The present study first demonstrates that CTRP-3 concentrations are significantly decreased in patients with ACS or SAP compared to control subjects even after adjusting for other confounding factors. However, circulating progranulin levels were not significantly different between patients with CAD and control subjects.
Adiponectin is a representative adipokine that possess insulin sensitizing, anti-inflammatory, and anti-atherogenic properties . Lower blood adiponectin levels are found in subjects with obesity, type 2 diabetes and metabolic syndrome. In a prospective cohort study for 3 years, we have shown that reduced adiponectin levels are independently associated with increased risk of both type 2 diabetes and metabolic syndrome . Administration of adenovirus-mediated adiponectin reduces atherosclerotic lesion size in apolipoprotein E knockout mice . Moreover, circulating adiponectin was shown to be lower in patients with CAD not only in cross-sectional studies , but also in prospective longitudinal studies . However, some other studies did not found a value of adiponectin as a predictor of cardiovascular events. Two prospective studies found no significant association in either American Indians  or British women . A meta-analysis has concluded that association between adiponectin and risk of coronary heart disease (CHD) is comparatively moderate, in contrast to the strong association between adiponectin and risk of type 2 diabetes . Recently, Kim et al. demonstrated that neither adiponectin nor interleukin-6 predicted angiographic coronary artery disease in the presence of diabetes . Furthermore, Baldasseroni et al. reported that adiponectin rises in patient with advanced heart failure, but this phenomenon is less evident in patients with type 2 diabetes . The present study did not show significant difference of adiponectin levels between patients with ACS or SAP and control subjects, although adiponectin levels were negatively correlated with several cardiometabolic risk parameters reflecting obesity, dyslipidemia, hyperglycemia and inflammation.
Despite the wide range of beneficial effects of adiponectin, adiponectin-deficient animal models show a relatively modest phenotype unless metabolically challenged, whereas adiponectin transgenic mice show distinct improvements in the metabolic phenotypes. Therefore, this discrepancy suggests the existence of compensatory mechanisms that partially counteract the deficiency of adiponectin [29, 30]. Recently, a novel family of adiponectin paralogs, designated C1q/TNF-related proteins (CTRPs), was discovered. Previous studies suggest the role of CTRP family proteins linking inflammation to metabolism . CTRP-3 is expressed in human subcutaneous and visceral adipocytes, and plays an important role in adipocyte physiology . CTRP-3 is a potent anti-inflammatory adipokine that inhibits pro-inflammatory signaling provoked by lipopolysaccharides (LPS), toll-like receptor (TLR) and fatty acids in adipocytes and monocytes . CTRP-3 reduces tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) secretion in LPS-treated monocytic cells through suppression of nuclear factor κB (NFκB) signaling pathway . Interestingly, CTRP-3 directly stimulates adiponectin and resistin release, and serves as a regulator of adiponectin secretion in adipocytes . In this study, circulating CTRP-3 levels showed a positive relationship with adiponectin and a negative relationship with hsCRP.
CTRP-3 has been reported to stimulate endothelial cell proliferation and migration in vitro . Recently, Yi et al. demonstrated for the first time that expression and production of CTRP-3 are significantly reduced after MI and that administration of CTRP-3 improves survival and restores cardiac function in mice with coronary artery occlusion . Therefore, they concluded that CTRP-3 is an adipokine possessing strong anti-remodeling and cardioprotective properties . In agreement with the previous animal study, the present study showed significantly decreased CTRP-3 levels in patients with ACS or SAP compared to control subjects. Adjustment for cardiovascular risk factors further strengthens the relationship between CTRP-3 levels and CAD. Yi et al. suggested that preventing post-MI CTRP-3 inhibition or CTRP-3 supplementation may be a promising therapeutic approach for creating stable and functional vessels .
We previously identified progranulin as a novel marker of chronic inflammation in obesity and type 2 diabetes that reflect macrophage infiltration in omental adipose tissue . Progranulin is recently re-discovered as an adipokine induced by TNF-α and dexamethasone . Progranulin in blood and adipose tissue was dramatically increased in obese mouse models and progranulin deficient mice protected from high fat diet (HFD)-induced insulin resistance, adipocytes hypertrophy and obesity . Pradeep et al. reported increased circulating progranulin and hsCRP levels in patients with obese subjects with chronic periodontitis, which is known as a risk factor for CAD . In an immunohistochemical analysis of human carotid endarterectomy specimens, both macrophages and vascular smooth muscle cells in atherosclerotic plaque express progranulin . Yilmaz et al. reported that patients with non-alcoholic fatty liver disease (NAFLD) have higher serum progranulin concentrations, which are positively associated with total cholesterol and LDL-cholesterol . Recently, Qu et al. reported that plasma progranulin levels were higher in Chinese patients with type 2 diabetes and correlated with insulin resistance, inflammation and glycolipid metabolism . In this study, progranulin concentrations showed modest negative relationship with HDL-cholesterol. Furthermore, patients with ACS or SAP did not show significant difference in progranulin levels compared to control subjects. Richter et al. reported that serum progranulin levels increase with deteriorating renal function . However, adjusting for confounding factors including eGFR or creatinine levels did not affect the relationship between progranulin concentration and CAD in the present study. Previous studies suggest the complex dual role of progranulin that exerts anti-inflammatory and pro-inflammatory functions depending on target tissue. Tang et al. reported that progranulin binds directly to TNF receptors (TNFRs) and interfering the interaction between TNF-α and TNFR . Full-length progranulin is generally anti-inflammatory, whereas proteolytically released granulins may have the opposite effect . Further studies about the association between progranulin and atherosclerosis might be needed.
Some limitations of the study need to be considered. First, this is a cross-sectional analysis which restricts us to draw causal conclusions. Secondly, this study enrolled only Asian men and women. Therefore, the results of the present study may not apply to other ethnic populations.