Heart-bound adiponectin, not serum adiponectin, inversely correlates with cardiac hypertrophy in stroke-prone spontaneously hypertensive rats

Abstract

The inverse correlation between circulating adiponectin concentration and hypertension or cardiac hypertrophy is still controversial. In addition to circulating adiponectin, adiponectin is also bound to tissues such as the heart and skeletal muscle. In this study, we investigated the relationship of serum adiponectin and heart-bound adiponectin to hypertension and cardiac hypertrophy. Four types of hypertensive rats presenting different blood pressure levels were used at different ages: normotensive Wistar-Kyoto rats (WKY); two sub-strains (strains C and B2, having low and high blood pressure, respectively) of spontaneously hypertensive rats (SHR); and stroke-prone SHR (SHRSP). Blood pressure, heart/body weight ratio, serum adiponectin, and heart-bound adiponectin were determined. Histopathological analysis of the heart was carried out to evaluate the relationship with heart-bound adiponectin. Serum adiponectin concentration did not inversely correlate with blood pressure or heart/body weight ratio. In contrast, heart-bound adiponectin levels were significantly lower in SHRSP than in other strains at respective ages. This resulted from a decrease in T-cadherin expression, which induced adiponectin binding to tissues. No significant difference in heart-bound adiponectin among WKY and SHR (C and B2) was detected, indicating that heart-bound adiponectin is not related to hypertension. In addition, differences in heart-bound adiponectin did not affect AMP-activated protein kinase in the traditional adiponectin activation cascade. Histopathological analysis revealed that heart-bound adiponectin inversely correlated with cardiomyocyte hypertrophy and left ventricular wall thickness, and partially with cardiac fibrosis. These results suggest that the decreased level of heart-bound adiponectin in SHRSP is more related to their cardiac hypertrophy than circulating adiponectin.

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