Dihydro-artemisinin inhibits angiotensin II-induced cardiac fibroblasts proliferation and induces apoptosis through phosphoinositide 3-kinase/akt pathway

Abstract

Cardiac fibroblasts (CFs) abnormal proliferation can trigger myocardial fibrosis, which is closely related to a variety of cardiovascular diseases. This study investigated the effect of dihydroartemisinin (DHA) on CF growth through PI3K/AKT with angiotensin II (AngII). CCK-8 method and EdU were used detect cell proliferation, and flow cytometry assessed apoptosis of CFs. The PI3K and AKT expressions were determined, whilst immunofluorescence staining and RT-qPCR measured α-smooth muscle actin (α-SMA) level. With rat CFs exhibiting typical fibroblast morphology and nuclei in spindle, oval or polygonal shape, these cells were positive for the fibroblast marker vimentin. Treatment with AngII resulted in increased proliferation of CFs, but the proliferation declined in the presence of DHA (p < 0.05). Meanwhile, the AngII group had lower apoptosis of CFs than blank and DHA groups with highest apoptosis observed in the DHA group. α-SMA increased at the mRNA and protein levels after Ang II treatment and decreased after DHA treatment (p < 0.05). Importantly, the Ang II upregulated PI3K and AKT in CFs (p < 0.05) and the increase was abrogated by DHA administration with lowest levels (p < 0.05). Ang II activates PI3K/Akt in normal CFs, as administration of DHA can inhibit the effect of Ang II, thereby inhibiting proliferation of CFs induced by AngII and inducing apoptosis.