1. Cardiac Failure in C5-Deficient A/J Mice afterCandida albicansInfection
- Author
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Rita Lo, Eugene Daniels, Zully Leon, Alaka Mullick, Joanne Berghout, Gundula Min-Oo, and Philippe Gros
- Subjects
medicine.medical_specialty ,Heart Diseases ,Mice, Inbred A ,Immunology ,Cardiomyopathy ,PDK4 ,Inflammation ,Microbiology ,Mice, Congenic ,Mice ,Internal medicine ,Candida albicans ,medicine ,Animals ,Crosses, Genetic ,Oligonucleotide Array Sequence Analysis ,biology ,Gene Expression Profiling ,Myocardium ,Candidiasis ,Cardiac muscle ,Complement C5 ,Proteins ,Heart ,medicine.disease ,Pyruvate dehydrogenase complex ,biology.organism_classification ,Mice, Inbred C57BL ,Infectious Diseases ,Endocrinology ,medicine.anatomical_structure ,Heart failure ,biology.protein ,Cytokines ,Parasitology ,Creatine kinase ,Fungal and Parasitic Infections ,medicine.symptom ,Biotechnology - Abstract
The effect of a deficiency in the C5 component of complement on the pathophyisology of infection with the fungal pathogenCandida albicanswas studied by using the A/J inbred mouse strain and the BcA17 congenic mouse strain. Acute infection caused by intravenous injection ofC. albicansblastospores is associated with rapid fungal replication in the heart, brain, and, in particular, kidneys of C5-deficient mice. Histological studies and analysis of markers for tissue damage indicated that the heart is the organ that is most affected and that it ultimately fails in C5-deficient mice. In A/J and BcA17 mice, tissue damage is associated with (i) cellular infiltration in the heart, which is not seen in the kidney despite the higher fungal load in the latter organ, and (ii) a very strong inflammatory response, including elevated levels of many cytokines and chemokines. This results in cardiomyopathy, which is associated with elevated levels of creatine kinase and cardiac troponin I in the circulation. Damage to the cardiac muscle is associated with metabolic changes, including hypoglycemia, decreased lipid utilization resulting in elevated levels of cardiac triglycerides, and unproductive glucose utilization linked to a dramatic increase in the level of pyruvate dehydrogenase kinase 4 (Pdk4), a negative regulator of the pyruvate dehydrogenase complex.
- Published
- 2006