Inflammatory reaction versus endogenous peroxisome proliferator-activated receptors expression, re-exploring secondary organ complications of spontaneously hypertensive rats.
BACKGROUND
The chronic pathological changes in vascular walls of hypertension may exert destructive effects on multiple organ systems. Accumulating evidence indicates that inflammatory reactions are involved in the pathological changes of hypertension. Three peroxisome proliferator-activated receptors (PPARs) have been identified: PPARalpha, PPARbeta/delta, and PPARgamma, all of which have multiple biological effects, especially the inhibition of inflammation. The aim of this study was to evaluate PPAR isoforms expression profile in important organs of spontaneously hypertensive rats (SHR) and to understand the modulation of endogenous PPAR isoforms under inflammatory condition.


METHODS
Tissues (kidney, liver, heart, and brain) were dissected from SHR and age-matched control Wistar-Kyoto rats (WKY) to investigate the abundance of PPAR isoforms and PPAR-responsive genes (acyl-CoA oxidase and CD36). The expression of CCAAT/enhancer-binding protein delta (C/EBPdelta), which can trans-activate PPARgamma expression, was also observed. The inflammatory response was analyzed by the expression of inflammatory mediators inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, interleukin-1 beta (IL-1beta), and tumor necrosis factor alpha (TNFalpha), and formation of carbonyl and nitrated proteins.


RESULTS
The expressions of 3 PPAR isoforms and PPAR-responsive genes were markedly upregulated in SHR compared with those of WKY. Specifically, the expression of PPARalpha protein in the kidney, liver, heart and brain increased by 130.76%, 91.48%, 306.24%, and 90.70%; PPARbeta/delta upregulated by 109.34%, 161.98%, 137.04%, and 131.66%; PPARgamma increased by 393.76%, 193.17%, 559.29%, and 591.18%. In consistent with the changes in PPARgamma, the expression of C/EBPdelta was also dramatically elevated in SHR. Inflammatory mediators expressions were significantly increased in the most organs of SHR than WKY. As a consequence, increased formation of carbonyl and nitrated proteins were also observed in the most organs of SHR.


CONCLUSIONS
These findings suggest an enhanced inflammatory response in the organs of SHR, which might play a key role in pathogenesis of hypertension and secondary organ complications. Changes (increases) in PPARs expression may reflect a compensatory mechanism to the inflammatory status of hypertensive rats.
Sun
Li
L
Murad Research Institute for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Ke
Yan
Y
Zhu
Chun-yun
CY
Tang
Ning
N
Tian
Deng-ke
DK
Gao
Yue-hong
YH
Zheng
Jian-pu
JP
Bian
Ka
K
D000818:Animals; D001794:Blood Pressure; D015153:Blotting, Western; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006973:Hypertension / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007249:Inflammation / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism*; D010991:Plethysmography / Q000379:methods; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
D019040:E-Selectin; D053583:Interleukin-1beta; D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1