Mesenchymal stem cells suppress cardiac alternans by activation of PI3K mediated nitroso-redox pathway.
Mesenchymal stem cells suppress cardiac alternans by activation of PI3K mediated nitroso-redox pathway.
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间充质干细胞通过激活PI3K介导的硝基 - 雷克斯途径来抑制心脏替代品。
DOI：
10.1016/j.yjmcc.2016.05.014
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发表时间：
2016-09
影响因子：
5
通讯作者：
Laurita, Kenneth R.
中科院分区：
文献类型：
--
作者：
Sattayaprasert, Prasongchai;Nassal, Drew M.;Wan, Xiaoping;Deschenes, Isabelle;Laurita, Kenneth R.
The paracrine action of non-cardiac progenitor cells is robust, but not well understood. Mesenchymal stem cells (MSC) have been shown to enhance calcium (Ca++) cycling in myocytes. Therefore, we hypothesized that MSCs can suppress cardiac alternans, an important arrhythmia substrate, by paracrine action on Ca++ cycling. Human cardiac myocyte monolayers derived from iPS cells (hCM) were cultured without or with human MSCs (hMSC) directly or plated on a transwell insert. Ca++ transient alternans (Ca++ ALT) and Ca++ transient duration (CaD) were measured from hCM monolayers following application of 200 μM H2O2. Ca++ ALT in hCM was significantly decreased when cultured with hMSCs directly (97%, p<0.0001) and when cultured with hMSC in the transwell insert (80%, P<0.0001). When hCM with hMSCs were pretreated with PI3K or eNOS inhibitors, Ca++ ALT was larger than baseline by 20% (p<0.0001) and 36% (p<0.0001), respectively. In contrast, Ca++ ALT was reduced by 89% compared to baseline (p<0.0001) when hCM monolayers without hMSCs were pretreated with 20 μM GSNO. In all experiments, changes in Ca++ ALT were mirrored by changes in CaD. Finally, real time quantitative PCR revealed no significant differences in mRNA expression of RyR2, SERCA2a, and phospholamban between hCM cultured with or without hMSCs. Ca++ ALT is suppressed by hMSCs in a paracrine fashion due to activation of a PI3K-mediated nitroso-redox pathway. These findings demonstrate, for the first time, how stem cell therapy might be antiarrhythmic by suppressing cardiac alternans through paracrine action on Ca++ cycling.
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影响因子：
120.7
作者：
Heldman, Alan W.;DiFede, Darcy L.;Fishman, Joel E.;Zambrano, Juan P.;Trachtenberg, Barry H.;Karantalis, Vasileios;Mushtaq, Muzammil;Williams, Adam R.;Suncion, Viky Y.;McNiece, Ian K.;Ghersin, Eduard;Soto, Victor;Lopera, Gustavo;Miki, Roberto;Willens, Howard;Hendel, Robert;Mitrani, Raul;Pattany, Pradip;Feigenbaum, Gary;Oskouei, Behzad;Byrnes, John;Lowery, Maureen H.;Sierra, Julio;Pujol, Mariesty V.;Delgado, Cindy;Gonzalez, Phillip J.;Rodriguez, Jose E.;Bagno, Luiza Lima;Rouy, Didier;Altman, Peter;Foo, Cheryl Wong Po;da Silva, Jose;Anderson, Erica;Schwarz, Richard;Mendizabal, Adam;Hare, Joshua M.
通讯作者：
Hare, Joshua M.
影响因子：
24
作者：
Hare, Joshua M.;Traverse, Jay H.;Henry, Timothy D.;Dib, Nabil;Strumpf, Robert K.;Schulman, Steven P.;Gerstenblith, Gary;DeMaria, Anthony N.;Denktas, Ali E.;Gammon, Roger S.;Hermiller, James B., Jr.;Reisman, Mark A.;Schaer, Gary L.;Sherman, Warren
通讯作者：
Sherman, Warren
影响因子：
20.1
作者：
Irie T;Sips PY;Kai S;Kida K;Ikeda K;Hirai S;Moazzami K;Jiramongkolchai P;Bloch DB;Doulias PT;Armoundas AA;Kaneki M;Ischiropoulos H;Kranias E;Bloch KD;Stamler JS;Ichinose F
通讯作者：
Ichinose F
影响因子：
20.1
作者：
Karantalis V;DiFede DL;Gerstenblith G;Pham S;Symes J;Zambrano JP;Fishman J;Pattany P;McNiece I;Conte J;Schulman S;Wu K;Shah A;Breton E;Davis-Sproul J;Schwarz R;Feigenbaum G;Mushtaq M;Suncion VY;Lardo AC;Borrello I;Mendizabal A;Karas TZ;Byrnes J;Lowery M;Heldman AW;Hare JM
通讯作者：
Hare JM
影响因子：
37.8
作者：
Chang, MG;Tung, L;Abraham, R
通讯作者：
Abraham, R