X-ray imaging of differential vascular density in MMP-9−/−, PAR-1−/+, hyperhomocysteinemic (CBS−/+) and diabetic (Ins2−/+) mice

Givvimani, Srikanth; Sen, Utpal; Tyagi, Neetu; Munjal, Charu; Tyagi, Suresh C.

doi:10.3109/13813455.2010.512042

Cited by 20 publications

(14 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our group has previously been exploited this technique to elucidate vascular heterogeneity in Akita and other experimental murine models [52]. Using the same sophisticated method for assessing vasculature we also reported that reduction in arcuate and interlobular renal arteries occurred in Timp-2 −/− animals [12].…”

Section: Discussionmentioning

confidence: 99%

MMP-9- and NMDA receptor-mediated mechanism of diabetic renovascular remodeling and kidney dysfunction: Hydrogen sulfide is a key modulator

2015

View full text Add to dashboard Cite

Previously we reported that matrix metalloproteinase-9 (MMP-9) plays an important role in extracellular matrix (ECM) remodeling in diabetic kidney. Induction of NMDA-R and dysregulation of connexins (Cxs) were also observed. We concluded that this was due to decreased H2S production by down regulation of CBS and CSE enzymes. However, the potential role of H2S to mitigate ECM dysregulation and renal dysfunction was not clearly understood. The present study was undertaken to determine whether H2S supplementation reduces MMP-9-induced ECM remodeling and dysfunction in diabetic kidney. Wild type (C57BL/6J), diabetic (Akita, C57BL/6J-Ins2Akita), MMP-9 knockout (MMP-9−/− , M9KO) and double KO of Akita/MMP-9−/− (DKO) mice were treated without or with 0.05 g/L of NaHS (as a source of H2S) in drinking water for 30 days. Decreased tissue production and plasma content of H2S in Akita mice were ameliorated with H2S supplementation. Dysregulated expression of MMP-9, CBS, CSE, NMDA-R1 and Cxs-40, -43 were also normalized in Akita mice treated with H2S. In addition, increased renovascular resistive index (RI), ECM deposition, plasma creatinine, and diminished renal vascular density and cortical blood flow in Akita mice were normalized with H2S treatment. We conclude that diminished H2S production in renal tissue and plasma levels in diabetes mediates adverse renal remodeling, and H2S therapy improves renal function through MMP-9- and NMDA-R1-mediated pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

MMP-9- and NMDA receptor-mediated mechanism of diabetic renovascular remodeling and kidney dysfunction: Hydrogen sulfide is a key modulator

2015

View full text Add to dashboard Cite

show abstract

“…Barium sulphate was dissolved in 50 mM Tris-buffer (pH 5.0) and infused slowly at a constant flow and pressure with a syringe pump using carotid artery (Myojin et al, 2007; Givvimani et al, 2011). This produced the optimal visualization of vascular density in brain.…”

Section: Methodsmentioning

confidence: 99%

Hydrogen sulfide attenuates neurodegeneration and neurovascular dysfunction induced by intracerebral-administered homocysteine in mice

et al. 2013

Self Cite

View full text Add to dashboard Cite

High levels of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy) are associated with neurovascular diseases. H2S, a metabolite of Hcy, has a potent anti-oxidant and anti-inflammatory activity; however, the effect of H2S has not been explored in Hcy (IC) induced neurodegeneration and neurovascular dysfunction in mice. Therefore, the present study was designed to explore the neuroprotective role of H2S on Hcy induced neurodegeneration and neurovascular dysfunction. To test this hypothesis we employed wild type (WT) males ages 8–10 weeks, WT+ artificial cerebrospinal fluid (aCSF), WT+ Hcy (0.5μmol/μl) intracerebral injection (I.C., one time only prior to NaHS treatment), WT+Hcy +NaHS (sodium hydrogen sulfide, precursor of H2S, 30 μmol/kg, body weight). NaHS was injected intra-peritoneally (I.P.) once daily for the period of 7 days after the Hcy (IC) injection. Hcy treatment significantly increased MDA, nitrite level, acetylcholinestrase activity, TNFα, IL1β, GFAP, iNOS, eNOS and decreased glutathione level indicating oxidative-nitrosative stress and neuroinflammation as compared to control and aCSF treated groups. Further, increased expression of NSE, S100B and decreased expression of (PSD95, SAP97) synaptic protein indicated neurodegeneration. Brain sections of Hcy treated mice showed damage in the cortical area and periventricular cells. TUNEL positive cells and Fluro Jade-C staining indicated apoptosis and neurodegeneration. The increased expression of MMP9, MMP2 and decreased expression of TIMP-1, TIMP-2, tight junction proteins (ZO1, Occuldin) in Hcy treated group indicate neurovascular remodeling. Interestingly, NaHS treatment significantly attenuated Hcy induced oxidative stress, memory deficit, neurodegeneration, neuroinflammation and cerebrovascular remodeling. The results indicate that H2S is effective in providing protection against neurodegeneration and neurovascular dysfunction.

show abstract

“…Barium sulfate is toxic if enters in to circulation system. We used barium sulfate for tibia imaging of mice vasculature 12. All images were taken with Kodak 4000 MM image station.…”

Section: Methodsmentioning

confidence: 99%

Homocysteine mediated decrease in bone blood flow and remodeling: Role of folic acid

Tyagi

Kandel

Munjal

et al. 2011

Journal Orthopaedic Research

View full text Add to dashboard Cite

Deficiencies in folate lead to increased serum concentrations of homocysteine (Hcy), which is known as hyperhomocysteinemia (HHcy), is associated with bone disorders. Although, homocysteine (Hcy) accumulates collagen in bone and contribute to decrease in bone strength. The mechanism of Hcy induced bone loss and remodeling is unclear. Therefore, the present study was aimed to determine the role of folic acid in genetically HHcy associated decrease in bone blood flow and remodeling. Wildtype (WT) and cystathionine-β-synthase heterozygous (CBS+/−) mice were used in this study and supplemented with or without folic acid (FA 300 mg/kg, Hcy reducing agent) in drinking water for 6 weeks. The tibial bone blood flow was measured by laser Doppler and ultrasonic flow probe method. The tibial bone density was assessed by dual energy X-ray absorptiometry. The bone homogenates were analyzed for oxidative stress,NOX-4 as oxidative marker and thioredoxin-1 (Trx-1) as anti-oxidant marker, bone remodeling (MMP-9) and bio-availability of nitric oxide (eNOS/iNOS/NO) by Western blot method. The results suggested that there was decrease in tibial blood flow in CBS+/− mice. The bone density was also reduced in CBS+/− mice. There was an increase in NOX-4, iNOS, MMP -9 protein as well as MMP-9 activity in CBS+/− mice and decrease in Trx-1, eNOS protein levels, in part by decreasing NO bio-availability in CBS+/− mice. Interestingly, these effects were ameliorated by folic acid and suggested that folic acid supplementation may have therapeutic potential against genetically HHcy induced bone loss.

show abstract

X-ray imaging of differential vascular density in MMP-9−/−, PAR-1−/+, hyperhomocysteinemic (CBS−/+) and diabetic (Ins2−/+) mice

Cited by 20 publications

References 24 publications

MMP-9- and NMDA receptor-mediated mechanism of diabetic renovascular remodeling and kidney dysfunction: Hydrogen sulfide is a key modulator

MMP-9- and NMDA receptor-mediated mechanism of diabetic renovascular remodeling and kidney dysfunction: Hydrogen sulfide is a key modulator

Hydrogen sulfide attenuates neurodegeneration and neurovascular dysfunction induced by intracerebral-administered homocysteine in mice

Homocysteine mediated decrease in bone blood flow and remodeling: Role of folic acid

Contact Info

Product

Resources

About