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1 Pharmacia Corporation, St. Louis, Missouri 63167; and 2 Cardiovascular and Metabolic Diseases, 3 Investigative Toxicology, 4 Biotechnology 5 Department of Veterinary Pathobiology, Purdue University, West Lafayette, Indiana 47907
Heart failure is a complex
multifactorial disease resulting in a myriad of progressive
changes at the molecular, cellular, and physiological level. To better
understand the mechanisms associated with the development of congestive
heart failure, a comprehensive examination of the aging lean male
spontaneously hypertensive, heart failure-prone rat (SHHF) was
conducted. Myocardial function and structural integrity progressively
diminished as evidenced by decreased ejection fraction and increased
left ventricular volume measured using echocardiography. Functional and
structural changes were accompanied by elevations in circulating
inflammatory markers, including tumor necrosis factor-
(TNF-),
IL-6, and TNF receptors type 1 and 2. Increased systemic inflammatory
marker levels were consistent with age-dependent changes in the
expression pattern of genes that contribute to stress, inflammation,
and the extracellular matrix in SHHF animals analyzed from age 4 to 18 mo. In summary, the SHHF rat shares many hallmark features of the
human disease state and represents a key experimental model for
the dissection of complex human heart failure pathophysiology.
echocardiography; inflammation; cytokines
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