Vitamin D and macrophage polarization in epicardial adipose tissue of atherosclerotic swine

Abstract

Vitamin D functions as a potent immunomodulator by interacting with many immune cells however, its role in regulating inflammation in the epicardial adipose tissue (EAT) is unclear. In the EAT of atherosclerotic microswine that were fed with deficient, sufficient or supplemented levels of vitamin D, we evaluated the phenotype of the macrophages. Vitamin D treatment was continued for 12 months and serum 25(OH)D levels were measured regularly. Infiltration of M1/M2 macrophage was investigated by immunostaining for CCR7 and CD206, respectively in conjunction with a pan macrophage marker CD14. Significant difference in the number of CCR7+ cells was observed in the EAT from vitamin D-deficient swine compared to vitamin D-sufficient or -supplemented swine. Expression of CD206 correlated with high levels of serum 25(OH)D indicating a significant increase in M2 macrophages in the EAT of vitamin D-supplemented compared to -deficient swine. These findings suggest that vitamin D-deficiency exacerbates inflammation by increasing pro-inflammatory M1 macrophages, while vitamin D-supplementation attenuates the inflammatory cytokines and promotes M2 macrophages in EAT. This study demonstrates the significance of vitamin D mediated inhibition of macrophage mediated inflammation in the EAT during coronary intervention in addition to its immunomodulatory role. However, additional studies are required to identify the cellular mechanisms that transduce signals between macrophages and smooth muscle cells during restenosis in the presence and absence of vitamin D.

Vitamin D: Nutrient, Hormone, and Immunomodulator

“…In addition to autoimmune diseases vitamin D has also been implicated in the control of other inflammatory conditions, such as cardiovascular diseases: in animal models vitamin D 3 administration reduces macrophage production of pro-inflammatory cytokines, and decreases atherosclerosis and inflammation in the epicardial adipose tissue [ 116 , 117 ]. In humans an association between low 25(OH)D 3 level and increased activation of inflammatory pathway in epicardial adipose tissuein patients affected by coronary artery disease has been described [ 118 ].…”

Sirtuin-1 and Its Relevance in Vascular Calcification

“…In obese rats fed a diet deficient in vitamin D, the expressions of Sirt1 and AMPK in adipose tissue were significantly decreased, and PPARγ was upregulated to induce macrophage polarization and infiltration [138]. It is reasonable that an adequate level of vitamin D supplement is beneficial in attenuating macrophage-induced inflammation in adipose tissue [139]. Vitamin D supplements in adipose tissue treated with high levels of glucose led to enhanced phosphorylated AMPK/Sirt1 expression and antioxidant enzyme-related Nrf2 transcription factor, and both stimulated GLUT4 expression, which increased glucose uptake in adipose tissue.…”

Cathepsin L expression in the carotid arteries of atherosclerotic swine

“…The cells from the second to fifth passages were used. The phenotype and the homogeneity of isolated SMCs were confirmed by positive staining for smooth muscle α-actin and caldesmon [10,11]. Once the cells were confluent, they were treated with CTSL, TGFB1 and cystatin C overnight.…”

“…The increased expression of CTSL in S plaques highlights the potential role of CTSL in plaque instability and needs further investigation in animal models.The porcine model is the most used and accepted model for cardiovascular diseases [9]. The same operative and imaging techniques used clinically in humans can be performed in swine [10,11]. Previous studies conducted in swine show morphology and physiology of the lesions in the carotid arteries comparable to humans [12,13].…”