Mitochondrial targeted peptides attenuate residual myocardial damage after reversal of experimental renovascular hypertension.
Mitochondrial targeted peptides attenuate residual myocardial damage after reversal of experimental renovascular hypertension.
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DOI：
10.1097/hjh.0b013e3283658a53
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发表时间：
2014-01
影响因子：
4.9
通讯作者：
Lerman LO
中科院分区：
文献类型：
--
作者：
Eirin A;Williams BJ;Ebrahimi B;Zhang X;Crane JA;Lerman A;Textor SC;Lerman LO
肾血管性高血压（RVHT）会增加心血管疾病的发病率和死亡率。经皮腔内肾血管成形术和支架置入术 (PTRS) 的肾血运重建可能会逆转 RVHT，但可能无法完全消除心脏重塑和损伤，这可能是由于持续的心肌损伤所致。 Bendavia 是一种线粒体靶向肽，可通过改善线粒体功能来减少缺血性心肌病。然而，其减轻 RVHT 逆转后残余心肌损伤的潜力尚未被探索。我们假设使用 Bendavia 作为 PTRS 的辅助治疗将改善猪 RVHT 的心脏功能和氧合，并减少心肌损伤。 RVHT（单侧肾动脉狭窄）或对照 6 周后，猪接受 PTRS（或假手术），并辅助连续输注 Bendavia（0.05 mg/kg，静脉注射，PTRS 前 30 分钟至 PTRS 后 3.5 小时）或载体（每次 n = 7）。四周后，通过多探测器计算机断层扫描评估收缩和舒张功能，通过血氧水平依赖性 MRI 评估心肌氧合，并通过离体评估心肌形态、细胞凋亡、线粒体生物发生和纤维化。 PTRS 恢复了两组的血压，但 E/A 比值仍然下降。 RVHT +PTRS +Bendavia 动物的心肌氧合和线粒体生物合成得到改善，心肌炎症、氧化应激和纤维化正常化，与舒张功能的改善相关。在猪 RVHT 的 PTRS 期间辅助使用 Bendavia 可改善舒张功能和氧合，并逆转心肌组织损伤。这种方法可能会提供一种新的策略来保存 RVHT 中的心脏功能和结构。
Renovascular hypertension (RVHT) increases cardiovascular morbidity and mortality. Renal revascularization with percutaneous transluminal renal angioplasty and stenting (PTRS) may reverse RVHT but may not fully regress cardiac remodeling and damage, possibly due to persistent myocardial insults. Bendavia is a mitochondrial targeted peptide that reduces ischemic cardiomyopathy by improving mitochondrial function. However, its potential for attenuating residual myocardial damage after reversal of RVHT has not been explored. We hypothesized that treatment with Bendavia as an adjunct to PTRS would improve cardiac function and oxygenation, and decrease myocardial injury in swine RVHT. After 6 weeks of RVHT (unilateral renal artery stenosis) or control, pigs underwent PTRS (or sham), with adjunct continuous infusion of Bendavia (0.05 mg/kg intravenously, 30 min before to 3.5 h after PTRS) or vehicle (n =7 each). Four weeks later, systolic and diastolic function were assessed by multidetector computed tomography, myocardial oxygenation by blood oxygen level-dependent MRI, and myocardial morphology, apoptosis, mitochondrial biogenesis, and fibrosis evaluated ex vivo. PTRS restored blood pressure in both groups, yet E/A ratio remained decreased. Myocardial oxygenation and mitochondrial biogenesis improved, and myocardial inflammation, oxidative stress, and fibrosis normalized in association with improvement in diastolic function in RVHT +PTRS +Bendavia animals. Adjunct Bendavia during PTRS in swine RVHT improved diastolic function and oxygenation and reversed myocardial tissue damage. This approach may allow a novel strategy for preservation of cardiac function and structure in RVHT.