Fluid shear stress regulates placental growth factor expression via heme oxygenase 1 and iron.
Fluid shear stress regulates placental growth factor expression via heme oxygenase 1 and iron.
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DOI：
10.1038/s41598-021-94559-w
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发表时间：
2021-07-21
影响因子：
4.6
通讯作者：
Lovern PC
中科院分区：
文献类型：
--
作者：
Rashdan NA;Zhai B;Lovern PC
增加的流体切应力(FSS)是动脉生成的关键启动刺激，动脉生成是侧枝小动脉因上游闭塞而向外重塑的反应。胎盘生长因子(PLGF)是一种重要的动脉形成介质。我们以前发现，在体外和体外，FSS的升高都以一种依赖于活性氧物种(ROS)的方式增加PLGF。血红素加氧酶-1(HO-1)是一种细胞保护酶，可在应激状态下上调表达，具有促动脉生成作用。在本研究中，我们使用分离的小鼠肠系膜小动脉以及人冠状动脉内皮细胞(EC)和血管内皮细胞(SMC)的共同培养来验证HO-1介导FSS对PLGF影响的假设。HO-1mRNA在共培养和血管中均随着流量和剪切力的增加而增加。锌原卟啉抑制HO-1和HO-1基因敲除均可阻断FSS对PLGF的作用。相反，HO-1活性的诱导增加了PLGF。为了确定哪种HO-1产物上调PLGF，用CO供体(CORM-A1)、胆绿素、柠檬酸铁铵(FAC)或铁-氮三乙酸铁(Fe-NTA)处理共培养细胞。其中FAC和Iron-NTA诱导PLGF表达增加。这项研究表明，FSS通过铁诱导促动脉生成PLGF，提示补铁是一种新的潜在的血管重建治疗方法。
Increased fluid shear stress (FSS) is a key initiating stimulus for arteriogenesis, the outward remodeling of collateral arterioles in response to upstream occlusion. Placental growth factor (PLGF) is an important arteriogenic mediator. We previously showed that elevated FSS increases PLGF in a reactive oxygen species (ROS)-dependent fashion both in vitro and ex vivo. Heme oxygenase 1 (HO-1) is a cytoprotective enzyme that is upregulated by stress and has arteriogenic effects. In the current study, we used isolated murine mesentery arterioles and co-cultures of human coronary artery endothelial cells (EC) and smooth muscle cells (SMC) to test the hypothesis that HO-1 mediates the effects of FSS on PLGF. HO-1 mRNA was increased by conditions of increased flow and shear stress in both co-cultures and vessels. Both inhibition of HO-1 with zinc protoporphyrin and HO-1 knockdown abolished the effect of FSS on PLGF. Conversely, induction of HO-1 activity increased PLGF. To determine which HO-1 product upregulates PLGF, co-cultures were treated with a CO donor (CORM-A1), biliverdin, ferric ammonium citrate (FAC), or iron-nitrilotriacetic acid (iron-NTA). Of these FAC and iron-NTA induced an increase PLGF expression. This study demonstrates that FSS acts through iron to induce pro-arteriogenic PLGF, suggesting iron supplementation as a novel potential treatment for revascularization.
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影响因子：
10.8
作者：
Jazwa A;Stepniewski J;Zamykal M;Jagodzinska J;Meloni M;Emanueli C;Jozkowicz A;Dulak J
通讯作者：
Dulak J
影响因子：
3.7
作者：
Iwasaki H;Kawamoto A;Tjwa M;Horii M;Hayashi S;Oyamada A;Matsumoto T;Suehiro S;Carmeliet P;Asahara T
通讯作者：
Asahara T
影响因子：
5.6
作者：
Jansen T;Daiber A
通讯作者：
Daiber A
DOI：
10.1016/s1385-299x(96)00027-x
发表时间：
1997-05-01
期刊：
BRAIN RESEARCH PROTOCOLS
影响因子：
--
作者：
Ewing, JF;Maines, MD
通讯作者：
Maines, MD
DOI：
10.1111/j.1582-4934.2008.00494.x
发表时间：
2009-09-01
影响因子：
5.3
作者：
Kartikasari, Apriliana E. R.;Wagener, Frank A. D. T. G.;Winkels, Dorine W.
通讯作者：
Winkels, Dorine W.