The cryoprotectant trehalose could inhibit ERS-induced apoptosis by activating autophagy in cryoprotected rat valves

Hongyan Wu,Qing Chang

doi:10.1371/journal.pone.0194078

Abstract

Valvular diseases are common health problems that are strongly related to high morbidity and mortality; aortic valve allograft transplantation may be a promising way to improve survival and relieve symptoms. However, ideal tissue viability has not been observed with common valve cryopreservation methods, which could lead to apoptosis and necrosis in cryopreserved tissue. It has been observed that trehalose plays a positive role by acting to maintain cell structures and protect cells from stress responses. In this study, we studied the effects of trehalose in protecting rat valve tissue from the cooling process. We found improved higher cell function in rat valves treated with trehalose during cryopreservation than in those treated with dimethyl sulphoxide (DMSO). To further explore the mechanisms, we found that trehalose could down-regulate the expression of cleaved caspase-3, an important molecule involved in cell apoptosis. In addition, treatment with trehalose also decreased Glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP), the key proteins in the endoplasmic reticulum stress (ERS) process. Intriguingly, we observed that trehalose promotes cryoprotected rat valve cell autophagy via an mTOR-independent but p38 MAPK-dependent signaling pathway. Additionally, miR-221 and miR-32 have been implicated in such cell activities. In summary, our study offers a new and meaningful cryopreservation approach for valve allograft storage.

Highlights

Congenital and acquired valvular diseases are worldwide problems with high morbidity and mortality
The group with 0.10 mol/L trehalose had the highest carbohydrate metabolism level (Fig 1C) and the lowest MDA level (Fig 1D) compared with other groups at 16 weeks. These results indicated that trehalose and dimethyl sulphoxide (DMSO) had almost the same cryopreservation effect in short-time groups, while trehalose performed better in the long term with an optimum concentration of 0.1 mol/L
These results indicated that trehalose might down-regulate apoptosis in cryoprotected valve cells via endoplasmic reticulum stress (ERS) signaling

Summary

Introduction

Congenital and acquired valvular diseases are worldwide problems with high morbidity and mortality. A wide range of common valvular diseases includes rheumatic heart disease, Takayasu arteritis, infective endocarditis and Marfan syndrome [1]. With the development of transplantation technology, cardiac centers decided to treat allografts with antibiotics and cryopreserve them at low temperature in order to prolong their. Function and mechanism of trehalose in cryoprotected rat valves life span [3]. These operations obviously decrease allograft durability and activity and are likely related to some complicated stress process that compromises apoptosis, the endoplasmic reticulum or autophagy [4]. Finding effective cryopreservation methods for valve allografts is of remarkable interest

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