Globular domain of adiponectin: promising target molecule for detection of atherosclerotic lesions.

BACKGROUND: Adiponectin, an adipocyte-specific plasma protein, has been shown to accumulate in injured endothelial cells during development of atherosclerotic lesions. In this study, we investigated the potential of different adiponectin subfractions with special emphasis on globular adiponectin (gAd) to recognize and visualize atherosclerotic lesions. METHODS: Recombinant mouse gAd and subfractions of full-length adiponectin (ie, trimeric, hexameric, and oligomeric forms) were fluorescence-labeled. Aortas of wild-type and apoprotein E-deficient mice fed a high cholesterol diet were dissected and incubated with the labeled biomarkers. Imaging was performed using confocal laser scanning microscopy. RESULTS: Confocal laser scanning microscopic images showed that gAd binds more strongly to atherosclerotic plaques than full-length adiponectin subfractions. Further, we showed that gAd accumulates preferentially in endothelial cells and the fibrous cap area of plaques. Here we demonstrate for the first time that gAd recognizes atherosclerotic plaques on aortic sections of apoprotein E-deficient mice. CONCLUSION: These results suggest that gAd, in addition to its physiological properties, is also suitable as a target molecule for prospective diagnostic strategies in imaging atherosclerotic lesions.

Adiponectin-coated nanoparticles for enhanced imaging of atherosclerotic plaques.

BACKGROUND: Atherosclerosis is a leading cause of mortality in the Western world, and plaque diagnosis is still a challenge in cardiovascular medicine. The main focus of this study was to make atherosclerotic plaques visible using targeted nanoparticles for improved imaging. Today various biomarkers are known to be involved in the pathophysiologic scenario of atherosclerotic plaques. One promising new candidate is the globular domain of the adipocytokine adiponectin (gAd), which was used as a targeting sequence in this study. METHODS: gAd was coupled to two different types of nanoparticles, namely protamine-oligonucleotide nanoparticles, known as proticles, and sterically stabilized liposomes. Both gAd-targeted nanoparticles were investigated for their potency to characterize critical scenarios within early and advanced atherosclerotic plaque lesions using an atherosclerotic mouse model. Aortic tissue from wild type and apolipoprotein E-deficient mice, both fed a high-fat diet, were stained with either fluorescent-labeled gAd or gAd-coupled nanoparticles. Ex vivo imaging was performed using confocal laser scanning microscopy. RESULTS: gAd-targeted sterically stabilized liposomes generated a strong signal by accumulating at the surface of atherosclerotic plaques, while gAd-targeted proticles became internalized and showed more spotted plaque staining. CONCLUSION: Our results offer a promising perspective for enhanced in vivo imaging using gAd-targeted nanoparticles. By means of nanoparticles, a higher payload of signal emitting molecules could be transported to atherosclerotic plaques. Additionally, the opportunity is opened up to visualize different regions in the plaque scenario, depending on the nature of the nanoparticle used.

Nuchal thickness of subcutaneous adipose tissue is tightly associated with an increased LMW/total adiponectin ratio in obese juveniles.

Subcutaneous adipose tissue (SAT) topography contributes significantly to metabolic risk profiles and atherosclerotic vascular burden in obese adults. However, little information exists concerning individual risk profiles in early phases of obesity found in childhood and adolescence. Thus, the rationale of this study was to evaluate possible impacts of SAT topography in obese juveniles on adiponectin subfractions, with special emphasis on low molecular weight (LMW) adiponectin. To address this, we analysed associations between lipometry, early metabolic and preatherosclerotic symptoms and adiponectin subfractions in 71 obese juveniles and 75 normal weight controls of similar age and gender distribution. Compared to the controls, obese juveniles had a significantly decreased ratio between high molecular weight (HMW) and total adiponectin whereas the LMW/total adiponectin ratio was increased. The LMW/total adiponectin ratio correlated significantly positively with the SAT thickness of trunk-located lipometer measure points neck, biceps, upper back, lower back, body mass index (BMI), and waist circumference. Further significant positive correlations were seen with systolic blood pressure, intima media thickness (IMT) of common carotid arteries, and metabolic parameters such as HOMA-index, leptin, oxidized LDL (oxLDL), liver transaminases, and HDL-triglycerides. This remained stable after controlling for gender. A stepwise multiple regression analysis encompassing all these variables revealed a robust positive association between LMW/total adiponectin ratio and nuchal SAT thickness defined by the lipometer measure point neck. Taken together, our data provide the first evidence that nuchal SAT thickness is tightly positively associated with an increased LMW/total adiponectin ratio.

Preatherosclerosis and adiponectin subfractions in obese adolescents.

We evaluated total adiponectin, high-molecular weight (HMW), medium-molecular weight (MMW), low-molecular weight (LMW) adiponectin subfractions, clinical parameters, routine lab parameters, lipids, metabolic, inflammatory biomarkers, and intima-media thickness (IMT) of common carotid arteries in 70 obese juveniles and adolescents with preatherosclerosis and 55 normal weight controls of similar age and gender distribution. Compared with the controls, the obese probands had a significantly increased IMT (P < 0.001) and elevated ultra-sensitive C-reactive protein (P < 0.001) indicating early vascular burden. Total and HMW adiponectin were significantly decreased in the obese cohort. The ratio between HMW and total adiponectin was significantly decreased in obese probands whereas the LMW/total adiponectin ratio was increased. Overall, total-, HMW, and MMW adiponectin were significantly negatively correlated with carotid IMT. The HMW/total adiponectin ratio correlated significantly negatively, and the LMW/total adiponectin ratio significantly positively with the IMT. Furthermore, HMW adiponectin was significantly positively correlated with high-density lipoprotein (HDL)-cholesterol and serum apolipoprotein A1, and negatively with BMI, triglycerides, homeostatic model assessment (HOMA)-index, leptin, liver transaminases, and uric acid. This remained stable after controlling for gender. Multiple regression analysis of body measures and all other lab parameters showed the strongest correlation between HMW adiponectin and carotid IMT (beta = -0.35, P < 0.001). Taken together, our study provides the first evidence that preatherosclerosis in obese juveniles and adolescents is associated with altered subfractions of adiponectin, whereas after multiple testing the HMW subfraction showed a better correlation to IMT compared with total adiponectin.