Cardiorenal Syndrome Type 5 in Sepsis: Role of Endotoxin in Cell Death Pathways and Inflammation

Virzì, Grazia Maria; Clementi, Anna; Brocca, Alessandra; Cal, Massimo de; Marcante, Stefano; Ronco, Claudio

doi:10.1159/000452602

Cited by 23 publications

(24 citation statements)

References 27 publications

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“…The increased expressions of PKC-α and PKC-β 2 mRNA are the primary cause of myocardial injury in DM [41, 42], however, the underlying downstream signal transduction pathway of PKC is still not completely understood. In addition, hyperglycemia can induce the formation of oxygen free radicals, promote the deposition of extracellular matrix, and decrease the diastolic function of the heart [43-46]. Mounting evidence has demonstrated that oxidative stress is involved in increased lipid peroxidation, aggravated myocardial reactivity and overexpression of chemoattractant in the myocardium [35, 36].…”

Section: Discussionmentioning

confidence: 99%

Chelerythrine Attenuates Renal Ischemia/ Reperfusion-induced Myocardial Injury by Activating CSE/H2S via PKC/NF-κB Pathway in Diabetic Rats

Xu²,

Zheng³

et al. 2017

Kidney Blood Press Res

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Background/Aims: Chelerythrine (CHE), a benzophenanthridine alkaloid, is a potent, selective, and cell-permeable protein kinase C (PKC) inhibitor. The purpose of the present study was to evaluate the effect of CHE on myocardial recovery after renal ischemia/reperfusion (I/R)-induced myocardial injury (RI/RMI) in a streptozocin (STZ)-induced diabetic rat model. Methods: Diabetes mellitus (DM) rats preconditioned with CHE and D, L-propargylglycine (PAG) were subjected to renal I/R. The extent of cardiac morphologic lesions and the biochemical markers of cardiorenal function and oxidative stress were detected utilizing hematoxylin-eosin staining, commercial kits, and enzyme-linked immunoassay, respectively. The expressions of cystathionine-γ-lyase (CSE), PKC-α, PKC-β₂, and nuclear factor-kappa B (NF-κB) in the rat myocardial tissue were measured utilizing western blotting. Results: Renal I/R treatment resulted in myocardial injury. CHE-preconditioning promoted the recovery from myocardial damage by ameliorating the biochemical parameters of myocardial injury, reducing oxidative stress, increasing the H₂S level, up-regulating the expression of CSE, and down-regulating the expressions of PKC-α, PKC-β₂, and NF-κB. Conclusion: These findings suggest that CHE-pretreatment may exert a protective effect on the myocardium against RI/RMI by activating endogenous CSE/H₂S via PKC/NF-κB pathway in STZ-induced diabetic rats. Further studies are needed defining underlying mechanisms.

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Section: Discussionmentioning

confidence: 99%

Chelerythrine Attenuates Renal Ischemia/ Reperfusion-induced Myocardial Injury by Activating CSE/H2S via PKC/NF-κB Pathway in Diabetic Rats

Xu²,

Zheng³

et al. 2017

Kidney Blood Press Res

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“…These conditions may affect each organ through common mechanisms (e.g., endotoxin) but also through disease-associated or pathogen-associated molecular patterns [51,52]. Specialists in the field of cardiology and nephrology may fruitfully collaborate to identify simultaneous cardiac and renal dysfunction in the setting of multiorgan system failure.…”

Section: Crs Typementioning

confidence: 99%

“…Finally, pathobiological mechanisms involving innate immunity, inflammation, and neurohormonal response have also been highlighted in the bidirectional nature of heart-kidney cross talk [19,20]. For example, it is well recognized that in the setting of critical illness, even in the absence of hypotension or marked electrolyte disturbances, both the heart and the kidney can manifest evidence of damage with elevations of cardiac troponin and novel markers of AKI [21]. For each mechanism and its resultant clinical syndrome, specific knowledge and skills are required to avoid harmful interventions and to provide the optimal supportive therapy to enable recovery.…”

Section: Introductionmentioning

confidence: 99%

A Call to Action to Develop Integrated Curricula in Cardiorenal Medicine

Ronco

McCullough

2017

Blood Purif

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With the adoption of the new definition and classification of cardiorenal syndrome (CRS) and its relevant subtypes, much attention has been placed on elucidating the mechanisms of heart and kidney interactions. Of great interest are the pathophysiological pathways by which acute heart failure may result in acute kidney injury (AKI; type 1), chronic heart failure accelerating the progression of chronic kidney disease (CKD; type 2), AKI provoking cardiac events (type 3), and CKD increasing the risk and severity of cardiovascular disease (type 4). A remarkable interest has also been placed on the acute and chronic systemic conditions, such as sepsis and diabetes, which simultaneously affect heart and kidney function (type 5). Furthermore, the physiology of acute and chronic heart-kidney cross talk is drawing attention to hemodynamics (fluids, pressures, flows, resistances, perfusion), physiochemical (electrolytes, pH, and toxins), and biological (inflammation, immune system activation, neurohormonal signals) processes. Common clinical scenarios call for recognition, knowledge, and skill in managing CRS. There is a clear need for medical and surgical specialists that are well versed in the pathophysiology and the clinical manifestations that arise in the setting of CRS. With this editorial, we are making a call to action to stimulate universities, medical schools, and teaching hospitals to create a core curriculum for cardiorenal medicine to better equip the physicians of the future for these common, serious, and frequently fatal syndromes.

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“…RTCs incubated with CRS type 5 plasma showed significantly higher apoptosis and necrosis levels compared with controls, with activation of caspase-3, caspase-8, and caspase-9 [44]. A possible relationship between endotoxin levels and renal cell death in septic patients with CRS type 5 has been suggested by the same authors [45]. RTCs incubated with plasma from endotoxin-positive patients showed significantly higher apoptosis levels and higher caspase-3 activation compared to cells incubated with plasma from endotoxin-negative patients, and a significant positive correlation was observed between endotoxin levels and RTC apoptosis levels [45 ](Table 1).…”

Section: Endotoxin Effects In Crs Typementioning

confidence: 99%

The Role of Endotoxin in the Setting of Cardiorenal Syndrome Type 5

et al. 2017

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Lipopolysaccharide or endotoxin, the major cell wall component of gram-negative bacteria, plays a pivotal role in the pathogenesis of sepsis. It is able to activate the host defense system through the interaction with Toll-like receptor 4, thus triggering pro-inflammatory mechanisms. When the production of inflammatory mediators becomes uncontrolled and excessive, septic shock develops with multiple organ dysfunction, such as myocardial and renal impairment, which are hallmarks of cardiorenal syndrome type 5. In this review, we will analyze the role of endotoxin in the pathogenesis of sepsis, its effects on cardiac and renal interactions in the setting of cardiorenal syndrome type 5 and the possible use of extracorporeal therapies in this clinical condition.

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Cardiorenal Syndrome Type 5 in Sepsis: Role of Endotoxin in Cell Death Pathways and Inflammation

Cited by 23 publications

References 27 publications

Chelerythrine Attenuates Renal Ischemia/ Reperfusion-induced Myocardial Injury by Activating CSE/H2S via PKC/NF-κB Pathway in Diabetic Rats

Chelerythrine Attenuates Renal Ischemia/ Reperfusion-induced Myocardial Injury by Activating CSE/H2S via PKC/NF-κB Pathway in Diabetic Rats

A Call to Action to Develop Integrated Curricula in Cardiorenal Medicine

The Role of Endotoxin in the Setting of Cardiorenal Syndrome Type 5

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