Abstract
We previously reported that eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid (n-3 PUFA), effectively inhibits sphingosylphosphorylcholine (SPC)-induced Ca2+-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 Ca2+-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.
Highlights
The two families of PUFAs, omega-3 (n-3) and omega-6 (n-6) PUFAs, are classified based on the location of the last double bond relative to the terminal methyl group of the molecule[11,12]
We have demonstrated that n-3 PUFAs, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), inhibited SPC-induced Ca2+-sensitization of vascular smooth muscle (VSM) contraction[27], it is unknown whether docosapentaenoic acid (DPA), an intermediate product between EPA and DHA, is capable of inhibiting SPC-induced VSM contraction
SPC stimulation caused a minor contraction in tissue strips pretreated with 60 μM n-3 and n-6 DPA compared with strong contraction in vehicle control (Fig. 2a–c), showing that pretreatment with n-3 and n-6 DPA significantly inhibited SPC-induced contraction by 73.00 ± 2.31% and 95.00 ± 2.89%, respectively (Fig. 2f)
Summary
The two families of PUFAs, omega-3 (n-3) and omega-6 (n-6) PUFAs, are classified based on the location of the last double bond relative to the terminal methyl group of the molecule[11,12]. Accumulating evidence demonstrates that n-3 PUFAs, including EPA and docosahexaenoic acid (DHA) from fish and fish oils, are beneficial in prevention of cardiovascular diseases[13,14,15,16,17]. Some studies indicate that n-6 PUFAs have anti-inflammatory properties[21,22,23,24], and higher consumption of n-6 PUFAs appears safe and may reduce the risk of cardiovascular disease[25,26]. Rissanen et al reported that a high proportion of fish-derived DHA and DPA in serum is associated with a decreased risk of acute coronary syndrome[31]. Some studies have evaluated the link between n-3 DPA and the risk for cardiovascular disease, there is no direct evidence on whether n-3 and n-6 DPA affect Ca2+-sensitization of VSM contraction. The purpose of the present study was to (i) investigate and compare the effects of individual n-3 DPA and n-6 DPA on SPC-induced Ca2+-sensitization and Ca2+-dependent contraction of VSM; (ii) determine the effects of n-3 and n-6 DPA on intracellular [Ca2+] by simultaneously measuring [Ca2+]i and VSM contraction; and (iii) examine the mechanism of how n-3 and n-6 DPA affect SPC-induced Ca2+-sensitization of VSM contraction
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