title: Intravascular free tissue factor pathway inhibitor is inversely correlated with HDL cholesterol and postheparin lipoprotein lipase but proportional to apolipoprotein A-II.
abstract: To elucidate the distribution and clinical implications of tissue factor pathway inhibitor (TFPI) concentrations, we measured TFPI levels consisting of preheparin free, lipoprotein-bound (Lp-bound), and endothelial cell-anchor pools in 156 patients with coronary artery disease (average age, 61.2+/-9.1 years; range, 32 to 78 years) by heparin infusion (50 IU/kg) and compared them with the preheparin TFPI levels of 229 healthy subjects (average age, 59. 6+/-9.4 years; range, 41 to 80 years). The patients had lower preheparin free TFPI and lower HDL cholesterol (HDL-C) levels than the healthy subjects with equivalent Lp-bound forms (free TFPI, 15. 9+/-6.5 versus 19.2+/-8.1 ng/mL). In a partial correlation analysis, the preheparin free TFPI levels were shown to be inversely correlated with the HDL-C concentrations in both the patients (r=-0. 454, P<0.001) and the healthy subjects (r=-0.136, P<0.05). As determined by comparison of preheparin and postheparin plasma, the patients generally showed preheparin free TFPI <10%, Lp-bound TFPI at 30%, and endothelial cell-anchor TFPI at 60%. When the patients were divided into 4 categories by their LDL cholesterol (LDL-C, 130 mg/dL) and HDL-C (40 mg/dL) levels to specify their coronary risks, the low-HDL-C groups had significantly increased preheparin and postheparin free TFPI levels and decreased postheparin LPL levels, whereas the high-LDL-C groups showed increased levels of Lp-bound TFPI. In a partial correlation analysis, we found a proportional relation between postheparin free TFPI and apolipoprotein A-II (r=0. 5327) and between HDL-C and LPL (r=0.4906), whereas postheparin free TFPI was inversely correlated with HDL-C (r=-0.4280) and postheparin LPL (r=-0.4791). The inverse relationship between TFPI and LPL suggests that increased free TFPI concentrations as a compensatory response of the endothelium to prevent atherothrombotic processes compete with and displace LPL on endothelial surface, resulting in reduced LPL and low HDL-C.
authors.affiliation: National Cardiovascular Center Research Institute, Osaka, Japan. akitok@ri.ncvc.go.jp
authors.forename: A
authors.initials: A
authors.lastname: Kawaguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Miyao
authors.forename: T
authors.initials: T
authors.lastname: Noguchi
authors.forename: H
authors.initials: H
authors.lastname: Nonogi
authors.forename: M
authors.initials: M
authors.lastname: Yamagishi
authors.forename: K
authors.initials: K
authors.lastname: Miyatake
authors.forename: Y
authors.initials: Y
authors.lastname: Kamikubo
authors.forename: K
authors.initials: K
authors.lastname: Kumeda
authors.forename: M
authors.initials: M
authors.lastname: Tsushima
authors.forename: A
authors.initials: A
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Kato
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016633:Apolipoprotein A-II / Q000097:blood*; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood*; D005260:Female; D006493:Heparin; D006801:Humans; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000097:blood*; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D012307:Risk Factors
chemical_list: D016633:Apolipoprotein A-II; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D006493:Heparin; D008071:Lipoprotein Lipase