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Aim To investigate the mechanism of TET1 in cardiac fibrosis induced by high pressure. Methods Wistar rats and spontaneous hypertension rats(SHR) were selected to detected the expression of TET1, TGF-β, COL-1 and COL-3 in myocardium by Western blot; HE and Masson staining were used to detect myocardial pathological changes. Neonatal rat cardiac fibroblasts (NRCFs) were isolated from the ventricles of neonatal Sprague-Dawley rats and stimulated by 0 mm-Hg, 120 mmHg and 180 mmHg high pressure. Immunofluorescence was used to detect the changes of 5-hmC in the NRCFs. The changes of 5-hmC and 5-mC in TGF-β promoter region were detected by qRT-PCR. The expressions of TET1, TGF-β, COL-1 and COL-3 were detected by Western blot. Results Compared with Wistar rats, SHR showed increased blood pressure, increased fibrous collagen in ventricular tissues, and significantly increased expressions of TET1, TGF-P, COL-1 and COL-3. Compared with the 0 mmHg group, 120 mmHg and 180 mmHg group significantly induced the increase of TET1, 5-hmC, TGF-p, COL-1 and COL-3. TET1 knockdown significantly reduced the increase of 5-hmC, TGF-β, COL-1 and COL-3 under 180 mmHg pressure. Besides, knockdown TET1 significantly reduced the level of 5-hmC and increased the level of 5-mC and 5-hmC in the TGF-β promoter region. Conclusions High pressure induced cardiac fibrosis is associated with the promotion of TGF-β promoter demethylation and the increased of TGF-β expression by TET1.
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Abstract Therapy for large symptomatic keloids is often plagued with complicated reconstruction manner and recurrence. This article reports a rare treatment combination for a chest keloid with internal mammary artery perforator flap reconstruction and radiation therapy. We excised the keloid and covered the defect with an internal mammary artery perforator flap. Immediate electron-beam irradiation therapy was applied on the second postoperative day. There was no sign of recurrence over the follow-up period of 18 months. The combination of internal mammary artery perforator flap and immediate radiation therapy is useful when faced with chest keloids of similar magnitude and intractability.