Stromal Cell-Derived Factor-1α as a Novel Biomarker for Hyperlipidemia

Abstract

Stromal cell-derived factor-1 (SDF-1) is expressed in a wide variety of organs, such as heart, and plays a pivotal role in the mobilization of hematopoietic stem and progenitor cells in bone marrow. SDF-1α, a common subtype of SDF-1, may control hematopoiesis and angiogenesis, but its role in the pathogenesis of hyperlipidemia is unknown. The aim of this study was to determine the role of SDF-1α in the pathogenesis of hyperlipidemia. First, log-transformed SDF-1α serum levels (logSDF-1α) were significantly higher in male patients with borderline high lipid profile (BHLP; n = 28; 2.15 ± 0.08 ng/ml) compared to control subjects (n = 37; 1.94 ± 0.06 ng/ml; P < 0.01). The logSDF-1α in male patients with high lipid profile (HLP; n = 33; 1.95 ± 0.08 ng/ml) were lower than BHLP patients (P < 0.01). The logSDF-1α was positively associated with HDL-C only in female patients (n = 125; r = 0.379, P = 0.016). These results suggest the different pathophysiology in male and female patients with hyperlipidemia. Moreover, flow cytometry analysis showed that expression of the SDF-1α receptor, CXC-chemokine receptor 4, was lower in peripheral blood mononuclear cells of patients with BHLP (n = 10) and HLP (n = 10), compared to control subjects (n = 10; P < 0.001). Lastly, peripheral blood leukocyte, neutrophil and lymphocyte counts were higher in BHLP patients (n = 62; P < 0.05). Taken together, we suggest SDF-1α as a biomarker of hyperlipidemia that may be helpful to uncover the pathogenesis of hyperlipidemia.

Decreased Serum Stromal Cell-Derived Factor-1 in Patients with Familial Hypercholesterolemia and Its Strong Correlation with Lipoprotein Subfractions

“…Although an elevated amount of triglyceride-rich particles is not characteristic of FH, the disorder is often associated with other conditions including overweight, which may lead to the elevation of triglyceride-rich particles such as VLDL and IDL, leading to elevated serum triglycerides. Formerly, data suggested that inflammatory cytokines (TNFα and IL-6) may have a suppressive effect on SDF-1 in male patients with hyperlipidemia [6]. Although we could not find correlations between inflammatory markers and SDF-1, higher hsCRP indicating enhanced systemic inflammation may diminish SDF-1's production in HeFH.…”

“…Furthermore, there was a non-significant negative correlation between SDF-1 and the TC/HDL-C ratio. SDF-1 was positively associated with HDL-C in female patients only [6]. In another study, increasing quartiles of SDF-1 were associated with higher LDL-C and triglycerides, while HDL-C decreased across SDF-1 quartiles in participants of the Framingham Heart Study.…”

“…Some former studies suggested an association between serum SDF-1 and hyperlipidemia, however, the exact nature of the relationship seems to be uncertain. Serum SDF-1 was found to be elevated in male patients with mild hyperlipidemia but decreased in severe hyperlipidemia [6]. It was reported that hypercholesterolemia disturbs the bone marrow SDF-1/CXCR4 axis, generating a proatherogenic state in mice [7].…”

A finger in every pie – The versatility of chemokines

“…SDF-1α is expressed in various organs and is inter alia associated with heart failure and all-cause mortality risk [ 10 ]. It has been suggested as a potential biomarker for hyperlipidemia since it plays a pivotal role in the mobilization of hematopoietic stem and progenitor cells in bone marrow [ 11 ].…”

Role and implications of the CXCL12/CXCR4/CXCR7 axis in atherosclerosis: still a debate

“…CXCL12 levels are also associated with hyperlipidaemia. Serum CXCL12 was found to be elevated in hyperlipidaemia patients, suggesting its role as a biomarker [ 91 ]. In addition, statins, which are used to treat hyperlipidaemia, cause a decrease in CXCL12 levels.…”