Inflammatory reaction versus endogenous peroxisome proliferator- activated receptors expression, re-exploring secondary organ complications of spontaneously hypertensive rats

• Published in: Chinese medical journal 2008-11, Vol.121 (22), p.2305-2311
• Main Authors: Sun, Li, Ke, Yan, Zhu, Chun-yun, Tang, Ning, Tian, Deng-ke, Gao, Yue-hong, Zheng, Jian-pu, Bian, Ka
• Format: Article
• Language: English
• Subjects: Animals; Blood Pressure; Blotting, Western; E-Selectin - genetics; E-Selectin - metabolism; Gene Expression; Hypertension - genetics; Hypertension - metabolism; Hypertension - physiopathology; Inflammation - genetics; Inflammation - metabolism; Inflammation - physiopathology; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Male; Peroxisome Proliferator-Activated Receptors - genetics; Peroxisome Proliferator-Activated Receptors - metabolism; Plethysmography - methods; PPAR alpha - genetics; PPAR alpha - metabolism; PPAR delta - genetics; PPAR delta - metabolism; PPAR gamma - genetics; PPAR gamma - metabolism; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reverse Transcriptase Polymerase Chain Reaction; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - metabolism; 过氧物酶体; 高血压
• ISSN: 0366-6999; 2542-5641
• DOI: 10.1097/00029330-200811020-00017

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： PPARa, PPARβ/δ, and PPARγ, 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 l]ssues （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 （acyI-CoA oxidase and CD36）. The expression of CCAAT/enhancer-binding protein 6 （C/EBP6）, which can trans-activate PPARγ 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-1β）, and tumor necrosis factor alpha （TNFα）, 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 PPARa protein in the kidney, liver, heart and brain increased by 130.76 %, 91.48%, 306.24%, and 90.70%; PPARβ/δ upregulated by 109.34%, 161.98%, 137.04%, and 131.66%; PPARγ increased by 393.76%, 193.17%, 559.29%, and 591.18%. In consistent with the changes in PPARy, the expression of C/EBPδ 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.