Circulating Tissue Kallikrein Levels Correlate With Severity of Carotid Atherosclerosis

Abstract

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.

Endothelial Colony Forming Capacity is Related to C-Reactive Protein Levels in Healthy Subjects

“…Unfortunately, angiogenesis biomarkers show wide ranges that overlap in subjects with disease and in those without it, and studies on healthy subjects are lacking. For this reason, various cutoff points should be tested for their ability to detect disease even at subclinical stage, followed by definition of threshold levels with maximized sensitivity and specificity as suggested by a recent paper providing evidences that angiogenesis biomarkers are heterogeneously expressed in patients with carotid atherosclerosis (Porcu et al 2004). At systemic level cytokine activation, and in particular IL-6, is followed by CRP secretion from the liver which acts as ligand-binding protein for complement.…”

Genetic and dietary control of plasma tissue kallikrein secretion and urinary kinins exretion in man

“…Tissue kallikrein activity in plasma cannot be accurately measured, unlike in urine, because of the interference of other plasma proteases. Plasma tissue kallikrein can, however, be quantified immunologically [15]. Our findings indicate that immunoreactive tissue kallikrein levels in plasma are genetically determined, and reduced by the R53H mutation; they also show that these levels are influenced by sodium and potassium intake.…”

“…Plasma tissue kallikrein measurements Immunoreactive tissue kallikrein was assayed in plasma by an enzyme-linked immunosorbent assay (ELISA), as previously described [15]. This assay recognizes free kallikrein in plasma, and both inactive prokallikrein and active kallikrein.…”

Role of human tissue kallikrein in gastrointestinal stromal tumour invasion

“…We previously reported that hK1 levels are remarkably elevated in peripheral blood of patients with critical carotid artery obstruction and normalised after endarterectomy (Porcu et al , 2004). Only one subject of this series showed persistently high hK1 levels before and after revascularisation (1456 and 1681 pg ml −1 , respectively).…”

“…Immunoreactive hK1 in cell culture supernatants and blood was measured by ELISA as previously reported (Wang et al , 1995; Porcu et al , 2002, 2004) and hK1 activity was assayed using the chromogenic substrate S-2266, following the manufacturer's instructions (Chromogenix, Milano, Italy) and as previously described (Madeddu et al , 1993). …”