Hypercholesterolemia inhibits re-endothelialization of arterial injuries by TRPC channel activation.
Hypercholesterolemia inhibits re-endothelialization of arterial injuries by TRPC channel activation.
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DOI：
10.1016/j.jvs.2014.04.033
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发表时间：
2015-10
影响因子：
4.3
通讯作者：
Graham LM
中科院分区：
文献类型：
--
作者：
Rosenbaum MA;Chaudhuri P;Graham LM
动脉损伤后，内皮细胞（EC）迁移是必不可少的愈合，但脂质氧化产物激活TRPC 6和TRPC 5离子通道，导致细胞内钙离子增加和抑制EC迁移在体外。本研究的目的是进一步评估TRPC通道在体外EC迁移中的作用，并在体内模型中验证体外结果。培养小鼠主动脉内皮细胞，并在剃刀刮擦试验中评估溶血磷脂酰胆碱（lysoPC）（氧化LDL中的主要溶血磷脂）对迁移的影响。在接受食物或高胆固醇（HC）饮食的野生型（WT）、TRPC 6-/-和TRPC 5-/-小鼠中评价了用电烙术造成颈动脉损伤后的EC愈合。LysoPC抑制WT EC的EC迁移至基线的22%，TRPC 5-/- EC迁移至基线的53%，但对TRPC 6-/- EC迁移的影响极小。高胆固醇血症严重损害了体内EC愈合，在喂食普通饲料和喂食HC的WT小鼠中，分别有51.4±1.8%和24.9±2.0%的损伤在第5天与EC重新接触（P<0.001）。高胆固醇血症不损害TRPC 6-/-小鼠的愈合，在普通饲料喂养和HC喂养的TRPC 6-/-小鼠中的覆盖率分别为48.4±3.4%和46.8±1.6%。高胆固醇血症在TRPC 5-/-小鼠中具有降低的抑制作用，在喂食普通饲料和喂食HC的TRPC 5-/-小鼠中EC覆盖率分别为51.7±3.0%和37.7±1.4%。结果表明，TRPC 6和TRPC 5通道的激活是高胆固醇血症小鼠动脉损伤的内皮愈合受损的关键因素。
After arterial injury, endothelial cell (EC) migration is essential for healing, but lipid oxidation products activate TRPC6 and TRPC5 ion channels leading to increased intracellular calcium and inhibition of EC migration in vitro. The objective of this study was to further evaluate the role of TRPC channels in EC migration in vitro and validate in vitro findings in an in vivo model. Mouse aortic ECs were cultured and the effect of lysophosphatidylcholine (lysoPC), the major lysophospholipid in oxidized LDL, on migration was assessed in a razor scrape assay. EC healing after a carotid injury with electrocautery was evaluated in wild-type (WT), TRPC6-/-, and TRPC5-/- mice receiving either a chow or high cholesterol (HC) diet. LysoPC inhibited EC migration of WT ECs to 22% of baseline, TRPC5-/- EC migration to 53% of baseline but had minimal effect on TRPC6-/- EC migration. Hypercholesterolemia severely impaired EC healing in vivo, with 51.4±1.8% and 24.9±2.0% of the injury resurfaced with ECs at 5 days in chow-fed and HC-fed WT mice, respectively (P<.001). Hypercholesterolemia did not impair healing in TRPC6-/- mice, with coverage of 48.4±3.4% and 46.8±1.6% in chow-fed and HC-fed TRPC6-/- mice, respectively. Hypercholesterolemia had a reduced inhibitory effect in TRPC5-/- mice, with EC coverage of 51.7±3.0% and 37.7±1.4% in chow-fed and HC-fed TRPC5-/- mice, respectively. Results suggest that activation of TRPC6 and TRPC5 channels are key contributors to impaired endothelial healing of arterial injuries in hypercholesterolemic mice.
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影响因子：
5.3
作者：
Dietrich, A;Schnitzler, MMY;Birnbaumer, L
通讯作者：
Birnbaumer, L
影响因子：
3.3
作者：
Chaudhuri, Pinaki;Colles, Scott M.;Graham, Linda M.
通讯作者：
Graham, Linda M.
影响因子：
15.9
作者：
Murugesan, G;Fox, PL
通讯作者：
Fox, PL
TRPC5通道对抗氧化剂和羟基苯甲酸的敏感性。
DOI：
10.1074/jbc.m110.196956
发表时间：
2011-02-18
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Naylor J;Al-Shawaf E;McKeown L;Manna PT;Porter KE;O'Regan D;Muraki K;Beech DJ
通讯作者：
Beech DJ
影响因子：
1.7
作者：
Dasari, Sameera;Abramowitz, Joel;Gulledge, Allan T.
通讯作者：
Gulledge, Allan T.