Role of PI3K/Akt signaling pathway in cardiac fibrosis

Heart failure (HF) is considered as a severe health problem worldwide, while cardiac fibrosis is one of the main driving factors for the progress of HF. Cardiac fibrosis was characterized by changes in cardiomyocytes, cardiac fibroblasts, ratio of collagen (COL) I/III, and the excessive production and deposition of extracellular matrix (ECM), thus forming a scar tissue, which leads to pathological process of cardiac structural changes and systolic as well as diastolic dysfunction. Cardiac fibrosis is a common pathological change of many advanced cardiovascular diseases including ischemic heart disease, hypertension, and HF. Accumulated studies have proven that phosphoinositol-3 kinase (PI3K)/Akt signaling pathway is involved in regulating the occurrence, progression and pathological formation of cardiac fibrosis via regulating cell survival, apoptosis, growth, cardiac contractility and even the transcription of related genes through a series of molecules including mammalian target of rapamycin (mTOR), glycogen synthase kinase 3 (GSK-3), forkhead box proteins O1/3 (FoxO1/3), and nitric oxide synthase (NOS). Thus, the review focuses on the role of PI3K/Akt signaling pathway in the cardiac fibrosis. The information reviewed here should be significant in understanding the role of PI3K/Akt in cardiac fibrosis and contribute to the design of further studies related to PI3K/Akt and the cardiac fibrotic response, as well as sought to shed light on a potential treatment for cardiac fibrosis.