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- W1986425314 abstract "432 Post-renal transplant (post-Tx) hypertension (HTN) is associated with chronic graft loss, manifested by renal tubular atrophy (TA) and interstitial fibrosis. Vasoactive compounds play a role in post-Tx HTN and may interact with matrix and fibrogenic pathways, e.g. angiotensin II (AT) upregulating TGF-β1, to alter graft function. We used the reverse-transcription polymerase chain reaction (RT-PCR) to assess intragraft transcriptional regulation of renin, type 1 AT receptor (AT1R), endothelin (ET) converting enzyme (ECE), ETB receptor (ETBR), inducible nitric oxide synthase (iNOS), TGF-β, and metalloproteinase (MP) mRNAs: matrix MP-1 promoter region (MMP-1PR), MMP-2, MMP-3, membrane-type MMP-1, tissue inhibitor of MMP's-2 (TIMP-2) and TIMP-3 in biopsy (bx) samples from stable hypertensive Rtx pts (DBP>90 mmHg). PCR products were quantitated using high performance liquid chromatography. Results were normalized to β-actin mRNA expression. Serum creatinine (Scr), glomerular filtration rate (GFR) and TA on bx also were assessed. MMP1PR mRNA (n=13) was inversely correlated with TA (Spearman corr coeff:−0.72; P=0.02) and Scr (−0.62; P=0.03). MMP1PR mRNA (n=13) also was inversely correlated with TGF-β (−0.82; P=0.0005) and iNOS mRNA expression (−0.61; P=0.02). MMP1PR mRNA positively correlated with TIMP-2 and TIMP-3 mRNA and the HTN genes, AT1R (0.76; P<0.003) and ECE mRNA (0.65; P=0.01). These HTN transcripts also demonstrated significant correlations with clinical variables. (Table)TableA stepwise multiple regression model demonstrated that renin mRNA expression was significantly associated with TA (P=0.01) and that AT1R mRNA expression was the most significant predictor of GFR (P=0.005) and f/u Scr (4-12 mos.) after bx (P=0.012). These data suggest that the coordinated regulation of HTN and MP genes may be important for maintaining graft function. In this context, intragraft HTN gene expression appears to be a powerful predictor of renal function and renal outcomes in post-Tx HTN." @default.
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- W1986425314 date "1999-04-01" @default.
- W1986425314 modified "2023-09-23" @default.
- W1986425314 title "INTRAGRAFT HYPERTENSION AND METALLOPROTEINASE GENE EXPRESSION: MODULATORS OF GRAFT FUNCTION" @default.
- W1986425314 doi "https://doi.org/10.1097/00007890-199904150-00460" @default.
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