Abstract
The C1q/TNF-related protein 3 (CTRP3) represents a pleiotropic adipokine reciprocally associated with obesity and type 2 diabetes mellitus and exhibits anti-inflammatory properties in relation to lipopolysaccharides (LPS)-mediated effects in adipocytes, as well as monocytes/macrophages. Here, we focused on the influence of CTRP3 on LPS-mediated effects in endothelial cells in order to expand the understanding of a possible anti-inflammatory function of CTRP3 in a setting of endotoxemia. An organ- and tissue-specific expression analysis by real-time PCR revealed a considerable Ctrp3 expression in various adipose tissue compartments; however, higher levels were detected in the aorta and in abundantly perfused tissues (bone marrow and the thyroid gland). We observed a robust Ctrp3 expression in primary endothelial cells and a transient upregulation in murine endothelial (MyEND) cells by LPS (50 ng/mL). In MyEND cells, CTRP3 inhibited the LPS-induced expression of interleukin (Il)-6 and the tumor necrosis factor (Tnf)-α, and suppressed the LPS-dependent expression of the major endothelial adhesion molecules Vcam-1 and Icam-1. The LPS-induced adhesion of monocytic cells to an endothelial monolayer was antagonized by CTRP3. In C57BL/6J mice with an LPS-induced systemic inflammation, exogenous CTRP3 did not affect circulating levels of TNF-α, ICAM-1, and VCAM-1. In conclusion, we characterized CTRP3 beyond its function as an adipokine in a setting of vascular inflammation. CTRP3 inhibited LPS-induced endothelial expression of adhesion molecules and monocyte cell adhesion, indicating an important vascular anti-inflammatory role for CTRP3 in endotoxemia.
Highlights
Cardiovascular diseases represent a severe and worldwide health issue and are among the most common causes of premature death [1]
Ctrp3 expression was detected in adipose tissue: the highest level in mesenteric; followed by epididymal and subcutaneous tissue; and a rather low level expressed in thoracic, perirenal, and brown adipose tissue
The present study investigated the immune-regulatory functions of the pleiotropic adipokine C1q/tumor necrosis factor (TNF)-related protein 3 (CTRP3) from a perspective of cardiovascular biology, focusing on aspects of endothelial dysfunction
Summary
Cardiovascular diseases represent a severe and worldwide health issue and are among the most common causes of premature death [1]. Vascular endothelial dysfunction, representing a key element of many cardiovascular diseases, is often associated with and aggravated by metabolic dysregulation and adipose tissue inflammation, commonly referred to as metaflammation [4], in obesity [5]. Besides its classical physiological functions in energy storage and lipid metabolism, adipose tissue represents an important endocrine organ [6,7] and its role in immuneregulatory processes linking metabolism and inflammation/immunity has been increasingly recognized in recent years [8,9]. Among the ever-growing number of identified adipokines [10], representing secretory proteins which originate from adipocytes and exert paracrine and endocrine functions, C1q/TNF-related protein 3 (CTRP3) is an important and pleiotropic factor involved in both immunological and metabolic processes. Similar to its paralog adiponectin, systemic CTRP3 is negatively associated with obesity [11,12]
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