A kallikrein-like enzyme in the aorta of normotensive and hypertensive rats.

Madeddu, Paolo; Varoni, Maria Vittoria; Demontis, Maria Piera; Fattaccio, Maria Caterina; Parpaglia, Paolo Pinna; Glorioso, Nicola

doi:10.1161/01.hyp.23.6.899

Cited by 14 publications

(4 citation statements)

References 14 publications

(14 reference statements)

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“…The presence of tissue kallikrein in the blood vessels has been reported by many investigators (Madeddu et al, 1994;Nolly and Nolly, 1998;Nolly et al, 1994;Oza and Goud, 1992;Saed et al, 1990). The endogenous kinin may be generated by the tissue kallikrein-type proteases located in the vessels in the granulation tissues.…”

Section: Figurementioning

confidence: 68%

Suppressed Angiogenesis in Kininogen-Deficiencies

Hayashi

Aoki

Yoshida

et al. 2002

Laboratory Investigation

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SUMMARY:We investigated whether the kinin-generating system enhanced angiogenesis in chronic and proliferative granuloma and in tumor-surrounding stroma. In rat sponge implants, angiogenesis was gradually developed in normal Brown Norway Kitasato rats (BN-Ki). The development of angiogenesis was significantly suppressed in kininogen-deficient Brown Norway Katholiek rats (BN-Ka). The angiogenesis enhanced by basic fibroblast growth factor was also significantly less marked in BN-Ka than in BN-Ki. Naturally occurring angiogenesis was significantly suppressed by B 1 or B 2 antagonist. mRNA of vascular endothelial growth factor was more highly expressed in the granulation tissues in BN-Ki than in BN-Ka. Daily topical injections of aprotinin, but not of soy bean trypsin inhibitor, suppressed angiogenesis. Daily topical injections of low-molecular weight kininogen enhanced angiogenesis in BN-Ka. Topical injections of serum from BN-Ki, but not from BN-Ka, also facilitated angiogenesis in BN-Ka. FR190997, a nonpeptide mimic of bradykinin, promoted angiogenesis markedly, with concomitant increases in vascular endothelial growth factor mRNA. Angiogenesis in the granulation tissues around the implanted Millipore chambers containing Walker-256 cells was markedly more suppressed in BN-Ka than in BN-Ki. Our results suggest that endogenous kinin generated from the tissue kallikrein-kinin system enhances angiogenesis in chronic and proliferative granuloma and in the stroma surrounding a tumor. Thus, the agents for the kinin-generating system and/or kinin receptor signaling may become useful tools for controlling angiogenesis. (Lab Invest 2002, 82:871-880).

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Section: Figurementioning

confidence: 68%

Suppressed Angiogenesis in Kininogen-Deficiencies

Hayashi

Aoki

Yoshida

et al. 2002

Laboratory Investigation

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“…24 Previous studies reported that 20% to 30% of the vascular kallikrein in the rat is present in the active form. 25,26 These combined results indicated that VSMCs contain a kallikrein-activating mechanism. However, the ratio of active versus inactive forms of recombinant human tissue kallikrein expressed in rat aorta after gene transfer remains to be evaluated.…”

Section: Discussionmentioning

confidence: 88%

Kallikrein Gene Delivery Inhibits Vascular Smooth Muscle Cell Growth and Neointima Formation in the Rat Artery After Balloon Angioplasty

et al. 1999

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Abstract-Tissue kallikrein cleaves kininogen substrate to produce vasoactive kinin peptides that have been implicated in the proliferation of vascular smooth muscle cells (VSMCs). To explore potential roles of the kallikrein-kinin system in vascular biology, we evaluated the effects of adenovirus-mediated human kallikrein gene delivery on the growth of primary cultured VSMCs and in balloon-injured rat artery in vivo. Kallikrein gene transfer into cultured rat VSMCs resulted in time-dependent secretion of recombinant human tissue kallikrein and inhibition of cell proliferation. Balloon angioplasty reduced endogenous rat tissue kallikrein mRNA and protein levels at the injured site. In rats that received adenovirus-mediated human kallikrein gene delivery, we observed a 39% reduction in intima/media ratio at the injured vessel after delivery compared with that of rats that received control virus (nϭ8, PϽ0.01). Icatibant, a specific bradykinin B 2 receptor antagonist, blocked the protective effect and reversed the intima/media ratio to that of the control rats (nϭ5, PϽ0.01). After gene delivery, human kallikrein mRNA was identified at the injured vessel and a 3-fold increase occurred in kininogenase activity. cAMP and cGMP levels in balloon-injured aorta increased significantly at 4, 7, and 14 days after kallikrein gene delivery, but icatibant abolished the increase. These results provide new insights into the role of the vascular kallikrein-kinin system and have significant implications for gene therapy to treat restenosis or atherosclerosis. (Hypertension. 1999;34:164-170.)

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“…Biochemical and histological studies indicate that kallikrein is expressed in human vascular wall, 31 and levels of expression seem to be variably affected in different forms of hypertension. 32 Preliminary immunohistochemical findings suggest that tK is also expressed in atherosclerotic carotid arteries (Madeddu P, unpublished results 2004). However, the absence of correlation with indicators of plaque instability favors the possibility that tK increases in peripheral circulation as a consequence of chronic hemodynamic changes related to the stenosis.…”

Section: Perspectivesmentioning

confidence: 98%

Circulating Tissue Kallikrein Levels Correlate With Severity of Carotid Atherosclerosis

Porcu

Emanueli

Desortes

et al. 2004

ATVB

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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.

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A kallikrein-like enzyme in the aorta of normotensive and hypertensive rats.

Cited by 14 publications

References 14 publications

Suppressed Angiogenesis in Kininogen-Deficiencies

Suppressed Angiogenesis in Kininogen-Deficiencies

Kallikrein Gene Delivery Inhibits Vascular Smooth Muscle Cell Growth and Neointima Formation in the Rat Artery After Balloon Angioplasty

Circulating Tissue Kallikrein Levels Correlate With Severity of Carotid Atherosclerosis

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