Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.2.2.7 (heparinase)
 1,270 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipoprotein lipase (LPL) is central to triacylglycerol (TG) metabolism, having both hydrolytic and bridging functions. The common LPL gene variant D9N is associated with raised TG, reduced HDL-cholesterol concentrations and increased risk of coronary artery disease (CAD). To investigate the functional basis for the phenotype in N9 carriers, CHO K1 cells were stably transfected with wild type (D9) or mutant (N9) LPL cDNA. LPL RNA expression levels, monomer-to-dimer ratios, and dimer specific activities were similar in D9 and N9 cells. Significantly enhanced binding (4.6-fold) and internalisation (2.6-fold) of 125I-LDL by N9 compared with D9 cells was eradicated by pre-treatment with either heparin or heparinase, confirming involvement of LPL and cell surface proteoglycans. N9 cells bound and internalised 3.8- and 4.4-fold more oxidised 125I-LDL, respectively, than D9 cells (both P<0.0001). Binding of monocytes was 7-fold greater to plates coated with purified LPL-N9 dimer compared with LPL-D9 (P<=0.005). Thus once on the cell surface, LPL-N9 enhances bridging, as assessed both by LDL binding and internalisation, and monocyte adhesion. This augmented LPL-N9 bridging provides a mechanism for the reported increased CAD risk in N9 carriers.
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PMID:Enhanced bridging function and augmented monocyte adhesion by lipoprotein lipase N9: insights into increased risk of coronary artery disease in N9 carriers. 1253 36