Tachycardia-induced primate model of heart failure in cardiovascular drug discovery.
Congestive heart failure (CHF) is a complex, multifactoral disease involving genetic and environmental factors that represents a large unmet medical need. There are currently many animal models of CHF that have provided some insight into the etiology of this disease. However, due to the complex interactions of environmental and genetic components of this disease most animal models are somewhat limited. Nonhuman primates offer a unique opportunity to investigate the genetic aspects of this complex disease due to their close genetic and phenotypic similarity to humans. Here we describe a novel tachycardia-induced primate model of CHF characterized by depressed global function that progresses to a symptomatic stage consistent with clinical data. No animal model, including this one, can exactly mimic the clinical pathophysiology of CHF. However, this tachycardia-induced primate model of CHF has similarities to the dynamic state of CHF in humans and affords the opportunity to evaluate changes in gene expression using genomic and proteomic technologies throughout the progression of the disease.
Smith
A H
AH
Department of Cardiovascular and Metabolic Diseases, Pfizer Central Research, Pfizer Inc., Eastern Point Road, Groton, CT 06340, USA.
Wolfgang
E A
EA
Flynn
D M
DM
Doe
C P
CP
Knight
D R
DR
D000818:Animals; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006333:Heart Failure / Q000188:drug therapy / Q000209:etiology*; D008252:Macaca fascicularis; D013610:Tachycardia / Q000150:complications*; D018487:Ventricular Dysfunction, Left / Q000209:etiology
D002317:Cardiovascular Agents