Abstract 5870: Increased Expression of Biglycan and Phospholipid Transfer Protein in Calcific Aortic Valve and their Relationships with Inflammation and Small, Dense LDL in Patients with Aortic Stenosis
Introduction: Small, dense LDLs are associated with a faster progression rate of aortic stenosis (AS) and with increased valvular accumulation of oxidized-LDL. Biglycan (BGN), a proteoglycan which binds to apolipoproteins like ApoB in tissues, is possibly an important component involved in lipoprotein-lipid retention, inflammation and AS development. Furthermore, local expression of phospholipid transfer protein (PLTP) has been found to modify and to promote the retention of lipoproteins. Thus, we sought to determine whether small, dense LDLs were associated with mechanisms involved in the retention of lipoproteins in patients with AS.
Methods: Aortic valve and fasting blood plasma samples of 80 patients (mean age: 68.89±1.26) who underwent a surgery for a severe AS were retrieved. A complete plasma lipoprotein-lipid blood profile including the size of LDL particles (measured by 2–16% gradient gel electrophoresis) were determined. AS valves were studied by immunohistochemistry for the expression of biglycan (BGN), apolipoproteins and inflammatory cytokines such as TNF-α and NFκB. Expression of BGN, TNF-α, NFκB, and PLTP were determined by real-time PCR.
Results: BGN was found in all AS valves where it co-localized with apoB-100, ox-LDL, macrophages, TNF-α, and PLTP. In quantitative analyses, BGN and PLTP were significantly increased in AS valves. Quantitative RT-PCR shows that BGN, TNF-α, and NFκB were negatively correlated with the LDL size (r=−0.26, p=0.015; r=−0.22, p=0.05 and r=−0.3, p=0.01). In turn, BGN expression was positively correlated with TNF-α (r=0.36, p=0.002), NFκB (r=0.49, p<0.0001), and PLTP (r=0.56, p<0.0001). After corrections for covariate including age, gender and insulin resistance (HOMA index), LDL size was found to be significantly associated with valvular expression of BGN (r2 adjusted= 0.38; p<0.006).
Conclusion: Patients with AS carrying small, dense LDLs have increased valvular expression of biglycan which is, in turn, associated with inflammatory markers and PLTP expression. Thus, the process related to lipoproteins retention is significantly activated in patients with AS carrying small, dense LDLs, in whom the disease process might be amplified.