Allicin attenuates pathological cardiac hypertrophy by inhibiting autophagy via activation of PI3K/Akt/mTOR and MAPK/ERK/mTOR signaling pathways.
BACKGROUND
Cardiac hypertrophy is an adaptive response of the myocardium to pressure or volume overload. Recent evidences indicate that allicin can prevent cardiac hypertrophy. However, it is not clear whether allicin alleviates cardiac hypertrophy by inhibiting autophagy.


PURPOSE
We aimed to investigate the effects of allicin on pressure overload-induced cardiac hypertrophy, and further to clarify the related mechanism.


STUDY DESIGN/METHODS
Cardiac hypertrophy was successfully established by abdominal aortic constriction (AAC) in rats, and cardiomyocytes hypertrophy was simulated by angiotensin II (Ang II) in vitro. Hemodynamic parameters were monitored by organism function experiment system in vivo. The changes of cell surface area were observed using HE and immunofluorescence staining in vivoand in vitro, respectively. The expressions of cardiac hypertrophy relative protein (BNP and β-MHC), autophagy marker protein (LC3-II and Beclin-1), Akt, PI3K and ERK were detected by western blot.


RESULTS
Allicin could improve cardiac function, and reduce cardiomyocytes size, and decrease BNP and β-MHC protein expressions. Further results showed that allicin could lower LC3-II and Beclin-1 protein expressions both in vivo and in vitro experiments. And pharmacological inhibitor of mTOR, rapamycin could antagonize the effects of allicin on Ang II-induced cardiac hypertrophy and autophagy. Simultaneously, allicin could promote the expressions of p-Akt, p-PI3K and p-ERK protein.


CONCLUSION
These findings reveal a novel mechanism of allicin attenuating cardiac hypertrophy which allicin could inhibit excessive autophagy via activating PI3K/Akt/mTOR and MAPK/ERK/mTOR signaling pathways.
['Ba|Lina|L|', 'Gao|Jingquan|J|', 'Chen|Yunping|Y|', 'Qi|Hanping|H|', 'Dong|Chonghui|C|', 'Pan|Hao|H|', 'Zhang|Qianhui|Q|', 'Shi|Pilong|P|', 'Song|Chao|C|', 'Guan|Xueying|X|', 'Cao|Yonggang|Y|', 'Sun|Hongli|H|']
D000804:Angiotensin II D000818:Animals D001343:Autophagy D006332:Cardiomegaly D002316:Cardiotonic Agents D004220:Disulfides D020935:MAP Kinase Signaling System D008297:Male D032383:Myocytes, Cardiac D019869:Phosphatidylinositol 3-Kinases D051057:Proto-Oncogene Proteins c-akt D017208:Rats, Wistar D015398:Signal Transduction D013441:Sulfinic Acids D058570:TOR Serine-Threonine Kinases
Allicin Cardiac hypertrophy Autophagy PI3K/Akt mTOR MAPK/ERK