scholarly journals N-acetyl-seryl-aspartyl-lysyl-proline reduces cardiac collagen cross-linking and inflammation in angiotensin II-induced hypertensive rats

2013 ◽  
Vol 126 (1) ◽  
pp. 85-94 ◽  
Author(s):  
Germán E. González ◽  
Nour-Eddine Rhaleb ◽  
Pablo Nakagawa ◽  
Tang-Dong Liao ◽  
Yunhe Liu ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Lysyl Oxidase ◽  
Left Ventricular ◽  
Cross Linking ◽  
Lymphocyte Infiltration ◽  
Total Collagen ◽  
Induced Hypertension ◽  
Collagen Cross Linking

We have reported previously that Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline) reduces fibrosis and inflammation (in macrophages and mast cells). However, it is not known whether Ac-SDKP decreases collagen cross-linking and lymphocyte infiltration; lymphocytes modulate both collagen cross-linking and ECM (extracellular matrix) formation in hypertension. Thus we hypothesized that (i) in AngII (angiotensin II)-induced hypertension, Ac-SDKP prevents increases in cross-linked and total collagen by down-regulating LOX (lysyl oxidase), the enzyme responsible for cross-linking, and (ii) these effects are associated with decreased pro-fibrotic cytokine TGFβ (transforming growth factor β) and the pro-inflammatory transcription factor NF-κB (nuclear factor κB) and CD4+/CD8+ lymphocyte infiltration. We induced hypertension in rats by infusing AngII either alone or combined with Ac-SDKP for 3 weeks. Whereas Ac-SDKP failed to lower BP (blood pressure) or LV (left ventricular) hypertrophy, it did prevent AngII-induced increases in (i) cross-linked and total collagen, (ii) LOX mRNA expression and LOXL1 (LOX-like 1) protein, (iii) TGFβ expression, (iv) nuclear translocation of NF-κB, (v) CD4+/CD8+ lymphocyte infiltration, and (vi) CD68+ macrophages infiltration. In addition, we found a positive correlation between CD4+ infiltration and LOXL1 expression. In conclusion, the effect of Ac-SDKP on collagen cross-linking and total collagen may be due to reduced TGFβ1, LOXL1, and lymphocyte and macrophage infiltration, and its effect on inflammation could be due to lower NF-κB.

scholarly journals Genistein Prevents Nitric Oxide Deficiency-Induced Cardiac Dysfunction and Remodeling in Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 237 ◽  
Author(s):  
Anuson Poasakate ◽  
Putcharawipa Maneesai ◽  
Siwayu Rattanakanokchai ◽  
Sarawoot Bunbupha ◽  
Terdthai Tong-Un ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Treated Group ◽  
Left Ventricular ◽  
Type I ◽  
Hypertensive Rats ◽  
Induced Hypertension ◽  
Tgf Β1

Genistein is an isoflavone found in soybeans. This study evaluates the protective effects of genistein on Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertension, cardiac remodeling, and dysfunction in rats. Male Wistar rats were treated with L-NAME 40 mg/kg/day together for 5 weeks, with or without genistein at a dose of 40 or 80 mg/kg/day or lisinopril 5 mg/kg/day (n = 8 per group). Genistein prevented L-NAME-induced hypertension in rats. Increases in the left ventricular weight, metalloproteinase-2, metalloproteinase-9, and collagen type I intensity were observed in L-NAME rats, and these changes were attenuated in the genistein-treated group. Genistein reduced circulating angiotensin-converting enzyme activity and angiotensin II concentrations in L-NAME rats. L-NAME increased plasma and cardiac malondialdehyde and vascular superoxide generations, as well as reductions of serum and cardiac catalase activities in rats. Plasma nitrate/nitrite were protected in the genistein-treated group. Genistein prevented the L-NAME-induced overexpression of angiotensin II receptor type I (AT1R), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit 2 (gp91phox), and transforming growth factor beta I (TGF-β1) in hypertensive rats. In conclusion, genistein exhibited a cardioprotective effect in hypertensive rats in this study. The molecular mechanisms might be mediated by suppression of oxidative stress through the Ang II/AT1R/NADPH oxidase/TGF-β1 signaling pathway.

scholarly journals Impact of Treatment on Myocardial Lysyl Oxidase Expression and Collagen Cross-Linking in Patients With Heart Failure

Hypertension ◽  
2009 ◽  
Vol 53 (2) ◽  
pp. 236-242 ◽  
Author(s):  
Begoña López ◽  
Ramón Querejeta ◽  
Arantxa González ◽  
Javier Beaumont ◽  
Mariano Larman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Lysyl Oxidase ◽  
Cross Linking ◽  
Patients With Heart Failure ◽  
Collagen Cross Linking

Collagen cross-linking: Lysyl oxidase dependent synthesis of pyridinoline in vitro: Confirmation that pyridinoline is derived from collagen

1982 ◽  
Vol 108 (4) ◽  
pp. 1546-1550 ◽  
Author(s):  
Robert C. Siegel ◽  
Joseph C.C. Fu ◽  
Norihiko Uto ◽  
Kentaro Horiuchi ◽  
Daisaburo Fujimoto
Keyword(s):  
Lysyl Oxidase ◽  
Cross Linking ◽  
Collagen Cross Linking

Enalapril decreases cardiac mass and fetal gene expression without affecting the expression of endothelin-1, transforming growth factor β-1, or cardiotrophin-1 in the healthy normotensive rat

2011 ◽  
Vol 89 (3) ◽  
pp. 197-205 ◽  
Author(s):  
Katarina Mackovicova ◽  
Andrea Gazova ◽  
Dana Kucerova ◽  
Beata Gajdacova ◽  
Jan Klimas ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Growth Factors ◽  
Angiotensin Ii ◽  
Growth Factor ◽  
Cardiac Hypertrophy ◽  
Left Ventricular Mass ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Left Ventricular ◽  
Ventricular Mass

Angiotensin II can induce cardiac hypertrophy by stimulating the release of growth factors. ACE inhibitors reduce angiotensin II levels and cardiac hypertrophy, but their effects on the healthy heart are largely unexplored. We hypothesized that ACE inhibition decreases left ventricular mass in normotensive animals and that this is associated with altered expression of cardiac fetal genes, growth factors, and endothelial nitric oxide synthase (eNOS). Wistar rats (n = 7 per group) were orally administered with enalapril twice daily for a total daily dose of 5 mg·kg–1·d–1 (ENAP5) or 15 mg·kg–1·d–1 (ENAP15) or vehicle. Systolic blood pressure was measured by the tail-cuff method. Left ventricular expression of cardiac myosin heavy chain-α (MYH6) and -β (MYH7), atrial natriuretic peptide (ANP), endothelin-1 (ET-1), transforming growth factor β-1 (TGFβ-1), cardiotrophin-1 (CT-1), and renal renin were examined by real-time PCR, and eNOS using Western blot. Blood pressure was decreased only in ENAP15 animals (p < 0.05 vs. Control), whereas left ventricular mass decreased after both doses of enalapril (p < 0.05 vs. Control). MYH7 and ANP were reduced in ENAP15, while no changes in ET-1, TGFβ-1, CT-1, and MYH6 mRNA or eNOS protein were observed. Renal renin dose-dependently increased after enalapril treatment. Enalapril significantly decreased left ventricular mass even after 1 week treatment in the normotensive rat. This was associated with a decreased expression of the fetal genes MYH7 and ANP, but not expression of ET-1, CT-1, or TGFβ-1.

scholarly journals The collagen cross‐linking enzyme lysyl oxidase is associated with the healing of human atherosclerotic lesions

2014 ◽  
Vol 276 (5) ◽  
pp. 525-536 ◽  
Author(s):  
O. A. Ovchinnikova ◽  
L. Folkersen ◽  
J. Persson ◽  
J. H. N. Lindeman ◽  
T. Ueland ◽  
...  
Keyword(s):  
Lysyl Oxidase ◽  
Cross Linking ◽  
Atherosclerotic Lesions ◽  
Collagen Cross Linking

scholarly journals Moderate Loss of the Extracellular Matrix Proteoglycan Lumican Attenuates Cardiac Fibrosis in Mice Subjected to Pressure Overload

Cardiology ◽  
2020 ◽  
Vol 145 (3) ◽  
pp. 187-198 ◽  
Author(s):  
Naiyereh Mohammadzadeh ◽  
Arne Olav Melleby ◽  
Sheryl Palmero ◽  
Ivar Sjaastad ◽  
Shukti Chakravarti ◽  
...  
Keyword(s):  
Heart Failure ◽  
Extracellular Matrix ◽  
Diastolic Dysfunction ◽  
Cardiac Fibrosis ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Cross Linking ◽  
Myocardial Remodeling ◽  
Functional Changes ◽  
Collagen Cross Linking

Introduction: The heart undergoes myocardial remodeling during progression to heart failure following pressure overload. Myocardial remodeling is associated with structural and functional changes in cardiac myocytes, fibroblasts, and the extracellular matrix (ECM) and is accompanied by inflammation. Cardiac fibrosis, the accumulation of ECM molecules including collagens and collagen cross-linking, contributes both to impaired systolic and diastolic function. Insufficient mechanistic insight into what regulates cardiac fibrosis during pathological conditions has hampered therapeutic so­lutions. Lumican (LUM) is an ECM-secreted proteoglycan known to regulate collagen fibrillogenesis. Its expression in the heart is increased in clinical and experimental heart failure. Furthermore, LUM is important for survival and cardiac remodeling following pressure overload. We have recently reported that total lack of LUM increased mortality and left ventricular dilatation, and reduced collagen expression and cross-linking in LUM knockout mice after aortic banding (AB). Here, we examined the effect of LUM on myocardial remodeling and function following pressure overload in a less extreme mouse model, where cardiac LUM level was reduced to 50% (i.e., moderate loss of LUM). Methods and Results: mRNA and protein levels of LUM were reduced to 50% in heterozygous LUM (LUM+/–) hearts compared to wild-type (WT) controls. LUM+/– mice were subjected to AB. There was no difference in survival between LUM+/– and WT mice post-AB. Echocardiography revealed no striking differences in cardiac geometry between LUM+/– and WT mice 2, 4, and 6 weeks post-AB, although markers of diastolic dysfunction indicated better function in LUM+/– mice. LUM+/– hearts revealed reduced cardiac fibrosis assessed by histology. In accordance, the expression of collagen I and III, the main fibrillar collagens in the heart, and other ECM molecules central to fibrosis, i.e. including periostin and fibronectin, was reduced in the hearts of LUM+/– compared to WT 6 weeks post-AB. We found no differences in collagen cross-linking between LUM+/– and WT mice post-AB, as assessed by histology and qPCR. Conclusions: Moderate lack of LUM attenuated cardiac fibrosis and improved diastolic dysfunction following pressure overload in mice, adding to the growing body of evidence suggesting that LUM is a central profibrotic molecule in the heart that could serve as a potential therapeutic target.

scholarly journals Phosphorylation of GATA4 at serine 105 is required for left ventricular remodelling process in angiotensin II‐induced hypertension in rats

2020 ◽  
Vol 127 (3) ◽  
pp. 178-195
Author(s):  
Alicia Jurado Acosta ◽  
Jaana Rysä ◽  
Zoltan Szabo ◽  
Anne‐Mari Moilanen ◽  
Raisa Serpi ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Left Ventricular ◽  
Ventricular Remodelling ◽  
Left Ventricular Remodelling ◽  
Induced Hypertension

Abstract 101: Cardiac Deleterious Role of Galectin-3 in Chronic Angiotensin-II Induced Hypertension

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Germán E González ◽  
Nour-Eddine Rhaleb ◽  
Xiao- P Yang ◽  
Oscar A Carretero
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Cardiac Fibrosis ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Carbohydrate Binding ◽  
Ang Ii ◽  
Induced Hypertension ◽  
Galectin 3

We previously described that chronic infusion with Angiotensin II (Ang II) increases cardiac Galectin-3 (Gal-3) expression, a carbohydrate-binding lectin present on macrophages. Also, Gal-3 was proposed to be a powerful predictor for mortality in patients with heart failure. Nevertheless, the role of Gal-3 in the pathogenesis of end organ damage (EOD) in hypertension is unknown. Here, we hypothesized that in Ang II-induced hypertension, genetic deletion of Gal-3 prevents innate immunity, EOD, and left ventricular (LV) dysfunction. Male C57 and Gal-3 KO mice were infused with vehicle (V) or Ang II (90 ng/min; s.c.) for 8 weeks and divided into: 1) C57 + V; 2) Gal-3 KO + V; 3) C57 + Ang II and 4) Gal-3 KO + Ang II. Systolic blood pressure (SBP) was measured by plestimography weekly. At 8 week, we evaluated 1) LV ejection fraction (EF) by echocardiography; 2) cardiac hypertrophy by LV weight/tibia length; 3) cardiac fibrosis by picrosirius red staining; 4) infiltrated macrophages by CD68+ staining; 5) ICAM-1 protein expression by Western blot; and 6) serum interleukin (IL)-6 by ELISA. We found that despite a similar increase in SBP and LV hypertrophy in both strains on Ang II, Gal-3 KO mice had better reserved EF and decreased inflammatory and fibrotic responses (see Table). Results: (MEAN ± SEM at 8 w) *p<0.05 C57+Ang II and Gal-3 KO+Ang II vs C57+V; ‡ p<0.05 Gal-3 KO+Ang II vs C57+Ang II. Conclusion: In Ang II-induced hypertension, deletion of Gal-3 prevents EOD and LV systolic dysfunction without altering blood pressure and LV hypertrophy. This study indicates that the deleterious effects of Ang II could be in part mediated by Gal-3, which enhanced inflammation and fibrosis.

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