Department of Molecular and Cellular Physiology, Yamaguchi University, Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
Sci Rep. 2017 Feb 7;7:36368. doi: 10.1038/srep36368.
We previously reported that eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid (n-3 PUFA), effectively inhibits sphingosylphosphorylcholine (SPC)-induced Ca-sensitization of vascular smooth muscle (VSM) contraction which is a major cause of cardiovascular and cerebrovascular vasospasm, and EPA is utilized clinically to prevent cerebrovascular vasospasm. In this study, we clearly demonstrate that docosapentaenoic acid (DPA), which exists in two forms as omega-3 (n-3) and omega-6 (n-6) PUFA, strongly inhibits SPC-induced contraction in VSM tissue and human coronary artery smooth muscle cells (CASMCs), with little effect on Ca-dependent contraction. Furthermore, n-3 and n-6 DPA inhibited the activation and translocation of Rho-kinase from cytosol to cell membrane. Additionally, SPC-induced phosphorylation of myosin light chain (MLC) was inhibited in n-3 and n-6 DPA pretreated smooth muscleVSM cells and tissues. In summary, we provide direct evidence that n-3 and n-6 DPA effectively equally inhibits SPC-induced contraction by inhibiting Rho-kinase activation and translocation to the cell membrane.
我们之前曾报道，二十碳五烯酸（EPA）是一种ω-3 多不饱和脂肪酸（n-3PUFA），可有效抑制神经鞘氨醇磷酸胆碱（SPC）诱导的血管平滑肌（VSM）收缩的钙敏化，这是心血管和脑血管痉挛的主要原因，EPA 临床上用于预防脑血管痉挛。在这项研究中，我们明确证明了二十二碳五烯酸（DPA），它以两种形式存在，即 ω-3（n-3）和 ω-6（n-6）PUFA，强烈抑制 VSM 组织和人冠状动脉平滑肌细胞（CASMC）中的 SPC 诱导的收缩，对 Ca 依赖性收缩几乎没有影响。此外，n-3 和 n-6 DPA 抑制 Rho-激酶从细胞质向细胞膜的激活和易位。此外，SPC 诱导的肌球蛋白轻链（MLC）磷酸化在 n-3 和 n-6 DPA 预处理的平滑肌 VSM 细胞和组织中受到抑制。总之，我们提供了直接证据表明，n-3 和 n-6 DPA 通过抑制 Rho-激酶的激活和向细胞膜的易位，有效地同等抑制 SPC 诱导的收缩。
