<p>The Association Between Sortilin and Inflammation in Patients with Coronary Heart Disease</p>

Abstract

Purpose: Inflammation is a key contributor to coronary heart disease (CHD). Sortilin is a sorting receptor and has been identified as a critical regulator of inflammatory response. Therefore, our study aimed to determine the link between circulating sortilin levels, proinflammatory cytokine levels, and the occurrence of CHD.Patients and Methods: Our study included 227 CHD patients and 101 matched healthy individuals. Circulating serum levels of sortilin and proinflammatory cytokines, including IL-1β, IL-6 and TNF-α, were assessed by a double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA). Linear regression and correlation analyses were used to estimate the associations between sortilin and proinflammatory cytokines. Moreover, six singlenucleotide polymorphisms (SNPs) spanning the sortilin and SORL1 genes were genotyped. Results: Elevated levels of sortilin (P=0.027) and proinflammatory cytokines IL-1β (P=0.013), IL-6 (P=0.000) and TNF-α (P=0.010) were observed in CHD patients compared to those in healthy controls. Furthermore, sortilin levels were significantly positively correlated with IL-1β (r=0.252, P=0.0001), IL-6 (r=0.250, P=0.0001) and TNF-α (r=0.180, P=0.0064) levels. Notably, sortilin polymorphisms were revealed to be associated with the occurrence of CHD and varying sortilin levels. Subjects with the rs599839 AA risk genotype for CHD had significantly higher sortilin levels than those with the GG and GA genotypes (P=0.000); the same tendency was also observed in the levels of the proinflammatory cytokines IL-1β (P=0.003) and TNF-α (P=0.000). Similarly, GG carriers of rs464218 with increased sortilin levels were found to be at increased risk for CHD (P=0.014). The levels of IL-1β (P=0.025) and IL-6 (P=0.015) were also increased in these patients. Conclusion: Our findings reveal that high sortilin levels may interact with inflammatory response to contribute to the occurrence of CHD. Considering that our clinical evidence suggests for the first time that sortilin involves in inflammatory response in CHD, the mechanistic role of sortilin in the progression of CHD deserves detailed investigation.

Effects of gut microbiota and gut-derived lipopolysaccharide on patients with coronary heart disease

“…Accumulating data indicates that chronic in ammation is controlled by proin ammatory cytokines including IL-1β, IL-6 [20], and TNF-α [21]via immune responses including the recruitment of in ammatory cells to the site of injury and the promotion of adverse vascular smooth muscle cell remodeling play a critical role in atherogenesis. Our study found a reduction of TNF, IL-1, and IL-6 in the CHD group, elevated levels of proin ammatory cytokines were also observed in CHD patients in Han's study [22]. Moreover, an animal model study showed that the transfer of BM de cient in sortlin which is a high-a nity receptor for the proin ammatory cytokines IL-6 and IFN-γ into irradiated atherosclerotic mice reduced atherosclerosis and systemic markers of in ammation [13].…”

Association of the PSRC1 rs599839 Variant with Coronary Artery Disease in a Mexican Population

“…This rs599839 polymorphism is located on the 1p13.3 chromosomal region near the SORT1 (sortilin-1) gene, which encodes the VPS10P domain-sorting receptors involved in intracellular protein trafficking and the modulation of hepatic very-low-density protein secretion [ 25 , 26 ]. The frequency of the rs599839 polymorphism in the Chinese population has been reported to be higher in CAD patients compared with healthy controls (OR = 8.37, 95% CI: 1.70–41.0); in addition, CAD patients with the AA genotype display higher sortilin levels than those with the GG and GA genotypes (391.25 ± 128.24 ng/L vs. 314.70 ± 64.65 ng/L, p = 0.000) [ 27 ]. Other studies have also shown that the increase in SORT1 expression was negatively correlated with LDLc levels [ 28 ].…”

Study on the mechanism of Gualou Xiebai Guizhi decoction (GLXBGZD) in the treatment of coronary heart disease based on network pharmacology

“…[ 23 ] Activating proinflammatory factors, such as IL-6 and TNF, can disrupt the endothelial function of blood vessels and accelerate the rupture of plaques, thus accelerating the onset of coronary atherosclerosis. [ 24 ] Therefore, inhibition of inflammatory factor activation can reduce the adverse incidence of cardiovascular events in CHD. VEGFA has been shown to promote microvessel formation and development by binding to vascular endothelial cell receptors to induce their differentiation, proliferation, and migration.…”