Cardiac uptake of minocycline and mechanisms for in vivo cardioprotection.
Cardiac uptake of minocycline and mechanisms for in vivo cardioprotection.
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DOI：
10.1016/j.jacc.2008.06.028
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发表时间：
2008-09-23
影响因子：
24
通讯作者：
Villarreal, Francisco
中科院分区：
文献类型：
--
作者：
Romero-Perez, Diego;Fricovsky, Eduardo;Yamasaki, Katrina Go;Griffin, Michael;Barraza-Hidalgo, Maraliz;Cillmann, Wolfgang;Villarreal, Francisco
米诺环素转运到心肌细胞，在正常和缺血心肌中浓缩，并作为体内心脏保护剂的能力进行了检查。我们还确定了米诺环素作为心肌氧化应激和基质金属蛋白酶（MMP）活性降低剂的能力。具有减少心肌缺血性损伤潜力的化合物的鉴定具有极大的兴趣。四环素类（TTC）是具有多效性细胞保护特性的抗生素，可在正常和病变组织中蓄积。米诺环素是高度亲脂性的，并已显示出作为一种可能的心脏保护剂的前景。然而，米诺环素作为体内心脏保护剂的潜力以及实现该作用的方法还不清楚。大鼠进行45分钟的缺血和48小时的再灌注。在开胸术前48小时和开胸术后48小时，用溶剂或50 mg/kg/天米诺环素处理动物。组织样品用于生化测定，培养的心肌细胞用于米诺环素摄取实验。米诺环素显著降低梗死面积（1033%），组织MMP-9活性和氧化应激。与血液相比，米诺环素在正常（0.5 mM）和缺血区域（1.1 mM）中的浓度分别为2.24倍和2.50倍。新生大鼠心脏成纤维细胞，肌细胞和成人成纤维细胞表现出时间和温度依赖性摄取米诺环素的水平，接近正常心肌。鉴于观察到的高细胞内水平和体外抗氧化剂和MMP抑制剂能力评估的结果，米诺环素可能通过质量作用效应限制心肌缺血性损伤。
The ability of minocycline to be transported into cardiac cells, concentrate in normal and ischemic myocardium and act as in vivo cardioprotector was examined. We also determined minocycline's capacity to act as a reducer of myocardial oxidative stress and matrix metalloproteinase (MMP) activity. The identification of compounds with the potential to reduce myocardial ischemic injury is of great interest. Tetracyclines (TTCs) are antibiotics with pleiotropic cytoprotective properties that accumulate in normal and diseased tissues. Minocycline is highly lipophilic and has shown promise as a possible cardioprotector. However, minocycline's potential as an in vivo cardioprotector as well as the means by which this action is attained are not well understood. Rats were subjected to 45 min of ischemia and 48 h of reperfusion. Animals were treated 48 h before and 48 h after thoracotomy with either vehicle or 50 mg/kg/day minocycline. Tissue samples were used for biochemical assays and cultured cardiac cells for minocycline uptake experiments. Minocycline significantly reduced infarct size (∼33%), tissue MMP-9 activity and oxidative stress. Minocycline was concentrated ∼24-fold in normal (0.5 mM) and ∼50-fold in ischemic regions (1.1 mM) vs. blood. Neonatal rat cardiac fibroblasts, myocytes and adult fibroblasts demonstrate a time- and temperature-dependent uptake of minocycline to levels that approximate those of normal myocardium. Given the high intracellular levels observed and results from the assessment of in vitro antioxidant and MMP inhibitor capacities, it is likely that minocycline acts to limit myocardial ischemic injury via mass action effects.
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影响因子：
3.6
作者：
García, RA;Pantazatos, DP;Villarreal, FJ
通讯作者：
Villarreal, FJ
影响因子：
7.3
作者：
Leon, H.;Baczko, I.;Schulz, R.
通讯作者：
Schulz, R.
影响因子：
5
作者：
Bastos, Leandro Francisco S.;Merlo, Leonardo A.;Coelho, Marcio M.
通讯作者：
Coelho, Marcio M.
影响因子：
2.9
作者：
Senft, AP;Dalton, TP;Shertzer, HG
通讯作者：
Shertzer, HG
影响因子：
4.3
作者：
BAKER, PJ;EVANS, RT;GENCO, RJ
通讯作者：
GENCO, RJ