Treatment of experimental myocarditis via modulation of the renin-angiotensin system.
The renin-angiotensin system is primarily responsible for regulating vascular tone. Drugs that inhibit this pathway, angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists, are widely used to treat hypertension and a variety of cardiomyopathies. Recent studies have shown that, in addition to reducing blood pressure, these drugs also modulate inflammation, adhesion molecule expression, and fibrosis. To assess the therapeutic potential of these inhibitory agents for the treatment of inflammatory heart disease, the drugs have been tested in experimental models of infectious and autoimmune myocarditis. This review summarizes the results of studies examining the efficacy of angiotensin converting enzyme inhibitors and angiotensin receptor antagonists for the treatment of mouse models of virus-induced and parasite-induced myocarditis, as well as autoimmune cardiomyopathy. The collective results strongly support the use of renin-angiotensin modulation for the treatment of myocarditis. Importantly, this therapeutic approach seems to downregulate autoimmunity without causing immune suppression which may enhance the survival of the disease-initiating infectious agent.
Daniels
Melvin D
MD
Department of Pathology and Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. d-engman@northwestern.edu
Hyland
Kenneth V
KV
Engman
David M
DM
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D009205:Myocarditis / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D011945:Receptors, Angiotensin; D007703:Peptidyl-Dipeptidase A