Evaluation of immunomodulatory biomarkers in a pressure overload model of heart failure.
OBJECTIVE
To characterize the immunomodulatory response in a pressure overload model of heart failure, and to further validate this animal model of human heart failure.


METHODS
Randomized, controlled, animal study.


METHODS
Large university research facility.


METHODS
Twenty-seven, male, Sprague-Dawley rats.


METHODS
The rats underwent either aortic constriction or a sham procedure.


RESULTS
Six months after the surgical procedure, echocardiographic measurements were obtained, the animals were sacrificed, and plasma samples were taken to measure concentrations of biomarkers. As six (40%) of the 15 rats in the aortic-constriction group died before the 6 months, only nine rats from this group underwent immunomodulatory evaluation. Compared with the sham procedure, aortic constriction increased the left ventricle:body weight ratio in the rats (p=0.0016) It also decreased the velocity of circumferential shortening (p=0.08) and increased myocardial expression of atrial natriuretic factor, beta-myosin heavy chain, and fibronectin (p<0.05). Concentrations of the proinflammatory mediator interleukin (IL)-1beta and the counterregulatory mediator IL-10 also significantly increased (p<0.04) in the group that underwent aortic constriction compared with the group that underwent the sham procedure. Nonsignificant increases (mean change approximately 50-180%) were also observed for IL-2, IL-6, and leptin concentrations.


CONCLUSIONS
In this classic animal model of heart failure, a systemic immunomodulatory response was evaluated after 6 months of pressure overload resulting in myocardial decompensation and, in some cases, mortality. The findings are similar to the immunomodulatory response that may be observed in human heart failure. These novel results further define this model of heart failure and suggest another aspect of its relevance to human heart failure with regard to pressure overload and the immunomodulatory response.
Bleske
Barry E
BE
College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065, USA.
Hwang
Hyun Seok
HS
Zineh
Issam
I
Ghannam
Michael G
MG
Boluyt
Marvin O
MO
D043925:Angiogenesis Inducing Agents / Q000097:blood / Q000378:metabolism; D000818:Animals; D001017:Aortic Coarctation / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000235:genetics; D015415:Biomarkers / Q000032:analysis*; D015152:Blotting, Northern; D004195:Disease Models, Animal; D004452:Echocardiography; D005353:Fibronectins / Q000097:blood / Q000235:genetics; D015870:Gene Expression; D006333:Heart Failure / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D007378:Interleukins / Q000097:blood / Q000235:genetics; D020738:Leptin / Q000097:blood / Q000235:genetics; D008297:Male; D018995:Myosin Heavy Chains / Q000097:blood / Q000235:genetics; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013997:Time Factors
D043925:Angiogenesis Inducing Agents; D015415:Biomarkers; D005353:Fibronectins; D018836:Inflammation Mediators; D007378:Interleukins; D020738:Leptin; D009320:Atrial Natriuretic Factor; D018995:Myosin Heavy Chains