation, and oxidative stress, promoting nitric oxide production, as well as restoring the function of the calcium channel
Exogenous PKK had no effect on the blood glucose, serum lipids, body weight, and blood pressures in STZ-induced diabetic rats (Table 2)
Summary
Diabetic cardiomyopathy (DCM) was first introduced by Rubler et al (1972), who presented autopsy data from four diabetic patients. DCM is a main pathogenic factor for heart failure in diabetic patients (Kannel et al, 1974; Devereux et al, 2000). Among patients with DCM, the cumulative probability of death was 18%, and development of heart failure was 22% (Kain and Halade, 2017). Therapy for patients with diabetes focuses largely on glucose control. Before the onset of heart failure symptoms, patients lack enough standard treatments (Sung et al, 2015; Kain and Halade, 2017). There remains a significant incidence of cardiovascular disease even in optimally treated diabetic patients (Tate et al, 2017). More effective strategies are required to target DCM
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
