Lysozyme, a mediator of sepsis that produces vasodilation by hydrogen peroxide signaling in an arterial preparation

Mink, Steven N.; Kasian, Krika; Martinez, Luis; Jacobs, Hans; Bose, Ratna; Cheng, Zhao-Qin; Light, R. Bruce

doi:10.1152/ajpheart.01072.2007

Cited by 12 publications

(53 citation statements)

References 50 publications

(94 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Burke and Wolin (5, 6) described a unique pathway by which H 2 O 2 caused vasodilation in a preconstricted pulmonary artery preparation. We showed that a similar pathway participated in the vasodilatory response of Lzm-S in recent experiments (28). In a phenylephrine-constricted carotid artery preparation, we demonstrated that the generation of H 2 O 2 by Lzm-S led to the formation of compound I, a species of catalase that is the product of the metabolism of H 2 O 2 .…”

mentioning

confidence: 51%

“…Compound I then caused activation of smooth muscle soluble guanylate cyclase (sGC), which subsequently resulted in an increase in guanosine 3Ј,5Ј-cyclic monophosphate (cGMP) and thereby produced vasorelaxation. We further demonstrated that ethanol, an inhibitor of compound I, the peroxidizing agent Aspergillus niger catalase, a competitor of endogenous catalase, and inhibitors of sGCcGMP-protein kinase G (PKG) pathway all prevented the vasodilator effect of Lzm-S (28). Moreover, we showed that the vasodilatory response of Lzm-S was not related to the presence of heavy metals [as performed by Buettner (4)] or to changes in pH or calcium in the organ bath and that denatured Lzm-S did not cause vasodilation in our carotid artery preparation (28).…”

mentioning

confidence: 93%

“…When we determined the pathway of vasodilation in an in vitro preparation, we were surprised to find that the initiating signaling event was the generation of H 2 O 2 by Lzm-S, although we did not define the mechanism by which this generation occurred (28). H 2 O 2 has been found to be an important mediator that contributes to cardiovascular signaling under many conditions.…”

mentioning

confidence: 96%

“…There are distinct differences between the pathways that are involved in Lzm-S-induced vasodilation and Lzm-Sinduced myocardial depression. Arterial vasodilation is both independent of the intact endothelium and unrelated to nitric oxide (NO) signaling, since removal of the endothelium and administration of the nitric oxide synthase (NOS) inhibitor N G -monomethyl-L-arginine (L-NMMA), respectively, did not inhibit the effect of Lzm-S in the organ bath preparation (28). On the other hand, to cause steady myocardial depression, Lzm-S needs to bind to a glycoprotein moiety on the endocardial endothelium, particularly to the mannose-␤(1-4) N-acetylglucosamine (GlcNAc)-(␤1-4)GlcNAc moiety of high mannose/hybrid and tri-antennary glycan subtypes (17).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Lysozyme, a mediator of sepsis that intrinsically generates hydrogen peroxide to cause cardiovascular dysfunction

Mink

Jacobs²,

Cheng³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

In septic shock, cardiovascular collapse is caused by the release of inflammatory mediators. We previously found that lysozyme (Lzm-S), released from leukocytes, contributed to the myocardial depression and arterial vasodilation that develop in canine models of septic shock. To cause vasodilation, Lzm-S generates hydrogen peroxide (H(2)O(2)) that activates the smooth muscle soluble guanylate cyclase (sGC) pathway, although the mechanism of H(2)O(2) generation is not known. To cause myocardial depression, Lzm-S binds to the endocardial endothelium, resulting in the formation of nitric oxide (NO) and subsequent activation of myocardial sGC, although the initial signaling event is not clear. In this study, we examined whether the myocardial depression produced by Lzm-S was also caused by the generation of H(2)O(2) and whether Lzm-S could intrinsically generate H(2)O(2) as has been described for other protein types. In a canine ventricular trabecular preparation, we found that the peroxidizing agent Aspergillus niger catalase, that would breakdown H(2)O(2), prevented Lzm-S- induced decrease in contraction. We also found that compound I, a species of catalase formed during H(2)O(2) metabolism, could contribute to the NO generation caused by Lzm-S. In tissue-free experiments, we used a fluorometric assay (Ultra Amplex red H(2)O(2) assay) and electrochemical sensor techniques, respectively, to measure H(2)O(2) generation. We found that Lzm-S could generate H(2)O(2) and, furthermore, that this generation could be attenuated by the singlet oxygen quencher sodium azide. This study shows that Lzm-S, a mediator of sepsis, is able to intrinsically generate H(2)O(2). Moreover, this generation may activate H(2)O(2)-dependent pathways leading to cardiovascular collapse in septic shock.

show abstract

mentioning

confidence: 51%

mentioning

confidence: 93%

mentioning

confidence: 96%

mentioning

confidence: 99%

See 2 more Smart Citations

Lysozyme, a mediator of sepsis that intrinsically generates hydrogen peroxide to cause cardiovascular dysfunction

Mink

Jacobs²,

Cheng³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Also, ferritin light chain 1 (Ftl1) was upregulated in both muscle and aortae, possibly reflecting the presence of oxidized low-density lipoproteins in diabetic endothelium (16). One other transcript dysregulated in both aortic and skeletal muscle endothelium, lysozyme 1 (Lyz1), is involved in the modulation of AGEs (43) and is a vasodilator (27).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional analysis of the endothelial response to diabetes reveals a role for galectin-3

Darrow

Shohet

Maresh

2011

Physiological Genomics

View full text Add to dashboard Cite

Darrow AL, Shohet RV, Maresh JG. Transcriptional analysis of the endothelial response to diabetes reveals a role for galectin-3. Physiol Genomics 43: 1144 -1152, 2011. First published July 26, 2011 doi:10.1152/physiolgenomics.00035.2011.-To characterize the endothelial dysfunction associated with Type II diabetes, we surveyed transcriptional responses in the vascular endothelia of mice receiving a diabetogenic, high-fat diet. Tie2-GFP mice were fed a diet containing 60% fat calories (HFD); controls were littermates fed normal chow. Following 4, 6, and 8 wk, aortic and leg muscle tissues were enzymatically dispersed, and endothelial cells were obtained by fluorescence-activated cell sorting. Relative mRNA abundance in HFD vs. control endothelia was measured with long-oligo microarrays; highly dysregulated genes were confirmed by real-time PCR and protein quantification. HFD mice were hyperglycemic by 2 wk and displayed vascular insulin resistance and decreased glucose tolerance by 5 and 6 wk, respectively. Endothelial transcripts upregulated by HFD included galectin-3 (Lgals3), 5-lipoxygenase-activating protein, and chemokine ligands 8 and 9. Increased LGALS3 protein was detected in muscle endothelium by immunohistology accompanied by elevated LGALS3 in the serum of HFD mice. Our comprehensive analysis of the endothelial transcriptional response in a model of Type II diabetes reveals novel regulation of transcripts with roles in inflammation, insulin sensitivity, oxidative stress, and atherosclerosis. Increased endothelial expression and elevated humoral levels of LGALS3 supports a role for this molecule in the vascular response to diabetes, and its potential as a direct biomarker for the inflammatory state in diabetes. gene expression; microarray; vascular biology; endothelial dysfunction; metabolic syndrome TYPE II DIABETES IS ASSOCIATED with increased atherosclerosis, retinopathy, skin ulceration, and other vascular-related diseases, all of which may involve damaged or dysfunctional endothelium. A major consequence of diabetes is endothelial exposure to elevated glucose and fatty acids, leading to endothelial nitric oxide synthase uncoupling and subsequent generation of reactive oxygen and nitrogen species (46) as well as the formation of advanced glycation end-products (AGEs) (45). Furthermore, hyperinsulinemia and other hormonal changes can alter endothelial signaling pathways (34). These changes may promote inflammation, impair vasoregulation, disrupt hemostasis, and inhibit reverse cholesterol transport (2, 32). By examining the transcriptional changes that occur in both the micro-and macrovascular endothelium of mice exposed to a dietary model of Type II diabetes, we expect to gain further insight into the underlying mechanisms of the endothelial dysfunction characteristic of diabetes and the metabolic syndrome.Transcriptional analysis has been used to examine the responses of cultured endothelium exposed to high glucose and insulin (9, 44). However, an in vitro analysis may only partially reflect the co...

show abstract

Cardiovascular Responses During Sepsis

Pecchiari

Pontikis

Alevrakis

et al. 2021

Comprehensive Physiology

View full text Add to dashboard Cite

Sepsis is the life-threatening organ dysfunction arising from a dysregulated host response to infection.Although the specific mechanisms leading to organ dysfunction are still debated, impaired tissue oxygenation appears to play a major role, and concomitant hemodynamic alterations are invariably present. The hemodynamic phenotype of affected individuals is highly variable for reasons that have been partially elucidated. Indeed, each patient's circulatory condition is shaped by the complex interplay between the medical history, the volemic status, the interval from disease onset, the pathogen, the site of infection and the attempted resuscitation. Moreover, the same hemodynamic pattern can be generated by different combinations of various pathophysiological processes, so the presence of a given hemodynamic pattern cannot be directly related to a unique cluster of alterations. Research based on endotoxin administration to healthy volunteers and animal models compensate, to an extent, for the scarcity of clinical studies on the evolution of sepsis hemodynamics. Their results, however, cannot be directly extrapolated to the clinical setting, due to fundamental differences between the septic patient, the healthy volunteer and the experimental model. Numerous microcirculatory derangements might exist in the septic host, even in the presence of a preserved macrocirculation. This dissociation between the macro-and the micro-circulation might account for the limited success of therapeutic interventions targeting typical hemodynamic parameters, such as arterial and cardiac filling pressures, and cardiac output. Finally, physiological studies point to an early contribution of cardiac dysfunction to the septic phenotype, however our defective diagnostic tools preclude its clinical recognition.) to anesthetized, vagotomized and mechanically ventilated Sprague-Dawley rats on the operating point of the baroreflex using a baroreflex diagram (SNA: sympathetic nervous activity; CSP: carotid sinus pressure; AP: arterial pressure). As time passes after lipopolysaccharide injection, the neural arc 9 progressively shifts rightwards, and the peripheral arc downwards, so the operating point moves from a (baseline) to b at 1 hour and to c at 2 hours, showing a progressive increase of SNA with little change of AP. From (523), with permission under the terms of the Creative Commons Attribution License. significantly (from 1.7±0.5 to 1.4±0.2 mmHg ml -1 min) (313). In the same preparation N w -nitro-L-methyl ester (L-NAME) increases SVR more than R VR both in the presence (+294 and +129%, respectively) and in the absence (+196 and +107%, respectively) of fluid-loading. In another study from the same group, L-NAME elicited similar effects (117). Overall, these experimental studies warn against the assumption that changes of SVR are always paralleled by similar changes of R VR .

show abstract

Lysozyme, a mediator of sepsis that produces vasodilation by hydrogen peroxide signaling in an arterial preparation

Cited by 12 publications

References 50 publications

Lysozyme, a mediator of sepsis that intrinsically generates hydrogen peroxide to cause cardiovascular dysfunction

Lysozyme, a mediator of sepsis that intrinsically generates hydrogen peroxide to cause cardiovascular dysfunction

Transcriptional analysis of the endothelial response to diabetes reveals a role for galectin-3

Cardiovascular Responses During Sepsis

Contact Info

Product

Resources

About