Creating a mouse model resistant to induced ischemic stroke and cardiovascular damage.
Creating a mouse model resistant to induced ischemic stroke and cardiovascular damage.
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创建对诱发缺血性中风和心血管损伤的耐小鼠模型。
DOI：
10.1038/s41598-018-19661-y
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发表时间：
2018-01-26
影响因子：
4.6
通讯作者：
Ruan KH
中科院分区：
文献类型：
--
作者：
Ling QL;Mohite AJ;Murdoch E;Akasaka H;Li QY;So SP;Ruan KH
血管前列腺素由环加氧酶 (COX) 产生的中间体前列腺素 (PG) H2 异构化而成，对血管系统发挥多种作用，包括保护性和破坏性。在内皮功能障碍期间，血管保护剂前列环素/前列腺素 I2 (PGI2) 减少，而炎症性 PGE2 和血栓性 TXA2 增加。因此，我们的研究目的是通过 COX-1 和前列环素合酶 (PGIS) 的酶促工程生成体内模型来控制 PGH2 代谢，从而逆转这一事件。 COX-1 和 PGIS 基因与 10 个残基氨基酸接头连接，形成单链酶复合物 (SCHEC)，即 COX-1-10aa-PGIS。使用原核显微注射方法产生 FVB/N 背景的转基因 (CP-Tg) 小鼠。我们首先证实了各种 CP-Tg 小鼠组织中 COX-1-10aa-PGIS 的 mRNA 和蛋白表达，以及循环 PGI2 的上调。然后我们检查了这些小鼠的心血管功能。我们的 CP-Tg 小鼠通过诱导颈动脉阻塞、急性血栓性中风和动脉停滞、血管紧张素诱导的外周血管收缩以及接受高脂肪饮食后的肝脂质积累，表现出对血管攻击的显着抵抗力。与野生型小鼠相比，它们的寿命也更长。这项研究提出了利用酶工程调节细胞花生四烯酸衍生的 PGH2 代谢物来对抗心血管疾病的可能性。
Vascular prostanoids, isomerized from an intermediate prostaglandin (PG), H2, produced by cyclooxygenase (COX), exert various effects on the vascular system, both protective and destructive. During endothelial dysfunction, vascular protector prostacyclin/prostaglandin I2 (PGI2) is decreased, while inflammatory PGE2 and thrombotic TXA2 are increased. Therefore, our research aim was to reverse the event by controlling PGH2 metabolism by generating an in vivo model via enzymatic engineering of COX-1 and prostacyclin synthase (PGIS). The COX-1 and PGIS genes were linked to a 10-residue amino acid linker to form a Single-chain Enzyme Complex (SCHEC), COX-1-10aa-PGIS. Transgenic (CP-Tg) mice in a FVB/N background were generated using the pronuclear microinjection method. We first confirmed mRNA and protein expression of COX-1-10aa-PGIS in various CP-Tg mouse tissues, as well as upregulation of circulating PGI2. We then examined the cardiovascular function of these mice. Our CP-Tg mice exhibited marked resistance to vascular assault through induced carotid arterial blockage, acute thrombotic stroke and arterial arrest, angiotensin-induced peripheral vasoconstriction, and hepatic lipid accumulation after receiving a high-fat diet. They also had a longer lifespan compared with wild-type mice. This study raises the possibility of fighting cardiovascular diseases by regulating cellular arachidonic acid-derived PGH2 metabolites using enzymatic engineering.
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影响因子：
7.4
作者：
Huang D;Ren L;Qiu CS;Liu P;Peterson J;Yanagawa Y;Cao YQ
通讯作者：
Cao YQ
DOI：
10.1016/j.healun.2013.01.1055
发表时间：
2013-05
期刊：
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
影响因子：
--
作者：
Siehr SL;Ivy DD;Miller-Reed K;Ogawa M;Rosenthal DN;Feinstein JA
通讯作者：
Feinstein JA
影响因子：
7.3
作者：
Avendano, M. S.;Martinez-Revelles, S.;Briones, A. M.
通讯作者：
Briones, A. M.
影响因子：
46.9
作者：
Castellana M;Wilson MZ;Xu Y;Joshi P;Cristea IM;Rabinowitz JD;Gitai Z;Wingreen NS
通讯作者：
Wingreen NS
影响因子：
4.6
作者：
Sasaki Y;Kamiyama S;Kamiyama A;Matsumoto K;Akatsu M;Nakatani Y;Kuwata H;Ishikawa Y;Ishii T;Yokoyama C;Hara S
通讯作者：
Hara S