Endothelial Cell Activation in Muscle Biopsy Samples Is Related to Clinical Severity in Human Cerebral Malaria

García, Felipe; Cebrián, Mireia; Dgedge, Martinho; Casademont, Jordi; Bedini, José Luis; Neves, Otilia; Filella, Xavier; Cid, María C.; Corachán, M; Grau, Josep M.

doi:10.1086/314598

Cited by 17 publications

(18 citation statements)

References 23 publications

(25 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Widespread up-regulation of adhesion receptors ICAM-1 and E-selectin in cerebral vessels has supported the view of endothelial activation in fatal malaria [16], as well as a subsequent study that demonstrated a positive correlation between disease severity and induction of TNF, ICAM-1, VCAM-1, E-selectin and P-selectin in muscle biopsies, indicating widespread systemic EC activation [46].…”

Section: Direct Activation Of Ecsmentioning

confidence: 85%

Host response to cytoadherence inPlasmodium falciparum

Chakravorty

Hughes

Craig

2008

Biochemical Society Transactions

View full text Add to dashboard Cite

Cytoadherence of PRBCs (Plasmodium falciparum-infected red blood cells) to host endothelium has been associated with pathology in severe malaria, but, despite extensive information on the primary processes involved in the adhesive interactions, the mechanisms underlying the disease are poorly understood. Endothelial cells have the ability to mobilize immune and pro-adhesive responses when exposed to both PRBCs and TNF (tumour necrosis factor). In addition, there is also an up-regulation by PRBCs and TNF and a concurrent down-regulation of a range of genes involved in inflammation and cell death, by PRBCs and TNF. We propose that the balance between positive and negative regulation will contribute to endothelial pathology during malarial infection. Apposition of PRBCs has been shown by a number of groups to activate signalling pathways. This is dependent, at least in part, on the cytoadherence characteristics of the invading isolate, such that the avidity of the PRBC for the receptor on host endothelium is proportional to the level of activation of the signalling pathways. An understanding of the post-adhesive processes produced by cytoadherence may help us to understand the variable pathology seen in malaria and to design appropriate therapies to alleviate severe disease.

show abstract

Section: Direct Activation Of Ecsmentioning

confidence: 85%

Host response to cytoadherence inPlasmodium falciparum

Chakravorty

Hughes

Craig

2008

Biochemical Society Transactions

View full text Add to dashboard Cite

show abstract

“…Because it is not possible to access brain endothelium in life, to demonstrate the relevance of this IE-associated endothelial pathology in vivo, a surrogate tissue was required. Previous severe malaria studies have employed immunostaining on dermal 38 or muscle 39 biopsies, but these tissues lacked either endothelial activation 38 or IE sequestration 39 even in severe disease. We used subcutaneous biopsies, which exhibited both endothelial activation and IE sequestration, to demonstrate that EPCR and TM are reduced in CM in vivo.…”

Section: Blood 1 August 2013 X Volume 122 Number 5 Loss Of Protein mentioning

confidence: 99%

Loss of endothelial protein C receptors links coagulation and inflammation to parasite sequestration in cerebral malaria in African children

Moxon

Wassmer

Milner

et al. 2013

Blood

196

229

View full text Add to dashboard Cite

Cerebral malaria (CM) is a major cause of mortality in African children and the mechanisms underlying its development, namely how malaria-infected erythrocytes (IEs) cause disease and why the brain is preferentially affected, remain unclear. Brain microhemorrhages in CM suggest a clotting disorder, but whether this phenomenon is important in pathogenesis is debated. We hypothesized that localized cerebral microvascular thrombosis in CM is caused by a decreased expression of the anticoagulant and protective receptors thrombomodulin (TM) and endothelial protein C receptor (EPCR) and that low constitutive expression of these regulatory molecules in the brain make it particularly vulnerable. Autopsies from Malawian children with CM showed cerebral fibrin clots and loss of EPCR, colocalized with sequestered IEs. Using a novel assay to examine endothelial phenotype ex vivo using subcutaneous microvessels, we demonstrated that loss of EPCR and TM at sites of IE cytoadherence is detectible in nonfatal CM. In contrast, although clotting factor activation was seen in the blood of CM patients, this was compensated and did not disseminate. Because of the pleiotropic nature of EPCR and TM, these data implicate disruption of the endothelial protective properties at vulnerable sites and particularly in the brain, linking coagulation and inflammation with IE sequestration. (Blood. 2013;122(5):842-851)

show abstract

“…The injured skeletal muscles has biomarkers relating with severity of falciparum malaria infection [16, 21, 22], and the sequestration of infected red blood cells has been pointed out as the cause for these processes. Pronounced deviation in normal serum levels of creatine kinase (CK) have been also reported in malaria patients, affecting skeletal muscles [16, 21].…”

Section: Malaria Affecting Skeletal Musclesmentioning

confidence: 99%

The effect of malaria and anti-malarial drugs on skeletal and cardiac muscles

Marrelli

Brotto

2016

Malar J

View full text Add to dashboard Cite

Malaria remains one of the most important infectious diseases in the world, being a significant public health problem associated with poverty and it is one of the main obstacles to the economy of an endemic country. Among the several complications, the effects of malaria seem to target the skeletal muscle system, leading to symptoms, such as muscle aches, muscle contractures, muscle fatigue, muscle pain, and muscle weakness. Malaria cause also parasitic coronary artery occlusion. This article reviews the current knowledge regarding the effect of malaria disease and the anti-malarial drugs on skeletal and cardiac muscles. Research articles and case report publications that addressed aspects that are important for understanding the involvement of malaria parasites and anti-malarial therapies affecting skeletal and cardiac muscles were analysed and their findings summarized. Sequestration of red blood cells, increased levels of serum creatine kinase and reduced muscle content of essential contractile proteins are some of the potential biomarkers of the damage levels of skeletal and cardiac muscles. These biomarkers might be useful for prevention of complications and determining the effectiveness of interventions designed to protect cardiac and skeletal muscles from malaria-induced damage.

show abstract

Endothelial Cell Activation in Muscle Biopsy Samples Is Related to Clinical Severity in Human Cerebral Malaria

Cited by 17 publications

References 23 publications

Host response to cytoadherence inPlasmodium falciparum

Host response to cytoadherence inPlasmodium falciparum

Loss of endothelial protein C receptors links coagulation and inflammation to parasite sequestration in cerebral malaria in African children

The effect of malaria and anti-malarial drugs on skeletal and cardiac muscles

Contact Info

Product

Resources

About