Effects Of Adipose Tissue-Derived Mesenchymal Stem Cells In Pulmonary Arterial Calcium Channels On Pulmonary Artery Hypertension By Monocrotaline In Rats

Objective: To investigate effects of adipose tissue-derived mesenchymalstem cells（ADMSC） on pulmonary aterial calcium regulating channels in pulmonaryartery hypertension(PAH) induced by monocrotaline(MCT) in rats.Methods: ADMSC were obtained from subcutaneous adipose of rat，s groinand was isolated by collagenase type I.Twenty-four Sprague-Dawley rats wererandomly assigned into three groups： normal control (Ctr), pulmonary arterialhypertension (PAH), ADMSC treated groups. A dose of40mg/Kg monocrotalineintraperitoneally was given in PAH and ADMSC treated group，and untreated ratswere given1ml normal saline intraperitoneally as control. ADMSC (1X106/ml) weredelivered to rats by injection into left jugular vein2wk after administration ofmonocrotaline and1ml normal saline was given in PAH,and control untreatedgroup.4weeks after ADMSC, mean of pulmonary arterial pressure（MPAP） weremeasured by catheterization and right ventricular hypertrophy index weremeasured[RVHI＝RV/(LV+S)], The pulmonary arterial trunks from each group werecollected. The mRNA and protein expression for Cavα1c, SERCA-2a, IP3R-1,TRPC1， TRPC6in pulmonary artery was determined by RT-PCR andWestern-Blotting.Result:1) MPAP and RVHI were significantly higher in PAH, as compared with Ctrgroup. MPAP and RVHI were significantly decreased after treatment of ADMSC[MPAP:mmHg Ctr(15.03±0.87) VS PAH(32.22±0.71),ADMCS(21.87±0.78)；RVHI：Ctr(25.67±1.26) VS PAH(53.44±2.13)，ADMSC(38.97±1.59)%，P <0.05respectively]. 2) In comparison with PAH, the calcium regulating channel mRNA expression ofCavα1c、TRC1and TRPC6were obviously decreased after treatment of ADMSC.(P<0.05respectively).[Cavα1c: Ctr(0.185±0.036) VS PAH(0.543±0.059)，ADMSC(0.336±0.072)； TRPC1： Ctr(0.225±0.055) VS PAH(0.613±0.069)，ADMSC(0.444±0.056)； TRPC6： Ctr(0.844±0.068) VS PAH(0.892±0.055)，ADMSC(0.271±0.052)，P <0.05respectively] And in comparison with PAH,there werean significant increase in the expression of SERCA-2a and IP3R-1in mRNA levelafter treatment of ADMSC [SERCA-2a: Ctr(0.566±0.066) VS PAH(0.102±0.021)，ADMSC(0.292±0.032)； IP3R-1： Ctr(1.181±0.139) VS PAH(0.100±0.017)，ADMSC(0.340±0.057)，P <0.05respectively].3) In comparison with PAH, the calcium channel protein expression of Cavα1c、TRC1and TRPC6were obviously decreased after treatment of ADMSC.[Cavα1c:Ctr(0.063±0.009) VS PAH(0.204±0.031)，ADMSC(0.095±0.011)；TRPC1：Ctr(0.055±0.006)VS PAH(0.098±0.014)， ADMSC(0.078±0.008)； TRPC6： Ctr(0.095±0.011) VSPAH(0.204±0.031)，ADMSC(0.063±0.009)，P <0.05respectively] And in comparisonwith PAH,there were an significant increase in the protein expression of SERCA-2aand IP3R-1after treatment of ADMSC [SERCA-2a: Ctr(0.101±0.013) VSPAH(0.050±0.009)， ADMSC(0.063±0.007)； IP3R-1： Ctr(0.829±0.044) VSPAH(0.204±0.031)，ADMSC(0.063±0.009),P <0.05respectively].Conclusions(1) Pulmonary arterial pressure was reduced and right ventricular hypertrophy wereattenuated by ADMSC in monocrotaline-induced pulmonary hypertensive rats.(2)The expression of calcium channel mRNA and protein such as Cavα1c, SERCA-2a,IP3R-1, TRPC1and TRPC6were markedly changed in pulmonary artery inmonocrotaline-induced pulmonary hypertensive rats.(3)Pulmonary arterial pressure was reduced by ADMSC transplanted inmonocrotaline-induced pulmonary hypertensive rats may have related with thechanged of calcium channel such as Cavα1c, SERCA-2a, IP3R-1, TRPC1andTRPC6.