Epigallocatechin gallate (EGCG), a bioactive ingredient of green tea, plays a 
protective role in the cardiovascular system. Homocysteine (Hcy) is a major risk 
factor for chronic kidney disease and cardiovascular disease. The present study 
aimed to investigate the role of EGCG in Hcy-induced proliferation of vascular 
smooth muscle cells (VSMCs) and its underlying mechanism. We also explored the 
roles of rennin-angiotensin system (RAS), extracellular signal-regulated kinases 
(ERK1/2), and p38 mitogen-activated protein kinase (p38 MAPK) in this process. 
Human aortic smooth muscle cells (HASMCs) were treated with different drugs for 
different periods. The proliferation rate of HASMCs was detected using the CCK-8 
and BrdU labeling assays. The Western blot assay was used to determine the 
expression levels of angiotensin II type 1 receptor (AT-1R), ERK1/2, and p38 
MAPK. Compared with the control group, the HASMCs treated with Hcy at different 
doses (100, 200, 500, and 1000 µM) showed significantly increased proliferation. 
Hcy increased the expression of AT-1R, whereas EGCG decreased the protein 
expression of AT-1R. Furthermore, we found that Hcy-induced expression of 
p-ERK1/2 and p-p38MAPK was dependent on AT-1R. Compared with Hcy 
(500 µM)-treated cells, EGCG (20 µM)-treated cells showed decreased 
proliferation as well as expression of AT-1R, p-ERK1/2, and p-p38MAPK. In 
addition, HASMC proliferation was suppressed by the addition of an AT-1R blocker 
(olmesartan), an ERK1/2 inhibitor (PD98059), and a p38MAPK inhibitor (SB202190). 
EGCG can inhibit AT-1R and affect ERK1/2 and p38MAPK signaling pathways, 
resulting in the decrease of VSMC proliferation induced by Hcy.