Mechanical strain induces expression of C-reactive protein in human blood vessels.
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: GdCl(3) and streptomycin. Mechanical strain also increased activation of nuclear factor kappaB (NF-kappaB), which was detected with a nonradioactive NF-kappaB p50/p65 EZ-TFA transcription factor assay. Mechanical strain-induced NF-kappaB activation was blocked by SAC blockers and the NF-kappaB 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-kappaB pathway.
Huang
Genya
G
Division of Cardiology, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan II Road, Guangzhou, Guangdong, People's Republic of China.
Luo
Chufan
C
Gu
Xingyuan
X
Wu
Zhongkai
Z
Wang
Zhiping
Z
Du
Zhiming
Z
Hu
Chengheng
C
Tang
Lilong
L
D000368:Aged; D001696:Biomechanical Phenomena / Q000502:physiology; D002097:C-Reactive Protein / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D008323:Mammary Arteries / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D012501:Saphenous Vein / Q000378:metabolism / Q000502:physiology*; D033081:Shear Strength / Q000502:physiology; D013314:Stress, Mechanical
D002097:C-Reactive Protein