ABSTRACT
Aim To investigate the role of mechano- sensitive ion channel Piezol in regulating electrical re-modeling of atrial myocytes induced by hypertension and to further explore the potential mechanisms.Methods Spontaneously hypertensive rats ( SHR ) aged 30 - 32 weeks treated with or without valsartan (30 mg • kg 1 • d 1 ) were used.Wistar rats were used as control.Western blot was used to detect the protein expression of Piezol , Src and Cavl.2 in atrial appendages of rats and in atrial myocytes ( HL-1 cells) exposed to different levels of high hydrostatic pressure (20 and 40 mmHg) , Piezol inhibitor (GsmTx4) and agonist ( Yodal ) in vitro.Whole-cell patch clamp technique was employed to detect L-tvpe calcium current (ICa, ) and action potential duration ( APD) of atrial myocytes.Results Compared with Wistar rats in control group, the protein expressions of Piezol and Src significantly increased and the expression of Cavl.2 decreased in SHR group (P < 0.05 ), while the a- bove changes could he reversed in SHR treated with valsartan( P < 0.05 ) .Meanwhile, higher hydrostatic pressure (40 mniHg) could increase the expressions of Piezol and Src in HL-1 cells( P <0.05) and decrease the protein expression of Cavl.2 (P <0.05 ) , accompanied by a shortened APD and a decreased ICa,.GsmTx4 could significantly reverse the above changes.In addition, Piezol agonist Yodal could simulate electrical remodeling and related signal molecule changes in atrial myocytes induced by the high hydrostatic pressure.Conclusions Mechanosensitive ion channel Piezol participates in electrical remodeling induced by hypertension via activating Src kinase signaling pathway and then leading to the decrease of ICa ,.
ABSTRACT
Aim To investigate the mechanism of Pi- ezol in the phenotypic changes of rat coronary arterial smooth muscle cells ( CASMCs) induced by high hydrostatic pressure.Methods CASMCs were isolated from Wistar rats and stimulated for 24 h at 0, 120 and 180 mmHg, respectively.The expressions of Piezol , contractile phenotvpe-related proteins including Cavl.2 ,SM-MHC ,cx-SMA and synthetic phenotvpe-re- lated proteins including OPN , MMP-2, Coll al were detected by Western blot.The effect of calcium influx mediated by Piezol was detected by Laser confocal mi- j j croscopy.CASMCs were treated with Piezol agonist Yodal , inhibitor GsMTx4 and Piezol-siHNA , respectively and the expressions of contractile phenotvpe and synthetic phenotvpe-related proteins were detected by Western blot.Results Compared with control ( 0 mmHg) , the expressions of Piezol , OPN, MMP-2 and Collal increased, but the expressions of Cavl.2,SM- MHC and cx-SMA decreased in 120 mmHg as well as 180 mmHg group.After stimulated by 180 mmHg high pressure, Piezol-mediated calcium influx was stronger than that in 0 mmHg group, hut decreased after Piezol knockdown.Treated with Yodal at 0 mmHg, the expression of contractile phenotvpe-related protein decreased while the expression of synthetic phenotvpe-re- lated protein increased compared with DMSO group..\Jfter using GsMTx4 to inhibit or siRNA to knockdown Piezol at 180 mmHg,the expression of contractile phe- notvpe-related protein increased and the expression of synthetic phenotype-related protein decreased compared with the control group.Conclusion Piezol promotes the transition from contractile phenotvpe to syn-thetic phenotvpe of CASMCs induced by high hydrostatic pressure.