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AcSDKP Reduces Collagen Crosslinking, MMP and NFKB Expression in Angiotensin II Induced Hypertension
Author(s) -
Gonzalez German Esteban,
Nakagawa Pablo,
Liu Yunhe,
Liao TangDong,
Yang XiaoPing,
Rhaleb NourEddine,
Carretero Oscar A.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb572
Subject(s) - chemistry , matrix metalloproteinase , angiotensin ii , medicine , endocrinology , myocardial fibrosis , mmp2 , cardiac fibrosis , renin–angiotensin system , fibrosis , downregulation and upregulation , blood pressure , biochemistry , gene
We hypothesized that N‐acetyl‐Ser‐Asp‐Lys‐Pro AcSDKP not only reduces fibrosis but also crosslinking. Moreover we tested whether it increases MMP, which has antifibrotic effects and whether it reduces NFκB in the heart. Lewis rats were divided in 4 groups (n=6, each): 1 (control); 2 (AngII 750…g/kg/day); 3 (AcSDKP 800…g/kg/day); and 4 (AngII+AcSDKP). Systolic blood pressure (mmHg) was recorded for 3 weeks. After 3 weeks crosslinking was quantified by measuring total (TC), insoluble (IC) and soluble (SC) collagen (μg/mg dry weight tissue) and MMP2 activity (% respect to 1) in cardiac tissue. NFκB activity was quantified (EMSA assay). Results (X±SEM)Control AngII AcSDKP AcSDKP+AngIIBP 125±3 202±15 * 122±3 205±8 * TC 11.7±1.3 19.0±1.8 * 12.5±1.5 13.0±0.9 # IC 9.5±1.3 16.3±1.6 * 10.7±1.3 10.0±0.9 # SC 2.0±0.2 2.7±0.7 1.7±0.4 2.9±0.7 MMP2 100.0±19.2 101.9±13.0 74.9±13.1 139.6±19.5 † NFκB 11.5±1.4 24.4±1.8 * 15.0±3.5 15.7±2.0 #* and # p<.05 vs G1 and 2 respectively;† p=.094vsG2Conclusion AcSDKP decreased crosslinked collagen which is important for reducing myocardial stiffness in hypertension. MMP2 activity tends to increase, and may have a small role in the antifibrotic effect of AcSDKP. Also, AcSDKP decreased NFκB suggesting that its antiinflammatory effect may be mediated by reducing this factor. Grant#: NIH HL028982 to OAC