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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1104.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Circulating Tissue Kallikrein Levels Correlate With Severity of Carotid Atherosclerosis

Paolo Porcu; Costanza Emanueli; Elisa Desortes; Giovanni M. Marongiu; Franco Piredda; Lee Chao; Julie Chao; Paolo Madeddu

From the Institute of Internal Medicine (P.M.) and Vascular Surgery (P.P., G.M.M., F.P.), Medical University of Sassari, Sassari, Italy; the Experimental Medicine and Gene Therapy Section (C.E., E.D., P.M.), National Institute of Biostructures and Biosystems, Osilo, Italy; and the Department of Biochemistry and Molecular Biology, Medical University of South Carolina (L.C., J.C.), Charleston, SC.

Correspondence to Dr Paolo Madeddu, Institute of Internal Medicine, Viale S. Pietro 8, 07100 Sassari, Italy. E-mail madeddu{at}yahoo.com

Background— Vascular growth factors are upregulated in stroke patients, but it remains unknown if they correlate with carotid atherosclerosis.

Methods and Results— A case-control study was conducted to determine: (1) possible association between biomarkers of angiogenesis or inflammation and carotid stenosis; and (2) the impact of revascularization on the same biomarkers. Circulating vascular endothelial growth factor (VEGF), basic fibroblast GF (bFGF), tissue kallikrein (tK), and high-sensitivity C-reactive protein (hs-CRP) were measured in 89 patients with carotid obstruction and 45 age-matched controls. Patients were stratified as <50% carotid stenosis (CAS; n=16); 50% to 69% CAS (n=12); 70% to 99% CAS (n=43); and carotid occlusion (CAO; n=18). No association was found between VEGF, bFGF, or hs-CRP and obstruction grading. TK augmented from 360±30 in <50% CAS (P=NS versus controls) to 509±72 in moderate CAS (P<0.05), 1159±178 in high-grade CAS (P<0.02), and 1616±403 pg/mL in CAO (P<0.01). A threshold of 508 pg/mL provided the maximized predictive value of high-grade obstruction. After revascularization, tK decreased from 1410±352 to 782±86 pg/mL (P<0.01), whereas no change was detected in nonoperated cases. Hs-CRP was unaffected by revascularization.

Conclusions— Angiogenic factors are heterogeneously expressed in patients with carotid atherosclerosis. The tK measurement may be useful for the diagnosis and monitoring of atherosclerotic disease.

A case-control study was conducted to determine possible association between biomarkers of angiogenesis or inflammation and characteristics of carotid stenosis. No association was found between circulating VEGF, bFGF, or hs-CRP and obstruction grading. Circulating tissue kallikrein increasingly augmented across categories of stenosis severity and upregulation was reversed by revascularization.

Key Words: brain • growth factors • angiogenesis • atherosclerosis • inflammation • revascularization