Translational Medicine
Open Access
ISSN: 2161-1025
ISSN: 2161-1025
Sheng Wang
Guangdong Academy of Medical Sciences, China
Scientific Tracks Abstracts: Transl Med
Background: Protein kinase C (PKC)-�?µ activation is a mechanism of preconditioning cardio-protection, but its role in repeated noninvasive limb ischemic preconditioning (rNLIP) mediated cardio-protection against myocardial ischemia/reperfusion (I/R) injury in diabetes is unknown. Methods: Spragueâ�?�?Dawley rats were induced diabetes with streptozotocin and subjected to coronary artery occlusion and reperfusion in the absence or presence of rNLIP (three cycles of 5 minutes occlusion/5 minutes reperfusion) in a hind limb daily for three days prior to inducing I/R. In vitro, cardiac H9C2 cells were cultured with normal or high glucose for 48 hours and subjected to hypoxia/ re-oxygenation(H/R) with or without siRNAs of PKC-�?µ or signal transducers and activators of transcription 3(STAT3). Remote time hypoxia preconditioning (HPC) was achieved by three cycles of 5 minutes hypoxia followed by 5 minutes re-oxygenation 24 hours before inducing H/R. Results: In eight week diabetic rats, post-ischemic myocardial infarct size and troponin-I release were significantly higher with concomitant cardiac PKC-E overexpression, while the phosphorylation of cardioprotective proteins STAT3 (p-STAT3) and Akt (p-Akt) were lower compared to non-diabetic rats (all P<0.05). rNLIP reduced infarct size and post-ischemic troponin release in non-diabetic and diabetic rats and moderately but significantly reduced cardiac PKC-E expression and increased cardiac p-STAT3 and p-Akt. In H9C2 cells, high glucose increased PKC-E activation and exacerbated post-H/R injury, accompanied with reducing p-STAT3 and p-Akt, which were all reversed by HPC. The above HPC protective effects were abolished by either PKC-E or STAT3 gene-knockdown. Conclusion: rNLIP may attenuate diabetic heart I/R injury by mitigating high glucose induced PKC-E overexpression and subsequently activating STAT3.
Sheng Wang is the Chief of Department of Anesthesiology, Guangdong General Hospital, Guangzhou, China. He completed his MD in Anesthesiology from Peking Union Medical College in 2003, and was Master of Cardiac Anesthesia of International Heart School of Italy in Massa. He is now Vice President of Committee of Chinese Society of Cardiothoracic and Vascular Anesthesiology; member of Chinese Society of Anesthesiology (CSA) Youth Committee and member of committee of China Association of Anesthesiology (CAA).
Email: shengwang_gz@163.com