Abstract
C-reactive protein (CRP) is a powerful independent risk factor for cardiovascular diseases. Elevated mechanical strain on vessels induces the local expression of proinflammatory cytokines. We hypothesized that mechanical strain on vessels may induce local CRP expression. Human saphenous vein and internal mammary artery (IMA) rings were stretched in vitro with a mechanical strength of 1, 3, or 5 g. Reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay results showed that mechanical stretching significantly induced CRP mRNA and protein expression in the saphenous vein and IMA rings in a strength-dependent manner reaching a maximum at a mechanical strength of 3 g, but CRP expression returned at strengths of >5 g. In vessels, mechanical strain-induced CRP expression was blocked by two stretch-activated ion channel (SAC) blockers: GdCl3 and streptomycin. Mechanical strain also increased activation of nuclear factor κB (NF-κB), which was detected with a nonradioactive NF-κB p50/p65 EZ-TFA transcription factor assay. Mechanical strain-induced NF-κB activation was blocked by SAC blockers and the NF-κB inhibitor (SN50, H-Ala-Ala-Val-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Val-Gln-Arg-Lys-Arg-Gln-Lys-Leu-Met-Pro-OH). SN50 also blocked mechanical strain-induced CRP expression in vessels. In conclusion, mechanical strain induces CRP expression in IMAs and saphenous veins by activating the SAC-induced NF-κB pathway.
Footnotes
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This work was supported by the National Natural Science Foundation of China [Grant 30770897/C03030201].
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.109.150961.
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ABBREVIATIONS: CRP, C-reactive protein; hsCRP, high-sensitivity C-reactive protein; IL-6, interleukin-6; VSMCs, vascular smooth muscle cells; SAC, stretch-activated ion channel; NF-κB, nuclear factor-κB; IMAs, internal mammary arteries; RT-PCR, reverse transcription-polymerase chain reaction; SN50, H-Ala-Ala-Val-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Val-Gln-Arg-Lys-Arg-Gln-Lys-Leu-Met-Pro-OH; SN50M, H-Ala-Ala-Val-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Leu-Leu-Ala-Pro-Val-Gln-Arg-Asn-Gly-Gln-Lys-Leu-Met-Pro-OH.
- Received January 14, 2009.
- Accepted April 24, 2009.
- The American Society for Pharmacology and Experimental Therapeutics
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