Impaired Expression of Cardiac Adiponectin in Leptin-Deficient Mice With Viral Myocarditis

Abstract

SUMMARYA mouse model of encephalomyocarditis (EMC) virus-induced myocarditis was used to investigate the expression of adiponectin in damaged cardiomyocytes. We intraperitoneally injected EMC virus into leptin-deficient ob/ob (OB) mice and wild-type (WT) mice. OB mice were divided into two subgroups consisting of mice with no intervention and mice receiving leptin replacement starting simultaneously with viral inoculation. We determined differences in heart weight, cardiac histological score, numbers of infiltrating and apoptotic cells in the myocardium, expression levels of adiponectin and TNF-α mRNA in the heart, adiponectin immunoreactivity in myocytes, adiponectin and TNF-α concentrations in the heart, and immunoreactivity of adiponectin receptors in myocytes between OB mice and WT mice. There was significantly decreased adiponectin mRNA expression, immunoreactivity, and protein level in the heart, and reduced immunoreactivity of adiponectin receptor 1 in myocytes from OB mice on days 4 and 8 after viral inoculation as compared with those in WT mice, together with increased cardiac weight, severe inflammatory myocardial damage, and increased levels of cardiac TNF-α mRNA and protein. Replacement of leptin in OB mice inhibited the development of severe myocarditis through augmentation of adiponectin mRNA, immunoreactivity, and protein level, increased adiponectin receptor 1 immunoreactivity in myocytes, and suppressed levels of TNF-α mRNA and protein. These results suggest that impaired expression of cardiac adiponectin may contribute to the progression of viral myocarditis through enhanced expression of TNF-α under a leptin-deficient condition. (Int Heart J 2006; 47: 107-123) Key words: Adiponectin, Leptin deficiency, Viral myocarditis, Cardiomyocyte HEART failure is generally considered to begin with myocyte damage caused by a variety of pathological conditions that include ischemia, toxins, and myocardial infection. The heart compensates by dilatation and cellular hypertrophy, and eventually decompensates, resulting in heart failure. A proinflammatory cytokFrom the

The Effects of a PPAR<i>&alpha;</i> Agonist on Myocardial Damage in Obese Diabetic Mice With Heart Failure

“…13) In agreement with this previous study, we found that adiponectin mRNA expression levels were markedly higher in WY14643-treated mice on days 0, 4, and 9, and that the myocardial diameter decreased and the inflammation improved. These findings imply that the adiponectin-associated antihypertrophic and anti-inflammatory effects might be involved in WY14643 treatment of EMCv-inoculated KKAy mice.…”

“…Some slices were stained with hematoxylin-eosin to assess the severity of myocardial necrosis and inflammatory cell infiltration according to previously described scales. 13,14) The LV wall thickness (LW) and LV cavity (LC) dimensions were measured with the slice at the maximal circumference of the ventricle, as described by Matsumori, et al 15) (Figure 1). The diameter of the myocardial fiber in the lateral LV wall was determined as described previously.…”

“…11) In previous studies, we inoculated EMCv into obese mice to set up a model of obese mice with severe heart failure, and found higher TNF-α and lower adiponectin expression levels in the injured myocardium. 12,13) Herein, obese diabetic KKAy mice inoculated with EMCv were used to induce a model of type 2 diabetes and obesity complicated with severe heart failure, and subsequently to evaluate the effect of WY14643. We determined the survival rate and examined the expression levels of cardiac TNF-α, adiponectin, and UCP3 at different stages of myocardial damage and found that WY14643 plays different roles in the injured heart.…”

Inverse Relationship Between Adiponectin Levels and Subclinical Carotid Atherosclerosis in Patients Undergoing Coronary Artery Bypass Grafting

“…34) In addition, Takahashi, et al found that impaired expression of cardiac adiponectin may contribute to the progression of viral myocarditis through enhanced expression of TNF-α in leptin-deficient mice. 35) They speculated that local expression of adiponectin in the damaged heart may be a compensatory phenomenon against severe inflammatory conditions such as viral myocarditis. 35) These anti-inflammatory effects of adiponectin may contribute to its protective features against the development of atherosclerosis.…”

“…35) They speculated that local expression of adiponectin in the damaged heart may be a compensatory phenomenon against severe inflammatory conditions such as viral myocarditis. 35) These anti-inflammatory effects of adiponectin may contribute to its protective features against the development of atherosclerosis. Conclusions: In conclusion, our findings indicate an inverse relation exists between serum concentrations of adiponectin and subclinical carotid atherosclerosis in patients undergoing CABG.…”