Role of Endothelin 1 in the Pathogenesis of Chronic Chagasic Heart Disease

Tanowitz, Herbert B.; Huang, Huan; Jelicks, Linda A.; Chandra, Madhulika; Loredo, Maria; Weiss, Louis M.; Factor, Stephen M.; Shtutin, Vitaliy; Mukherjee, Shankar; Kitsis, Richard N.; Christ, George J.; Wittner, Murray; Shirani, Jamshid; Kisanuki, Yaz Y.; Yanagisawa, Masashi

doi:10.1128/iai.73.4.2496-2503.2005

Cited by 84 publications

(88 citation statements)

References 60 publications

(80 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This vasculopathy is manifest in humans and animals by vasospasm, reduced blood flow, focal ischemia, platelet thrombi, increased platelet aggregation, and elevated plasma levels of thromboxane A 2 and endothelin-1. [57][58][59] These findings indicate the possibility of using the guinea pig to examine this novel aspect of Chagas cardiac pathogenesis. The guinea pig model has already been used for the testing of vaccines for T. cruzi and other infections.…”

Section: Discussionmentioning

confidence: 96%

Cavia porcellus as a Model for Experimental Infection by Trypanosoma cruzi

Castro-Sesquen

Gilman

Yauri

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

The guinea pig (Cavia porcellus) is a natural reservoir for Trypanosoma cruzi but has seldom been used as an experimental infection model. We developed a guinea pig infection model for acute and chronic Chagas disease. Seventy-two guinea pigs were inoculated intradermally with 10 4 trypomastigotes of T. cruzi strain Y (experimental group); 18 guinea pigs were used as control group. Eight animals from the experimental group and two from the control group were Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is one of the most important parasitic infections of the Americas. Despite successful vector control programs in many countries, the disease remains a major public health problem in Latin America, with 8 to 10 million people currently infected, an annual incidence of 65,000 new cases in 15 countries, and 14,000 deaths associated with the infection per year. 1 Transmission to the mammalian host occurs when a T. cruzi-infected triatomine vector deposits infectious trypomastigotes in feces during a blood meal and the parasites invade through the bite wound or intact mucosal membranes. 2 Trypomastigotes can infect virtually any nucleated cell, where they transform to amastigotes and replicate in the host cell cytoplasm. Amastigotes convert back to trypomastigotes inside the cell and then rupture the cell and circulate in the bloodstream. After weeks, the host immune response usually controls the acute infection but does not completely clear the parasite. This results in lifelong chronic infection of the host.The initial weeks after T. cruzi infection are characterized by a high-level parasitemia and symptoms that vary from mild nonspecific febrile illness to life-threatening myocarditis and/or meningoencephalitis. 2 Acute symptoms and detectable parasitemia resolve spontaneously within 2 to 3 months, and the infected individual passes into the chronic phase of the disease. Nearly all individuals in the early period of chronic infection are asymptomatic and are said to have the indeterminate form of the disease. In most individuals, the infection remains silent for life and is detectable only by anti-T. cruzi serologic tests and, in a proportion of individuals, by molecular Supported by NIH training grant in infectious and tropical diseases 5 T35 AI065385 and NIH grant 1R01AI087776-01.

show abstract

Section: Discussionmentioning

confidence: 96%

Cavia porcellus as a Model for Experimental Infection by Trypanosoma cruzi

Castro-Sesquen

Gilman

Yauri

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…Experimental studies on Chagas disease in mice have demonstrated microvascular alterations characterized by microspasms (Factor et al, 1985), microthrombi (de Oliveira et al, 2007;Samuel et al, 1983;Tanowitz et al, 1990), dysfunction of endothelial cells and increased platelet activity (Petkova et al, 2001;Tanowitz et al, 2005). There is direct interaction between platelets and inflammated endothelium when it is activated (Danese et al, 2007;Tanowitz et al, 2005) (Danese et al, 2007), for example, by T. cruzi infection.…”

Section: Microvascular Abnormalities and Ischemiamentioning

confidence: 99%

“…Endothelin mediates arteriolar spasm and inhibits cAMP, with consequent stimulation of platelet adhesion to the vascular wall. There is evidence of increased production of endothelin in Chagas disease (Tanowitz et al, 2005). Many of the sequelae associated with T. cruzi infection are reminiscent of the effects of TXA2, including enhanced platelet adherence and aggregation in T cruzi-infected mice, where TXA2 levels are increased (Ashton et al, 2007;Cardoni and Antunez, 2004;Tanowitz et al, 1990).…”

Section: Microvascular Abnormalities and Ischemiamentioning

confidence: 99%

“…There is direct interaction between platelets and inflammated endothelium when it is activated (Danese et al, 2007;Tanowitz et al, 2005) (Danese et al, 2007), for example, by T. cruzi infection. However, endothelial function may be preserved in patients without heart failure (Consolim- Colombo et al, 2004;Tanowitz et al, 2009).…”

Section: Microvascular Abnormalities and Ischemiamentioning

confidence: 99%

See 1 more Smart Citation

Chagas disease: Present status of pathogenic mechanisms and chemotherapy

et al. 2010

View full text Add to dashboard Cite

There are approximately 7.8 million people in Latin America, including Chile, who suffer from Chagas disease and another 28 million who are at risk of contracting it. Chagas is caused by the flagellate protozoan Trypanosoma cruzi. It is a chronic disease, where 20%-30% of infected individuals develop severe cardiopathy, with heart failure and potentially fatal arrhythmias. Currently, Chagas disease treatment is more effective in the acute phase, but does not always produce complete parasite eradication during indeterminate and chronic phases. At present, only nifurtimox or benznidazole have been proven to be superior to new drugs being tested. Therefore, it is necessary to find alternative approaches to treatment of chronic Chagas. The current treatment may be rendered more effective by increasing the activity of anti-Chagasic drugs or by modifying the host's immune response. We have previously shown that glutathione synthesis inhibition increases nifurtimox and benznidazole activity. In addition, there is increasing evidence that cyclooxygenase inhibitors present an important effect on T. cruzi infection. Therefore, we found that aspirin reduced the intracellular infection in RAW 264.7 cells and, decreased myocarditis extension and mortality rates in mice. However, the long-term benefit of prostaglandin inhibition for Chagasic patients is still unknown.

show abstract

“…In vitro studies of T. cruzi infection of human umbilical vein endothelium cells showed increased production of endothelin. This potent vasoconstrictor mediated arteriolar spasm and impaired cyclic adenosine monophosphate (AMP) metabolism, thus impairing AMP's protective role against platelet adhesion to and aggregation along the vascular wall 28,29 . Trypomastigote forms of T. cruzi also produce a neuraminidase that may remove sialic acid from the surface of mammalian myocardial and endothelial cells 30 .…”

Section: Evidence From Animal Models Of T Cruzi Infection and In Vitmentioning

confidence: 99%

Pathogenesis of chronic Chagas cardiomyopathy: the role of coronary microvascular derangements

Marin-Neto

Simões

Rassi

2013

Rev. Soc. Bras. Med. Trop.

View full text Add to dashboard Cite

There is ample experimental and clinical evidence of functional and structural microvascular abnormalities occurring in patients with Chagas cardiomyopathy, possibly due to the infl ammatory process and/or autonomic disturbances caused by Trypanosoma cruzi infection. Those microvascular derangements are likely to constitute at least an ancillary factor that potentiates and amplifi es the chronic infl ammation in myocardial tissue. It is possible to devise appropriate therapeutic interventions aimed at reverting or slowing the progression of the microvascular abnormalities to positively affect the natural history of Chagas cardiomyopathy.

show abstract

Role of Endothelin 1 in the Pathogenesis of Chronic Chagasic Heart Disease

Cited by 84 publications

References 60 publications

Cavia porcellus as a Model for Experimental Infection by Trypanosoma cruzi

Cavia porcellus as a Model for Experimental Infection by Trypanosoma cruzi

Chagas disease: Present status of pathogenic mechanisms and chemotherapy

Pathogenesis of chronic Chagas cardiomyopathy: the role of coronary microvascular derangements

Contact Info

Product

Resources

About