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The Association Between Sortilin and Inflammation in Patients with Coronary Heart Disease
Wenxiu Han1, Zhijie Wei2, Hailiang Zhang1
1Department of Pharmacy, Jining First People's Hospital, Jining Medical University, Jining 272011, People's Republic of China.
Insights
High sortilin levels are linked to increased inflammation and coronary heart disease (CHD). This study found sortilin and inflammatory cytokines were elevated in CHD patients, suggesting a role in disease development.
Area of Science:
- Cardiovascular Disease Research
- Immunology
- Genetics
Background:
- Inflammation is a significant factor in coronary heart disease (CHD).
- Sortilin, a sorting receptor, plays a role in regulating inflammatory responses.
- Understanding the relationship between sortilin, inflammation, and CHD is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To investigate the association between circulating sortilin levels, proinflammatory cytokine levels, and the occurrence of CHD.
- To determine if sortilin levels correlate with specific inflammatory markers (IL-1β, IL-6, TNF-α) in CHD patients.
- To explore the potential link between sortilin gene polymorphisms and CHD risk.
Main Methods:
- A case-control study involving 227 CHD patients and 101 healthy controls.
- Serum levels of sortilin and proinflammatory cytokines (IL-1β, IL-6, TNF-α) were measured using DAS-ELISA.
- Linear regression, correlation analyses, and genotyping of six single-nucleotide polymorphisms (SNPs) in sortilin and SORL1 genes were performed.
Main Results:
- CHD patients exhibited significantly higher levels of sortilin, IL-1β, IL-6, and TNF-α compared to healthy controls.
- Sortilin levels showed a significant positive correlation with IL-1β, IL-6, and TNF-α.
- Specific sortilin polymorphisms (rs599839 AA and rs464218 GG) were associated with increased sortilin levels, higher inflammation markers, and elevated CHD risk.
Conclusions:
- Elevated sortilin levels may contribute to the development of CHD by interacting with the inflammatory response.
- This study provides the first clinical evidence linking sortilin to inflammation in the context of CHD.
- Further research is warranted to elucidate the precise mechanistic role of sortilin in CHD progression.
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 single-nucleotide 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.
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