Role of myeloperoxidase in abdominal aortic aneurysm formation: mitigation by taurine.

Oxidative stress plays a fundamental role in abdominal aortic aneurysm (AAA) formation. Activated polymorphonuclear leukocytes (or neutrophils) are associated with AAA and express myeloperoxidase (MPO), which promotes inflammation, matrix degradation, and other pathological features of AAA, including enhanced oxidative stress through generation of reactive oxygen species. Both plasma and aortic MPO levels are elevated in patients with AAA, but the role of MPO in AAA pathogenesis has, heretofore, never been investigated. Here, we show that MPO gene deletion attenuates AAA formation in two animal models: ANG II infusion in apolipoprotein E-deficient mice and elastase perfusion in C57BL/6 mice. Oral administration of taurine [1% or 4% (wt/vol) in drinking water], an amino acid known to react rapidly with MPO-generated oxidants like hypochlorous acid, also prevented AAA formation in the ANG II and elastase models as well as the CaCl2 application model of AAA formation while reducing aortic peroxidase activity and aortic protein-bound dityrosine levels, an oxidative cross link formed by MPO. Both MPO gene deletion and taurine supplementation blunted aortic macrophage accumulation, elastin fragmentation, and matrix metalloproteinase activation, key features of AAA pathogenesis. Moreover, MPO gene deletion and taurine administration significantly attenuated the induction of serum amyloid A, which promotes ANG II-induced AAAs. These data implicate MPO in AAA pathogenesis and suggest that studies exploring whether taurine can serve as a potential therapeutic for the prevention or treatment of AAA in patients merit consideration.NEW & NOTEWORTHY Neutrophils are abundant in abdominal aortic aneurysm (AAA), and myeloperoxidase (MPO), prominently expressed in neutrophils, is associated with AAA in humans. This study demonstrates that MPO gene deletion or supplementation with the natural product taurine, which can scavenge MPO-generated oxidants, can prevent AAA formation, suggesting an attractive potential therapeutic strategy for AAA.

Draft Genome Sequence of an Extreme Haloarchaeon 3A1-DGR Isolated from a Saltern Crystallizer of the Little Rann of Kutch, India.

Haloarchaea are predominant in the salt crystallizers of the Rann of Kutch when the concentration of salts approaches saturation levels. The obligate and extreme halophilic archaeon 3A1-DGR, isolated from a salt crystallizer pond of the Little Rann of Kutch, India, needs minimum of 10 % NaCl in the growth medium. To understand the mechanism(s) of osmotolerance and adaptation at extreme osmolarity, and to mine relevant gene(s), the genome of this haloarchaeon, 3A1-DGR, was sequenced. We report here, the 2.88 Mb draft genome sequence of the haloarchaeon 3A1-DGR, with G+C content of 68 % and the possible involvement of 43 genes in stress tolerance. Further studies of the genome of this haloarchaeon would be required to identify gene(s) that might be responsible for imparting extreme osmotolerance.

Alleviation of Salinity Stress in Peanut by Application of Endophytic Bacteria.

The development of salinity affects 7% of the world's land surface, acting as a major constraint to crop productivity. This study attempted to use the co-evolving endophytes of peanut to alleviate salinity stress and enhance the yield of peanut. Diverse and different tissue colonizing endophytes were isolated from peanut and screened in vitro by seed germination bioassay imposing gradients of salinity, with two cultivars TG37A (susceptible) and GG2 (moderately resistant), in potted conditions using saline irrigation water. Finally, nine endophytes capable of producing IAA and ACC-deaminase, promoting root growth and yield in potted conditions were selected for further evaluation in field conditions. They were evaluated with saline water (1.5-2.0 dS/m) in saline soil with susceptible cultivar TG37A. Simultaneously, three endophytes (Bacillus firmus J22N; Bacillus tequilensis SEN15N; and Bacillus sp. REN51N) were evaluated with two cultivars, GG2 and TG37A, during rainy and post-rainy seasons with elevated salinity. The application of endophytes like Bacillus firmus J22N and Bacillus sp. REN51N enhanced the pod and haulm yield of peanuts by 14-19% across cultivars, salinity, and seasons. In addition, there was significant modulation in parameters like relative water content; production of enzymes like superoxide dismutase (SOD), glutathione reductase (GR), catalase (CAT), ascorbate peroxidase (APX), lipid peroxidase (POD), and H2O2 content in leaf; and uptake of potassium. The activities of the enzymes involved in scavenging reactive oxygen species (ROS) increased with salinity, and further increased with endophytes like Bacillus firmus J22N, Bacillus tequilensis SEN15N, and Bacillus sp. REN51N. There was an enhanced accumulation of proline, reduced level of phenol and H2O2, and enhanced uptake of potassium with the inoculation of endophytes. This improved scavenging capacity of plants by endophytic modulation of ROS scavengers, uptake of K, production of ACC deaminase and IAA, root and biomass growth, modulation in relative water content, and enhanced accumulation of osmoprotectant might be the reasons of alleviation of salinity stress. Endophytes could have alleviated salinity stress in peanuts, indicating the mechanisms and potential of peanuts at the field level. These endophytes could be applied to bring agricultural sustainability to salinity-affected areas in the future. Furthermore, few genera viz. Kocuria, Brevundimonas, Agrococcus, Dietzia, and Kytococcus were observed in peanut tissue for the first time.

Deletion of p47phox attenuates angiotensin II-induced abdominal aortic aneurysm formation in apolipoprotein E-deficient mice.

BACKGROUND: Angiotensin II (Ang II) contributes to vascular pathology in part by stimulating NADPH oxidase activity, leading to increased formation of superoxide (O2-). We reported that O2- levels, NADPH oxidase activity, and expression of the p47phox subunit of NADPH oxidase are increased in human abdominal aortic aneurysms (AAAs). Here, we tested the hypothesis that deletion of p47phox will attenuate oxidative stress and AAA formation in Ang II-infused apoE-/- mice. METHODS AND RESULTS: Male apoE-/- and apoE-/-p47phox-/- mice received saline or Ang II (1000 ng x kg(-1) x min(-1)) infusion for 28 days, after which abdominal aortic weight and maximal diameter were determined. Aortic tissues and blood were examined for parameters of aneurysmal disease and oxidative stress. Ang II infusion induced AAAs in 90% of apoE-/- versus 16% of apo-/-p47phox-/- mice (P < 0.05). Abdominal aortic weight (14.1 +/- 3.2 versus 35.6 +/- 9.0 mg), maximal aortic diameter (1.5 +/- 0.2 versus 2.4 +/- 0.4 mm), aortic NADPH oxidase activity, and parameters of oxidative stress were reduced in apoE-/-p47phox-/- mice compared with apoE-/- mice (P < 0.05). In addition, aortic macrophage infiltration and matrix metalloproteinase-2 activity were reduced in apoE-/-p47phox-/- mice compared with apoE-/- mice. Deletion of p47phox attenuated the pressor response to Ang II; however, coinfusion of phenylephrine with Ang II, which restored the Ang II pressor response, did not alter the protective effects of p47phox deletion on AAA formation. CONCLUSIONS: Deletion of p47phox attenuates Ang II-induced AAA formation in apoE-/- mice, suggesting that NADPH oxidase plays a critical role in AAA formation in this model.

Vitamin E inhibits abdominal aortic aneurysm formation in angiotensin II-infused apolipoprotein E-deficient mice.

BACKGROUND: Abdominal aortic aneurysms (AAAs) in humans are associated with locally increased oxidative stress and activity of NADPH oxidase. We investigated the hypothesis that vitamin E, an antioxidant with documented efficacy in mice, can attenuate AAA formation during angiotensin II (Ang II) infusion in apolipoprotein E-deficient mice. METHODS AND RESULTS: Six-month-old male apolipoprotein E-deficient mice were infused with Ang II at 1000 ng/kg per minute for 4 weeks via osmotic minipumps while consuming either a regular diet or a diet enriched with vitamin E (2 IU/g of diet). After 4 weeks, abdominal aortic weight and maximal diameter were determined, and aortic tissues were sectioned and examined using biochemical and histological techniques. Vitamin E attenuated formation of AAA, decreasing maximal aortic diameter by 24% and abdominal aortic weight by 34% (P<0.05, respectively). Importantly, animals treated with vitamin E showed a 44% reduction in the combined end point of fatal+nonfatal aortic rupture (P<0.05). Vitamin E also decreased aortic 8-isoprostane content (a marker of oxidative stress) and reduced both aortic macrophage infiltration and osteopontin expression (P<0.05, respectively). Vitamin E treatment had no significant effect on the extent of aortic root atherosclerosis, activation of matrix metalloproteinases 2 or 9, serum lipid profile, or systolic blood pressure. CONCLUSIONS: Vitamin E ameliorates AAAs and reduces the combined end point of fatal+nonfatal aortic rupture in this animal model. These findings are consistent with the concept that oxidative stress plays a pivotal role in Ang II-driven AAA formation in hyperlipidemic mice.

Draft Genome Sequence of a Moderately Halophilic Bacillus megaterium Strain, MSP20.1, Isolated from a Saltern of the Little Rann of Kutch, India.

The 4.37-Mbp draft genome of a moderately halophilic Bacillus megaterium strain, MSP20.1, isolated from a saltern of the Little Rann of Kutch, India, is reported here. To understand the mechanism(s) of moderate halophilism and to isolate the gene(s) involved in osmotolerance and adaptation, the genome of MSP20.1 was sequenced.

Insight into the First Draft Genome Sequence of the Genus Sediminibacillus, Sediminibacillus halophilus Strain NSP9.3.

We report the 3.98-Mbp first draft genome sequence of Sediminibacillus halophilus strain NSP9.3, a moderate halophile isolated from a seasonal salt marsh of the Great Rann of Kutch, India. Exploring the genome of this organism will facilitate the understanding of the mechanism(s) of osmotolerance and survival in differential osmolarity.

Draft Genome Sequence of Bacillus sp. Strain SB47, an Obligate Extreme Halophile Isolated from a Salt Pan of the Little Rann of Kutch, India.

Here, we report the 4.46-Mbp draft genome sequence of Bacillus sp. strain SB47, an extreme halophile isolated from a salt pan of the Little Rann of Kutch, India. Exploring the genome of this organism will facilitate the understanding and isolation of the gene(s) involved in its extreme osmotolerance.

Draft Genome Sequence of Bacillus sp. Strain NSP9.1, a Moderately Halophilic Bacterium Isolated from the Salt Marsh of the Great Rann of Kutch, India.

We report the 4.52-Mbp draft genome sequence of Bacillus sp. strain NSP9.1, a moderately halophilic bacterium isolated from the salt marsh of the Great Rann of Kutch, India. Analysis of the genome of this organism will lead to a better understanding of the genes and metabolic pathways involved in imparting osmotolerance.

Draft Genome Sequence of the Extremely Halophilic Bacillus sp. Strain SB49, Isolated from a Salt Crystallizer Pond of the Little Rann of Kutch, India.

Here we report the draft whole-genome sequence (3.72 Mbp) of Bacillus sp. strain SB49, an extremely halophilic bacterium isolated from a salt crystallizer pond of the Little Rann of Kutch in India. Unraveling the genome of this organism will facilitate understanding and isolation of the genes involved in imparting extreme osmotolerance.

Draft Genome Sequence of the Obligate Halophilic Bacillus sp. Strain NSP22.2, Isolated from a Seasonal Salt Marsh of the Great Rann of Kutch, India.

Here, we report the 4.0-Mbp draft genome of an obligate halophile, Bacillus sp. strain NSP22.2, isolated from a seasonal salt marsh of the Great Rann of Kutch, India. To understand the mechanism(s) of obligate halophilism and to isolate the relevant gene(s), the genome of Bacillus sp. NSP22.2 was sequenced.

Draft Genome Sequence of Bacillus sp. Strain NSP2.1, a Nonhalophilic Bacterium Isolated from the Salt Marsh of the Great Rann of Kutch, India.

The 5.52-Mbp draft genome sequence of Bacillus sp. strain NSP2.1, a nonhalophilic bacterium isolated from the salt marsh of the Great Rann of Kutch, India, is reported here. An analysis of the genome of this organism will facilitate the understanding of its survival in the salt marsh.

Draft Genome Sequence of Salinibacillus aidingensis Strain MSP4, an Obligate Halophilic Bacterium Isolated from a Salt Crystallizer of the Rann of Kutch, India.

We report the 7.42-Mbp draft whole genome sequence of Salinibacillus aidingensis strain MSP4, an obligate halophilic bacterium, isolated from a salt crystallizer of the Rann of Kutch in India. Analysis of the genome of this organism will lead to a better understanding of the genes and metabolic pathways involved in imparting osmotolerance.

Draft Genome Sequence of an Obligate and Moderately Halophilic Bacterium, Thalassobacillus devorans Strain MSP14, the First Draft Genome of the Genus Thalassobacillus.

We report the 3.93-Mbp first draft genome sequence of a species of the genus Thalassobacillus, Thalassobacillus devorans strain MSP14, a moderate but obligate halophile, isolated from a salt crystallizer of the Little Rann of Kutch, India. Exploring the genome of this organism will facilitate understanding the mechanism(s) of its obligate halophilism.

CD14 directs adventitial macrophage precursor recruitment: role in early abdominal aortic aneurysm formation.

BACKGROUND: Recruitment of macrophage precursors to the adventitia plays a key role in the pathogenesis of abdominal aortic aneurysms (AAAs), but molecular mechanisms remain undefined. The innate immune signaling molecule CD14 was reported to be upregulated in adventitial macrophages in a murine model of AAA and in monocytes cocultured with aortic adventitial fibroblasts (AoAf) in vitro, concurrent with increased interleukin-6 (IL-6) expression. We hypothesized that CD14 plays a crucial role in adventitial macrophage precursor recruitment early during AAA formation. METHODS AND RESULTS: CD14(-/-) mice were resistant to AAA formation induced by 2 different AAA induction models: aortic elastase infusion and systemic angiotensin II (AngII) infusion. CD14 gene deletion led to reduced aortic macrophage infiltration and diminished elastin degradation. Adventitial monocyte binding to AngII-infused aorta in vitro was dependent on CD14, and incubation of human acute monocytic leukemia cell line-1 (THP-1) monocytes with IL-6 or conditioned medium from perivascular adipose tissue (PVAT) upregulated CD14 expression. Conditioned medium from AoAf and PVAT induced CD14-dependent monocyte chemotaxis, which was potentiated by IL-6. CD14 expression in aorta and plasma CD14 levels were increased in AAA patients compared with controls. CONCLUSIONS: These findings link CD14 innate immune signaling via a novel IL-6 amplification loop to adventitial macrophage precursor recruitment in the pathogenesis of AAA.

Role of thrombectomy in acute myocardial infarction.

Acute ST elevation myocardial infarction results from atherosclerotic plaque rupture with subsequent thrombus formation, leading to complete or near complete occlusion of an epicardial coronary artery. Minimization of the mechanical obstruction from this thrombus remains the main goal of therapy in ST elevation myocardial infarction. Primary percutaneous coronary intervention for an ST elevation myocardial infarction appears to be the preferred mode of revascularization over thrombolytic therapy if the door-to-balloon time target of 90 min is achievable. The idea of reducing the thrombus burden with the use of devices as an adjunct to percutaneous coronary intervention is an attractive one. Several thrombectomy devices have been studied in randomized clinical trials, but no definitive conclusions have emerged, owing to conflicting results and variable clinical end points. This article intends to shed further light on the potential role of thrombectomy in the treatment of acute myocardial infarction.

Zinc dyshomeostasis in rats with aldosteronism. Response to spironolactone.

Zinc is a structural constituent of many proteins, including Cu/Zn superoxide dismutase (SOD), an endogenous antioxidant enzyme. Hypozincemia has been found in patients hospitalized with congestive heart failure, where neurohormonal activation, including the renin-angiotensin-aldosterone system (RAAS), is expected and oxidative stress is present. This study was undertaken to elucidate potential pathophysiological mechanisms involved in Zn dyshomeostasis in aldosteronism. In rats receiving aldosterone/salt treatment (ALDOST) alone for 1 and 4 wk or in combination with spironolactone (Spiro), an ALDO receptor antagonist, we monitored 24-h urinary and fecal Zn excretion and tissue Zn levels in heart, liver, and skeletal muscle, together with tissue metallothionein (MT)-I, a Zn(2+)-binding protein, and Cu/Zn-SOD activities in plasma and tissues. When compared with unoperated, untreated, age-/sex-matched controls, urinary and, in particular, fecal Zn losses were markedly increased (P < 0.05) at days 7 and 28 of ALDOST, leading to hypozincemia and a fall (P < 0.05) in plasma Cu/Zn-SOD activity. Microscopic scars and perivascular fibrosis of intramural coronary arteries first appeared in the right and left ventricles at week 4 of ALDOST and were accompanied by increased (P < 0.05) tissue Zn, MT-I, and Cu/Zn-SOD activity, which were not found in uninjured liver or skeletal muscle. Spiro cotreatment prevented cardiac injury and Zn redistribution to the heart. Thus increased urinary and fecal Zn losses, together with their preferential translocation to sites of cardiac injury, where MT-I overexpression and increased Cu/Zn-SOD activity appeared, contribute to Zn dyshomeostasis in rats with aldosteronism, which were each prevented by Spiro. These findings may shed light on Zn dyshomeostasis found in patients with decompensated heart failure.