,Glucagon-like peptide 1 reverses myocardial hypertrophy through cAMP/PKA/RhoA/ROCK2 signaling

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Myocardial hypertrophy is a major pathological and physiological process during heart failure.Glucagon-like peptide 1 (GLP-1) is a glucagon incretin hormone released from the gut endocrine L-cells that has protective effects on various cardiovascular diseases,including hypertension,atherosclerosis,and myocardial hypertrophy.However,the protective mechanisms of GLP-1 in myocardial hypertrophy remain unclear.Here,we showed that the GLP-1 agonist liraglutide and dipeptidyl peptidase 4 inhibitor alogliptin decreased heart weight and cardiac muscle cell volume in spontaneously hypertensive rats (SHR).In H9C2 cell hypertensive models induced by angiotensin Ⅱ,GLP-1 treatment reduced myocardial cell volume,inhibited the expressions of atrial natriuretic peptide,brain/B-type natriuretic peptide,β-myosin heavy chain,RhoA,and ROCK2,and decreased MLC and MYPT1 phosphorylation.When H9C2 cells were treated with H89,a PKA inhibitor,the inhibitory effect of GLP-1 disappeared,while the inhibitory role was enhanced under the treatment of Y-27632,a ROCK2 inhibitor.These results suggested that GLP-1 might reverse myocardial hypertrophy through the PKA/RhoA/ROCK2 signaling pathway.
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