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Novel mechanism of cardiac protection by valsartan: synergetic roles of TGF-β1 and HIF-1α in Ang II-mediated fibrosis after myocardial infarction.

Sui X, Wei H, Wang D - J. Cell. Mol. Med. (2015)

Bottom Line: By blocking with valsartan, a blocker of Ang II type I (AT1) receptor, we confirmed that the up-regulation of TGF-β/Smad and Hif-1α was through the Ang II-mediated pathway.By administering TGF-β or dimethyloxalylglycine, we determined that both TGF-β/Smad and Hif-1α contributed to Ang II-mediated collagen accumulation and a synergetic effect between them was observed.Heart function, infarcted size, wall thickness as well as myocardial vascularization of ischaemic hearts were also significantly improved by valsartan compared with saline and hydralazine.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiothoracic Surgery, The Civil Aviation General Hospital, Chaoyang District, Beijing, China.

No MeSH data available.


Related in: MedlinePlus

Effects of Ang II, valsartan, TGF-1β and DMOG on TGF-1β/Smad and Hif-1α pathways as well as fibrosis-related proteins. (A) Expression of Smad (downstream effector of TGF-1β) when Ang II, valsartan, TGF-1β or DMOG were added. (B) Expression of Hif-1α when Ang II, valsartan, TGF-1β or DMOG were added. (C) Expression of MMP-2 when Ang II, valsartan, TGF-1β or DMOG were added. (D) Expression of MMP-9 when Ang II, valsartan, TGF-1β or DMOG were added. (E) Collagen accumulation when Ang II, valsartan, TGF-1β or DMOG were added. (F) Regulatory network mapped based on in vitro results (n = 3, ** compared with Ang II; ## compared with Val+Ang; $$ compared with Ang+val+TGF; && compared with Ang+Val+DMOG).
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fig02: Effects of Ang II, valsartan, TGF-1β and DMOG on TGF-1β/Smad and Hif-1α pathways as well as fibrosis-related proteins. (A) Expression of Smad (downstream effector of TGF-1β) when Ang II, valsartan, TGF-1β or DMOG were added. (B) Expression of Hif-1α when Ang II, valsartan, TGF-1β or DMOG were added. (C) Expression of MMP-2 when Ang II, valsartan, TGF-1β or DMOG were added. (D) Expression of MMP-9 when Ang II, valsartan, TGF-1β or DMOG were added. (E) Collagen accumulation when Ang II, valsartan, TGF-1β or DMOG were added. (F) Regulatory network mapped based on in vitro results (n = 3, ** compared with Ang II; ## compared with Val+Ang; $$ compared with Ang+val+TGF; && compared with Ang+Val+DMOG).

Mentions: To confirm whether Ang II-induced collagen accumulation was through TGF-β1/Smad and HIF-1α pathways, TGF-β1 (TGF-β1/Smad pathway) and DMOG (agonist of HIF-1α) were administered together with Ang II and valsartan. As shown in Figure2A, Ang II-upregulated Smad was counteracted by valsartan, when TGF-1β was added; the Smad expression was restored, indicating that Ang II inhibited TGF-1β which further inhibited its downstream pathway. The Ang II-induced Hif-1α expression was also suppressed by valsartan and could be restored by DMOG (Fig.2B). Interestingly, valsartan-suppressed Hif-1α under Ang II could also be partly restored by TGF-1β, indicating Hif-1α may be influenced by the TGF-1β pathway to some extent, but addition of DMOG exerted no effects on TGF-1β/Smad.


Novel mechanism of cardiac protection by valsartan: synergetic roles of TGF-β1 and HIF-1α in Ang II-mediated fibrosis after myocardial infarction.

Sui X, Wei H, Wang D - J. Cell. Mol. Med. (2015)

Effects of Ang II, valsartan, TGF-1β and DMOG on TGF-1β/Smad and Hif-1α pathways as well as fibrosis-related proteins. (A) Expression of Smad (downstream effector of TGF-1β) when Ang II, valsartan, TGF-1β or DMOG were added. (B) Expression of Hif-1α when Ang II, valsartan, TGF-1β or DMOG were added. (C) Expression of MMP-2 when Ang II, valsartan, TGF-1β or DMOG were added. (D) Expression of MMP-9 when Ang II, valsartan, TGF-1β or DMOG were added. (E) Collagen accumulation when Ang II, valsartan, TGF-1β or DMOG were added. (F) Regulatory network mapped based on in vitro results (n = 3, ** compared with Ang II; ## compared with Val+Ang; $$ compared with Ang+val+TGF; && compared with Ang+Val+DMOG).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4549028&req=5

fig02: Effects of Ang II, valsartan, TGF-1β and DMOG on TGF-1β/Smad and Hif-1α pathways as well as fibrosis-related proteins. (A) Expression of Smad (downstream effector of TGF-1β) when Ang II, valsartan, TGF-1β or DMOG were added. (B) Expression of Hif-1α when Ang II, valsartan, TGF-1β or DMOG were added. (C) Expression of MMP-2 when Ang II, valsartan, TGF-1β or DMOG were added. (D) Expression of MMP-9 when Ang II, valsartan, TGF-1β or DMOG were added. (E) Collagen accumulation when Ang II, valsartan, TGF-1β or DMOG were added. (F) Regulatory network mapped based on in vitro results (n = 3, ** compared with Ang II; ## compared with Val+Ang; $$ compared with Ang+val+TGF; && compared with Ang+Val+DMOG).
Mentions: To confirm whether Ang II-induced collagen accumulation was through TGF-β1/Smad and HIF-1α pathways, TGF-β1 (TGF-β1/Smad pathway) and DMOG (agonist of HIF-1α) were administered together with Ang II and valsartan. As shown in Figure2A, Ang II-upregulated Smad was counteracted by valsartan, when TGF-1β was added; the Smad expression was restored, indicating that Ang II inhibited TGF-1β which further inhibited its downstream pathway. The Ang II-induced Hif-1α expression was also suppressed by valsartan and could be restored by DMOG (Fig.2B). Interestingly, valsartan-suppressed Hif-1α under Ang II could also be partly restored by TGF-1β, indicating Hif-1α may be influenced by the TGF-1β pathway to some extent, but addition of DMOG exerted no effects on TGF-1β/Smad.

Bottom Line: By blocking with valsartan, a blocker of Ang II type I (AT1) receptor, we confirmed that the up-regulation of TGF-β/Smad and Hif-1α was through the Ang II-mediated pathway.By administering TGF-β or dimethyloxalylglycine, we determined that both TGF-β/Smad and Hif-1α contributed to Ang II-mediated collagen accumulation and a synergetic effect between them was observed.Heart function, infarcted size, wall thickness as well as myocardial vascularization of ischaemic hearts were also significantly improved by valsartan compared with saline and hydralazine.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiothoracic Surgery, The Civil Aviation General Hospital, Chaoyang District, Beijing, China.

No MeSH data available.


Related in: MedlinePlus