Endogenous renin transcripts lacking exon 1 encode for a non secretory protein [exon(2–9)renin] that is synthesized in the cytosol and taken up by mitochondria. It was recently that cytosolic renin protects cardiac H9c2 cells from necrosis in vitro. In vivo, transcripts encoding for cytosolic renin are markedly upregulated in the rat heart after left ventricular ischemia.

Here we tested whether or not cardiac cells overexpressing exon(2–9)renin are protected against glucose depletion or an ischemic insult. In vitro investigations were performed with the exon(2–9)renin transfected H9c2 cells and the control lines H9c2 and pIRES which were cultured in the presence or absence of glucose. After 24 h rates of necrosis were determined by analyzing the LDH ratio (LDH release vs. LDH content). Ex vivo studies were performed with two transgenic rat lines (294 and 307) which express the transcript in various tissues including the heart. Hearts were isolated, retrogradely perfused in the Langendorff mode, and subjected to 30 min regional ischemia followed by 120 min reperfusion.

In vitro, depletion of glucose resulted in a significant increase of the rate of necrosis in control cells from 9.3 0.6% to 16.2 1.6% (p<0.05) whereas exon(2–9)renin transfected cells were protected from necrosis (7.8 1.1%; n. s. vs. controls). Furthermore, in the hearts of both transgenic lines, infarct size as percentage of the ischemic zone was reduced from 41.8 2.2% in control hearts to 24.7 3.8% (line 294) and 21.5 3.2% (line 307) respectively (both p<0.005 vs. control).

The data support the hypothesis that in contrast to secretory renin, the cytosolic renin protects cardiac cells from necrotic cell death induced by glucose depletion or ischemic stress and may therefore also be a target for a protection against an ischemia/reperfusion injury in the heart.