Upregulation of GRP78 and caspase-12 in diastolic failing heart.

Abstract

The endoplasmic reticulum (ER) fulfills multiple cellular functions. Various stimuli can potentially cause ER stress (ERS). ERS is one of the intrinsic apoptosis pathways and apoptosis plays a critical role in hypertension. Glucose regulated protein 78 (GRP78) has been widely used as a marker for ERS and caspase-12 mediated apoptosis was a specific apoptotic pathway of ER. The expression of GRP78 and caspase-12 remains poorly understood in the diastolic heart failure resulting from hypertension. We used spontaneously hypertensive rats (SHRs) to establish a model of diastolic heart failure, and performed immunohistochemistry, western blot, and real-time PCR to analyze GRP78 and caspase-12. We found that GRP78 and caspase-12 had enhanced expression at protein and mRNA levels. These results suggest that GRP78 and caspase-12 were upregulated in cardiomyocytes and ERS can contribute to cardiac myocyte apoptosis in the diastolic heart failure resulting from hypertension.