Suresh C Tyagi

..In addition Hcy competes with PPAR ligands. The understanding of molecular, cellular, and extracellular mechanisms by which Hcy amplifies DM will have therapeutic ramifications for diabetic cardiomyopathy...

..In conclusion, our data suggest that copper supplement helps improve cardiac function in a pressure overload dilated cardiomyopathic heart...

..Furthermore muscimol attenuated Hcy-induced MMP-9 via ERK signaling pathway. These results suggest that Hcy competes with GABA-A receptors, inducing the oxidative stress transduction pathway and leading to ERK activation...

..CZ, however, protected diabetic nephropathy in part by activating PPARgamma and clearing glomerular tissue Hcy...

..These results suggested that Hcy caused arterial remodeling in part, by increase in collagen/elastin ratio thereby increasing VR leading to the decrease in CA blood flow...

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..We summarize that chronic HHcy causes vascular remodelling that transduces changes in vascular wall in a way that artery expresses vein phenotype...

..Sodium thiosulfate (STS) has been shown to be an antioxidant and calcium solubilizer, but the possible role of STS in dysfunctional ventricles remains unknown. Here, we assessed the effects of STS in the failing heart...

..The results concluded that homocysteine generated nitrotyrosine in the vicinity of endothelium, caused MMP activation and endothelium-myocyte uncoupling. The generation of nitrotyrosine was independent of iNOS...

..Hyperhomocysteinemia (HHcy) and hyperglycemia cause diabetic cardiomyopathy by inducing oxidative stress and attenuating peroxisome proliferator- activated receptor (PPAR) gamma. However, their synergistic contribution is not clear...

..The results show that arterial hypertension in HHcy mice is, in part, associated with arterial remodeling and E-M uncoupling in response to MMP activation...

..We conclude that HHCY activates mtMMP-9 and induces MPT, leading to myocyte mechanical dysfunction by agonizing NMDA-R1...

..This led to mitophagy, in part, by activating NMDA-R1. The findings of this study will lead to therapeutic ramifications for mitigating cardiovascular diseases by inhibiting the mitochondrial mitophagy and NMDA-R1 receptor...

..We showed that FA supplementation resulted in significant improvement of myocardial function after MI. The study eluted the importance of homocysteine (Hcy) metabolism and FA supplementation in cardiovascular disease...

..The levels of ADAM-12, apoptosis, and fibrosis were robust and integrin were decreased in AVF hearts. The treatment with H(2)S donor attenuated the fibrosis, apoptosis, and decrease in integrin...

..Results show that an increase in iNOS activity is a key contributor to HHcy-mediated collagen/elastin switch and resulting decline in aortic compliance...

..This review suggest that Hcy increases iNOS/NO, superoxide, metalloproteinase activity, and disrupts connexin-43, exacerbates endothelial-myocyte uncoupling and cardiac failure secondary to inducing NMDA-R1...

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..It points to the involvement of beta2-AR in diabetic cardiomyopathy. We conclude that degradation of beta2-AR and impairment of Hcy metabolism is implicated in diabetic cardiomyopathy...

..Interestingly, these effects were ameliorated by FA and suggested that FA supplementation may have therapeutic potential against genetically HHcy induced bone loss...

..We conclude that diabetes-induced intra-renal mitochondrial oxidative stress is reflected by an increase in mitochondrial membrane permeability and protein modifications by nitrotyrosine generation...

..Hcy induced higher protein nitrotyrosination and cytosolic NADPHoxidase subunit p22(phox) in cochlea. It is thus suggested that Hcy induced matrix imbalance, structural changes and oxidative stress in cochlea...

..The results suggested that Hcy caused cerebral interstitial remodeling in brain by distorting the extracellular matrix, thus increasing the blood brain permeability; treatment with muscimol mitigated BBB permeability...

..Results suggest that a PPARgamma agonist ameliorates preglomerular arteriole remodeling in diabetes by decreasing tissue levels of Hcy and MMP-2 activity and increasing NO...

..We conclude that conversion of Hcy to H(2)S by CBS, CSE, or 3MST triple gene therapy improves renovascular function in HHcy...

..However, in vitro DZA and CBS gene therapy successfully treated the HHcy-induced inflammatory reaction in the methionine metabolism pathway...

..However, in decompensatory hearts there was increase in MMP-9, TIMP-3, endostatin, angiostatin and vascular rarefaction...

..2 +/- 1.9, 9.7 +/- 0.2, 16.6 +/- 0.8 (P < 0.05 compared with WT), 13.1 +/- 2.1 dyn/cm(2). The results suggest that Hcy increased aortic wall stress by increasing nitrotyrosine and MMP-9 activity...

..In conclusion, the administration of H2S protected the cells from oxidative stress induced by hyperhomocysteinemia (HHcy), which suggested that NaHS/H2S may have therapeutic potential against Met-induced oxidative stress...

..Efficacy of B vitamin supplementation in patient populations with HHcy and CHD is also reviewed...

..The data suggest that Hcy increases EC layer permeability through inhibition of GABA(A) receptor and F-actin formation, in part, by transducing ERK and MMP-9 activation...

..Moreover, the therapeutic implications of NMDA and PPAR ligands are some promise to patient...

..The results suggested no detectable differential G(s) and G(i) expression. This suggested that Hcy did not act as an agonist in vitro to alter G protein content, but that Hcy produced some other in vivo effects to incur these results...

..To compensate, the heart increases its load which creates adverse cardiac remodeling in which the elastin/collagen ratio is reduced, causing cardiac stiffness and diastolic heart failure in hyperhomocysteinemia...

..The miRNA microarray assay revealed differential expression of 11 miRNAs and among them miR-188 show dramatic downregulation. These findings suggest that dicer and miRNAs especially miR-188 are involved in Hcy-induced cardiac remodeling...

..Treatment with FA abolished this effect in PAC mice. These results suggest that FA treatment improves MMP/TIMP balance and ameliorates mitochondrial dysfunction that results in protection of RV failure during pulmonary hypertension...

..The decreased levels of thioredoxin and peroxiredoxin and cardiac tissue inhibitor of metalloproteinase are in response to antagonizing PPARgamma...

..9 ± 0.1 in the Hcy-treated group. The tibia bone density was unchanged in Hcy-treated rats. These results suggest that Hcy causes a reduction in bone blood flow, which contributes to compromised bone biomechanical properties...

..Although it is known that oxidative stress activates MMP and CIMP inhibits MMP, it is unclear whether CIMP administration attenuates oxidative stress and MMP-mediated cardiac dilatation...

..This occurred, in part, by the inhibition of NF-kappabeta nuclear translocation, NF-kappabeta-DNA binding and activation of IKbetaalpha. The study unequivocally suggested the pivotal role of EETs in the modulation of Hcy/MMP-9 signal...

..Our data suggested that Hcy-mediated ROS production promotes endothelial cell death in part by disturbing MP, which results in subsequent release of cytochrome-c and activation of caspase-9 and 3, leading to cell death...

..These findings contribute to clarification of mechanisms of IBD development...

..The signal transduction mechanisms in Hcy-induced matrix metalloproteinase (MMP) activation in cardiac connexin remodeling are discussed...

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..In light of the present information, this review focuses on the mechanism of hyperhomocysteinemia-associated hypertension and highlights the novel modulatory role of H(2)S to ameliorate hypertension...

..The present study indicates that elevated un-degraded Fg may be a factor causing microvascular permeability that typically accompanies cardiovascular and cerebrovascular disorders...

..The mechanisms for the impairment of vascular function and therapeutic effects of FA may be related to the regulation of eNOS expression, NO availability and tissue homocysteine...

..Treatment with a broad-range MMP inhibitor (GM-6001; 1 microM) ameliorated Hcy-induced F-actin formation. These data suggest that Hcy increases microvascular permeability, in part, through MMP-9 activation...

..These results suggest that Hcy competes with CF and PGJ(2) for binding to PPAR-alpha and -gamma, respectively, indicating a role of PPAR in amelioration of Hcy-mediated EE dysfunction...

..The results suggest that in the absence of endothelial NO, and in an attempt to reduce LV load, MMP-2 is activated and CIMP is inactivated, by increasing nitrotyrosine...

..We conclude that inhibition of MMP9 ameliorates stem cell survival and their differentiation into cardiomyocytes in diabetes...

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..Together our results suggest that CS- and HHcy-induced oxidative stress synergistically contribute to small GTPase membrane translocation and focal adhesion protein redistribution leading to endothelial remodeling...

..There is selective inhibition of miR-376b and over-expression of miR-1, miR-26a, miR-30d, and miR-181c in MMP-9KO that are implicated in regulation of G-PCR and calcium handling...

..The aim of the present study was to examine the expression of GABA(A) receptor and its subunits in non-neural tissue...

..Our results provide evidence that Hcy triggers the PTX-sensitive ERK1/2 signaling pathway, which is involved in the regulation of MMP-9 in MVECs...

..We concluded that the congenic transfer of TIMP ameliorated LV hypertrophy and cardiac dysfunction...

..These results suggest that E-M uncoupling in the myocardium, in part, is due to increased MMP activities secondary to suppressing PPARgamma activity in high-fat, calorie-induced Type 2 diabetes mellitus...

..Our results suggest that elevated blood level of Fg could have a significant role in cerebrovascular dysfunction and remodeling...

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..This early mechanism for the initiation of LV remodeling appears to have a role in end-stage human heart failure...

..In vitro, treatment of CIMP abrogated the DMP activity. The treatment with CIMP may prevent degradation of integrin and connexin and ameliorate heart failure...

..We conclude that H₂S plays a regulatory role in Hcy-induced mesangial inflammation and that ERK1/2 and JNK1/2 are two signaling pathways involved this process...

..We have shown that purified TIMP-4 blocked the increase of beta-1 integrin shedding in Hcy-treated cells. Interestingly, our results suggest that TIMP-1 and TIMP-4 function antagonistically in Hcy-induced signaling pathways...

..Identification of major players involved in the control of oxidative and proteolytic stresses that ameliorate matrix deposition by integrin shading will help to develop strategies to prevent congestive heart failure...

..Therefore, we hypothesized that Hcy activates AT1 receptor that potentiates STAT3 via ERK-1/2 phosphorylation. STAT3 modulates target MMP-9 and collagen, resulting in vascular remodeling...

..However, CIMP inhibits only homocysteine-mediated contraction. The results suggest that homocysteine may enhance vascular constrictive remodeling by inactivating PPAR-alpha and -gamma in ECs and PPAR-gamma in SMCs...

..These results may suggest a differential role of L- and D-isomers in vascular versus cardiac remodeling...

..These results suggest a synergistic action between insulin and C-peptide that facilitates increase NO availability and may suggest new clinical treatment modalities for type-1 diabetes mellitus...

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..The results suggest that an increase in the oxidative stress and generation of nitrotyrosine are, in part, responsible for the activation of metalloproteinase and decreased endocardial endothelial function in chronic LV volume overload...

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..The accumulation of cardiac collagen was associated with induction of Hcy and TGF-beta1 and with suppression of decorin...

..The cell-extracellular matrix connections are important in maintaining and synchronizing muscle function. However, a complete extracellular matrix-cell disconnect leads to a decrease in muscle cell strength, apoptosis, and hypertrophy...

..This scenario is possible, if the activities of both the enzymes (CBS and CGL) are increased in tissues by gene therapy...

..The results of this study indicated amelioration of Hcy-induced MVEC collagen gel constriction by induction of nitric oxide through GABA-A and -B receptors...

..In this review we discussed stem cells as a potential future therapeutic target for the treatment of diabetes and associated diseases...

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..Appropriately, we need to examine the mechanisms that result in the development and transition from diastolic and systolic dysfunction to the clinical syndrome of overt CHF with its inherent increase in morbidity and mortality...

..Taken together, these findings determine the novel role of mitochondrial translocation of calpain-1 in MMP-9 activation during HHcy, in part, by increasing mitochondrial oxidative stress...

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..This review discusses the relationship between ROS, RNS, P-selectin, and platelet-arteriolar wall interactions and proposes a hypothesis for their role in microvascular responses during pulmonary IR...

..The presence of islet amyloid has also been described in association with type 2 diabetes mellitus for a century...

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..The treatment with ARB mitigates this disruption in cardiac synchrony...

..Thus, rapid pacing-induced atrial failure is associated with differential changes in MMP activity, an unchanged number of calcium pumps, and compensatory changes in the level of phospholamban...

..In conclusion, our results suggest that AS leads to increased oxidative stress, expression/activity of MMP-2/9 and a decrease in antioxidant expression producing collagen degradation and heart failure...

..However, the mechanism of matrix accumulation is unclear. Spontaneously hypertensive rats (SHR) develop hypertension at between 2 and 6 weeks of age...

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..The non-antibiotic property of tetracycline may be of potential value in the prevention of ventricular dilatation in idiopathic dilated cardiomyopathy...

..The pain, foot ulceration, limb loss, organ dysfunction, and the associated morbidity and financial burden all contribute to the need for a better understanding of DPN and the role of redox stress and global risk reduction...

..CIMP treatment normalized PAR-1 expression and ameliorated endothelial-myocyte uncoupling by decreasing oxidant-mediated proteolytic stress in CHF...

..The endothelium seems to be at the very center of these disease processes, acting as the first line of defense against these multiple metabolic toxicities and the first to encounter their damaging effects to the arterial vessel wall...

..The results suggest that impaired cardiac function in volume overload is associated with EE apoptosis, cardiac remodeling, and endothelium-myocytes uncoupling in response to MMP-9 activation...

..Future studies need to explore the pathomechanisms of HHCY in CHF. Moreover, larger intervention trials are needed to clarify whether modification of plasma HCY by B-vitamin supplementation improves the clinical outcome in CHF patients...