scholarly journals Matrix metalloproteinase in the cardiovascular remodeling of hypertension: current insights and therapeutic potential

2018 ◽  
Vol Volume 5 ◽  
pp. 1-11 ◽  
Author(s):  
Juliana Parente ◽  
Michele de Castro
Keyword(s):  
Matrix Metalloproteinase ◽  
Therapeutic Potential ◽  
Cardiovascular Remodeling

scholarly journals Therapeutic Potential of the Molecular Chaperone and Matrix Metalloproteinase Inhibitor Clusterin for Dry Eye

2020 ◽  
Vol 22 (1) ◽  
pp. 116
Author(s):  
M. Elizabeth Fini ◽  
Shinwu Jeong ◽  
Mark R. Wilson
Keyword(s):  
Epithelial Cell ◽  
Matrix Metalloproteinase ◽  
Dry Eye ◽  
Molecular Chaperone ◽  
Ocular Surface ◽  
Therapeutic Potential ◽  
Autoimmune Response ◽  
Interacting Protein ◽  
Bodily Fluids ◽  
Epithelial Cell Layer

Evidence is presented herein supporting the potential of the natural homeostatic glycoprotein CLU (clusterin) as a novel therapeutic for the treatment of dry eye. This idea began with the demonstration that matrix metalloproteinase MMP9 is required for damage to the ocular surface in mouse dry eye. Damage was characterized by degradation of OCLN (occludin), a known substrate of MMP9 and a key component of the paracellular barrier. Following up on this finding, a yeast two-hybrid screen was conducted using MMP9 as the bait to identify other proteins involved. CLU emerged as a strong interacting protein that inhibits the enzymatic activity of MMP9. Previously characterized as a molecular chaperone, CLU is expressed prominently by epithelia at fluid-tissue interfaces and secreted into bodily fluids, where it protects cells and tissues against damaging stress. It was demonstrated that CLU also protects the ocular surface in mouse dry eye when applied topically to replace the natural protein depleted from the dysfunctional tears. CLU is similarly depleted from tears in human dry eye. The most novel and interesting finding was that CLU binds selectively to the damaged ocular surface. In this position, CLU protects against epithelial cell death and barrier proteolysis, and dampens the autoimmune response, while the apical epithelial cell layer is renewed. When present at high enough concentration, CLU also blocks staining by vital dyes used clinically to diagnose dry eye. None of the current therapeutics have this combination of properties to “protect, seal, and heal”. Future work will be directed towards human clinical trials to investigate the therapeutic promise of CLU.

scholarly journals Hesperidin Prevents Nitric Oxide Deficiency-Induced Cardiovascular Remodeling in Rats via Suppressing TGF-β1 and MMPs Protein Expression

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1549 ◽  
Author(s):  
Putcharawipa Maneesai ◽  
Sarawoot Bunbupha ◽  
Prapassorn Potue ◽  
Thewarid Berkban ◽  
Upa Kukongviriyapan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Tumor Necrosis Factor ◽  
Matrix Metalloproteinase ◽  
Protein Expression ◽  
Wall Thickness ◽  
Tumor Necrosis ◽  
Left Ventricular ◽  
Cardiovascular Remodeling ◽  
Tgf Β1 ◽  
Necrosis Factor

Hesperidin is a major flavonoid isolated from citrus fruits that exhibits several biological activities. This study aims to evaluate the effect of hesperidin on cardiovascular remodeling induced by n-nitro l-arginine methyl ester (l-NAME) in rats. Male Sprague-Dawley rats were treated with l-NAME (40 mg/kg), l-NAME plus hesperidin (15 mg/kg), hesperidin (30 mg/kg), or captopril (2.5 mg/kg) for five weeks (n = 8/group). Hesperidin or captopril significantly prevented the development of hypertension in l-NAME rats. l-NAME-induced cardiac remodeling, i.e., increases in wall thickness, cross-sectional area (CSA), and fibrosis in the left ventricular and vascular remodeling, i.e., increases in wall thickness, CSA, vascular smooth muscle cells, and collagen deposition in the aorta were attenuated by hesperidin or captopril. These were associated with reduced oxidative stress markers, tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta 1 (TGF-β1), and enhancing plasma nitric oxide metabolite (NOx) in l-NAME treated groups. Furthermore, up-regulation of tumor necrosis factor receptor type 1 (TNF-R1) and TGF- β1 protein expression and the overexpression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) was suppressed in l-NAME rats treated with hesperidin or captopril. These data suggested that hesperidin had cardioprotective effects in l-NAME hypertensive rats. The possible mechanism may involve antioxidant and anti-inflammatory effects.

scholarly journals Hesperidin Prevents Nitric Oxide Deficiency-Induced Cardiovascular Remodeling in Rats via Suppressing TGF-β1 and MMPs Protein Expression

2018 ◽  
Author(s):  
Putcharawipa Maneesai ◽  
Sarawoot Bunbupha ◽  
Prapassorn Potue ◽  
Thewarid Berkban ◽  
Upa Kukongviriyapan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Tumor Necrosis Factor ◽  
Matrix Metalloproteinase ◽  
Protein Expression ◽  
Wall Thickness ◽  
Tumor Necrosis ◽  
Left Ventricular ◽  
Matrix Metalloproteinase 2 ◽  
Cardiovascular Remodeling ◽  
Necrosis Factor

Hesperidin is a major flavonoid isolated from citrus fruits that exhibits several biological activities. This study aims to evaluate the effect of hesperidin on cardiovascular remodeling induced by N-nitro L-arginine methyl ester (L-NAME) in rats.  Male Sprague-Dawley rats were treated with L-NAME (40 mg/kg); L-NAME plus hesperidin (15 mg/kg), or hesperidin (30 mg/kg), or captopril (2.5 mg/kg) for five weeks (n = 8/group). Hesperidin or captopril significantly prevented the development of hypertension in L-NAME rats.  Moreover, hesperidin or captopril alleviated L-NAME-induced cardiac remodeling; increases in wall thickness, cross sectional area (CSA) and fibrosis of left ventricular (LV), and vascular remodeling; increases in wall thickness, CSA, vascular smooth muscle cells and collagen deposition in the aorta. These were associated with reduced oxidative stress markers, tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta 1 (TGF-β1) and enhancing plasma nitric oxide metabolite (NOx) in L-NAME treated groups. Furthermore, up-regulation of tumor necrosis factor receptor type 1 (TNF-R1) and TGF-β1 protein expression and the over-expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were suppressed in L-NAME rats treated with hesperidin or captopril. These data suggested that hesperidin had cardioprotective effects in L-NAME hypertensive rats. The possible mechanism may involve its antioxidant and anti-inflammatory effects.

scholarly journals Hydrogen sulfide deficiency and diabetic renal remodeling: role of matrix metalloproteinase-9

2013 ◽  
Vol 304 (12) ◽  
pp. E1365-E1378 ◽  
Author(s):  
Sourav Kundu ◽  
Sathnur B. Pushpakumar ◽  
Aaron Tyagi ◽  
Denise Coley ◽  
Utpal Sen
Keyword(s):  
Hydrogen Sulfide ◽  
Matrix Metalloproteinase ◽  
Therapeutic Potential ◽  
Matrix Metalloproteinase 9 ◽  
Double Knockout ◽  
Diabetic Kidney ◽  
Connexin 40 ◽  
Akita Mice ◽  
Metalloproteinase 9

Matrix metalloproteinase-9 (MMP-9) causes adverse remodeling, whereas hydrogen sulfide (H2S) rescues organs in vascular diseases. The involvement of MMP-9 and H2S in diabetic renovascular remodeling is, however, not well characterized. We determined whether MMP-9 regulates H2S generation and whether H2S modulates connexin through N-methyl-d-aspartate receptor (NMDA-R)-mediated pathway in the diabetic kidney. Wild-type (WT, C57BL/6J), diabetic (Akita, C57BL/6J- Ins2 Akita), MMP-9−/− (M9KO), double knockout (DKO) of Akita/MMP-9−/− mice and in vitro cell culture were used in our study. Hyperglycemic Akita mice exhibited increased level of MMP-9 and decreased production of H2S. H2S-synthesizing enzymes cystathionine-β-synthase and cystathionine-γ-lyase were also diminished. In addition, increased expressions of NMDA-R1 and connexin-40 and -43 were observed in diabetic kidney. As expected, MMP-9 mRNA was not detected in M9KO kidneys. However, very thin protein expression and activity were detected. No other changes were noticed in M9KO kidney. In DKO mice, all the above molecules showed a trend toward baseline despite hyperglycemia. In vitro, glomerular endothelial cells treated with high glucose showed induction of MMP-9, attenuated H2S production, NMDA-R1 induction, and dysregulated conexin-40 and -43 expressions. Silencing MMP-9 by siRNA or inhibition of NMDA-R1 by MK801 or H2S treatment preserved connexin-40 and -43. We conclude that in diabetic renovascular remodeling MMP-9 plays a major role and that H2S has therapeutic potential to prevent adverse diabetic renal remodeling.

scholarly journals Curcumin reduces prostaglandin E2, matrix metalloproteinase-3 and proteoglycan release in the secretome of interleukin 1β-treated articular cartilage

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 147 ◽  
Author(s):  
Abigail L Clutterbuck ◽  
David Allaway ◽  
Pat Harris ◽  
Ali Mobasheri
Keyword(s):  
Articular Cartilage ◽  
Matrix Metalloproteinase ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Primary Cultures ◽  
Cartilage Explants ◽  
Prostaglandin E ◽  
Primary Chondrocytes ◽  
Chondrocyte Death ◽  
Anti Inflammatory

Objective: Curcumin (diferuloylmethane) is a phytochemical with potent anti-inflammatory and anti-oxidant properties, and has therapeutic potential for the treatment of a range of inflammatory diseases, including osteoarthritis (OA). The aim of this study was to determine whether non-toxic concentrations of curcumin can reduce interleukin-1beta (IL-1β)-stimulated inflammation and catabolism in an explant model of cartilage inflammation.Methods: Articular cartilage explants and primary chondrocytes were obtained from equine metacarpophalangeal joints. Curcumin was added to monolayer cultured primary chondrocytes and cartilage explants in concentrations ranging from 3μM-100μM. Prostaglandin E2 (PGE2) and matrix metalloproteinase (MMP)-3 release into the secretome of IL-1β-stimulated explants was measured using a competitive ELISA and western blotting respectively. Proteoglycan (PG) release in the secretome was measured using the 1,9-dimethylmethylene blue (DMMB) assay. Cytotoxicity was assessed with a live/dead assay in monolayer cultures after 24 hours, 48 hours and five days, and in explants after five days.Results: Curcumin induced chondrocyte death in primary cultures (50μM p<0.001 and 100μM p<0.001) after 24 hours. After 48 hours and five days, curcumin (≥25μM) significantly increased cell death (p<0.001 both time points). In explants, curcumin toxicity was not observed at concentrations up to and including 25μM after five days. Curcumin (≥3μM) significantly reduced IL-1β-stimulated PG (p<0.05) and PGE2 release (p<0.001) from explants, whilst curcumin (≥12μM) significantly reduced MMP-3 release (p<0.01).Conclusion: Non-cytotoxic concentrations of curcumin exert anti-catabolic and anti-inflammatory effects in cartilage explants.

scholarly journals Curcumin reduces prostaglandin E2, matrix metalloproteinase-3 and proteoglycan release in the secretome of interleukin 1β-treated articular cartilage

F1000Research ◽  
2013 ◽  
Vol 2 ◽  
pp. 147 ◽  
Author(s):  
Abigail L Clutterbuck ◽  
David Allaway ◽  
Pat Harris ◽  
Ali Mobasheri
Keyword(s):  
Articular Cartilage ◽  
Matrix Metalloproteinase ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Primary Cultures ◽  
Cartilage Explants ◽  
Prostaglandin E ◽  
Primary Chondrocytes ◽  
Chondrocyte Death ◽  
Anti Inflammatory

Objective: Curcumin (diferuloylmethane) is a phytochemical with potent anti-inflammatory and anti-oxidant properties, and has therapeutic potential for the treatment of a range of inflammatory diseases, including osteoarthritis (OA). The aim of this study was to determine whether non-toxic concentrations of curcumin can reduce interleukin-1beta (IL-1β)-stimulated inflammation and catabolism in an explant model of cartilage inflammation.Methods: Articular cartilage explants and primary chondrocytes were obtained from equine metacarpophalangeal joints. Curcumin was added to monolayer cultured primary chondrocytes and cartilage explants in concentrations ranging from 3μM-100μM. Prostaglandin E2 (PGE2) and matrix metalloproteinase (MMP)-3 release into the secretome of IL-1β-stimulated explants was measured using a competitive ELISA and western blotting respectively. Proteoglycan (PG) release in the secretome was measured using the 1,9-dimethylmethylene blue (DMMB) assay. Cytotoxicity was assessed with a live/dead assay in monolayer cultures after 24 hours, 48 hours and five days, and in explants after five days.Results: Curcumin induced chondrocyte death in primary cultures (50μM p<0.001 and 100μM p<0.001) after 24 hours. After 48 hours and five days, curcumin (≥25μM) significantly increased cell death (p<0.001 both time points). In explants, curcumin toxicity was not observed at concentrations up to and including 25μM after five days. Curcumin (≥3μM) significantly reduced IL-1β-stimulated PG (p<0.05) and PGE2 release (p<0.001) from explants, whilst curcumin (≥12μM) significantly reduced MMP-3 release (p<0.01).Conclusion: Non-cytotoxic concentrations of curcumin exert anti-catabolic and anti-inflammatory effects in cartilage explants.

Statins for the prevention of vein graft stenosis: a role for inhibition of matrix metalloproteinase-9

2002 ◽  
Vol 30 (2) ◽  
pp. 120-126 ◽  
Author(s):  
K. E. Porter ◽  
N. A. Turner
Keyword(s):  
Matrix Metalloproteinase ◽  
Intimal Hyperplasia ◽  
Therapeutic Potential ◽  
Matrix Metalloproteinase 2 ◽  
Neointima Formation ◽  
Graft Stenosis ◽  
The Matrix ◽  
And Migration ◽  
Proliferation And Migration

Saphenous vein (SV) grafts are commonly used to bypass coronary arteries that are diseased due to atherosclerosis. However, the development of intimal hyperplasia in such grafts can lead to patency-threatening stenosis and re-occlusion of the vessel. The proliferation and migration of smooth muscle cells (SMC) play key roles in the development of intimal hyperplasia, and an agent that inhibits both of these processes therefore has therapeutic potential. A prerequisite for SMC proliferation and migration in vivo is degradation of the basement membrane, achieved by secretion of the matrix-degrading gelatinases matrix metalloproteinase-2 (MMP-2) and MMP-9. Statins are cholesterol-lowering drugs that also have direct effects on SMC function. Here we report that neointima formation in organ-cultured human SV segments is inhibited by simvastatin, an effect that is associated with reduced MMP-9 activity. Additionally, our work shows that simvastatin not only inhibits proliferation, but importantly also inhibits invasion (migration through a matrix barrier), of cultured human SV SMC. Thus simvastatin treatment appears to inhibit neointima formation as a result of combined inhibition of SMC proliferation and invasion. The potential intracellular mechanisms by which statins affect SMC proliferation and migration, and thus attenuate intimal hyperplasia, are discussed, with particular emphasis on the role of MMP-9.

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