Structural, functional, and molecular characterization of the SHHF model of heart failure.
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-alpha (TNF-alpha), 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.
Heyen
Jonathan R R
JR
Pharmacia Corporation, 800 N. Lindbergh Boulevard, St. Louis, MO 63167, USA. Jonathan.R.Heyen@PHARMACIA.com
Blasi
Eileen R
ER
Nikula
Kristen
K
Rocha
Ricardo
R
Daust
Heather A
HA
Frierdich
Gregory
G
Van Vleet
John F
JF
De Ciechi
Pam
P
McMahon
Ellen G
EG
Rudolph
Amy E
AE
D000818:Animals; D015415:Biomarkers; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D004452:Echocardiography; D016326:Extracellular Matrix Proteins / Q000235:genetics; D015870:Gene Expression; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D051381:Rats; D011922:Rats, Mutant Strains; D013318:Stroke Volume; D014158:Transcription, Genetic
D015415:Biomarkers; D016207:Cytokines; D016326:Extracellular Matrix Proteins