Hu Jun, Shen Tingting, Xie Jun, Wang Siyang, He Yue, Zhu Fu
Xuhui Central Hospital, Shanghai Clinical Research Center, China Academy of Sciences, Shanghai 200031, P.R. China.
Exp Ther Med. 2017 Dec;14(6):5896-5902. doi: 10.3892/etm.2017.5318. Epub 2017 Oct 17.
Hypertension is a leading risk factor for morbidity and mortality. Previous studies have reported that curcumin has anti-oxidation and anti-aging effects and inhibits histone deacetylase activity. However, it is still unclear whether curcumin could protect against vascular injury induced by hypertension. Thus, the current study examined the therapeutic effects and mechanism of curcumin on vascular injury induced by hypertension in spontaneous hypertensive rats (SHRs). The present study revealed that curcumin may improve vascular structure and attenuate coronary artery pathology. Moderate doses (~50 mg) of curcumin were most effective in treating coronary artery injury in SHRs. Moreover, the results of immunohistochemical analysis indicated that the expression levels of histone deacetylase 1 (HDAC1), matrix metalloproteinase-2 (MMP-2) and transforming growth factor β (TGFβ) decreased in the curcumin treatment group, compared with the non-treated group or the negative control group. However, the expression of tissue inhibitor of metalloproteinase 1 (TIMP1) did not visibly decrease. Furthermore, chromatin immunoprecipitation results suggested that curcumin was capable of promoting the transcription activation of TIMP1 through suppressing HDAC1 expression and increasing histone H3 acetylation at the TIMP1 promoter region in SHRs. In conclusion, curcumin could relieve extracellular matrix degradation and interstitial fibrosis induced by hypertension, and lower blood pressure. It could also serve a function in improving vascular structure through inhibiting the expression of HDAC1, thereby promoting TIMP1 transcription activation and suppressing the expression of MMP-2 and TGFβ.
高血压是发病和死亡的主要危险因素。先前的研究报道，姜黄素具有抗氧化和抗衰老作用，并能抑制组蛋白脱乙酰酶活性。然而，姜黄素是否能预防高血压引起的血管损伤仍不清楚。因此，本研究检测了姜黄素对自发性高血压大鼠（SHRs）高血压诱导的血管损伤的治疗作用及机制。本研究表明，姜黄素可能改善血管结构并减轻冠状动脉病理变化。中等剂量（约50mg）的姜黄素对治疗SHRs的冠状动脉损伤最有效。此外，免疫组化分析结果表明，与未治疗组或阴性对照组相比，姜黄素治疗组中组蛋白脱乙酰酶1（HDAC1）、基质金属蛋白酶-2（MMP-2）和转化生长因子β（TGFβ）的表达水平降低。然而，金属蛋白酶组织抑制剂1（TIMP1）的表达没有明显降低。此外，染色质免疫沉淀结果表明，姜黄素能够通过抑制HDAC1表达并增加SHRs中TIMP1启动子区域的组蛋白H3乙酰化来促进TIMP1的转录激活。总之，姜黄素可以减轻高血压诱导的细胞外基质降解和间质纤维化，并降低血压。它还可以通过抑制HDAC1的表达来改善血管结构，从而促进TIMP1转录激活并抑制MMP-2和TGFβ的表达。
