Increased tissue kallikrein levels in type 2 diabetes

Campbell, Duncan J.; Kladis, Athena; Zhang, Yuan; Jenkins, Alicia J.; Prior, David; Yii, Michael; Kenny, James F.; Black, M. Jane; Kelly, Darren J.

doi:10.1007/s00125-009-1645-8

Cited by 36 publications

(25 citation statements)

References 30 publications

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“…Statin therapy improves endothelial function and possibly causes kinin generation at the endothelial surface, but the association between these drugs and the circulating kallikrein-kinin system has not been widely studied. A publication in type 2-diabetic patients found no differences in circulating bradykinin and other peptides and proteins of the kallikrein-kinin system following statin therapy [37] whereas our results suggest that statins may improve the patients' inflammatory status via the kallikrein-kinin system. Note that no patients of this study received angiotensinconverting enzyme inhibitors, which are well known to increase levels of bradykinin in blood by inhibiting its degradation [38] .…”

Section: Color Version Available Onlinecontrasting

confidence: 54%

Proteomic Approach to the Study of Statin Pleiotropy in Kidney Transplant Patients

Pérez

Navarro-Muñoz²,

Mas³

et al. 2011

Pharmacology

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Background/Aims: Statins are prescribed in kidney transplant recipients in order to manage dyslipidemia, a common complication in these patients. The efficacy of statins in reducing cholesterol levels has been accompanied by pleiotropic effects. Fifty-four kidney transplant patients were included in the present study, the objective of which was to ascertain the effect of 12 weeks of atorvastatin therapy (10 mg/day) on the patients’ lipid profile, renal function, markers of inflammation and plasma peptide profile. Methods: Biochemical variables were determined with a routine clinical laboratory analyzer, and the proteomic approach was based on magnetic particle-assisted sample processing coupled to mass spectrometry readout. Results: Atorvastatin therapy improved the lipid profile of patients and caused significant changes in their plasma peptide profile; peptides with m/z 1063 and 1898 decreased after treatment and were identified as fragments derived from molecules involved in vascular inflammation, i.e. high-molecular-weight kininogen and complement factor C4, respectively. Conclusion: These findings may contribute to the growing body of evidence of the anti-inflammatory actions attributed to statins, by which these drugs could improve these patients’ clinical status.

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Section: Color Version Available Onlinecontrasting

confidence: 54%

Proteomic Approach to the Study of Statin Pleiotropy in Kidney Transplant Patients

Pérez

Navarro-Muñoz²,

Mas³

et al. 2011

Pharmacology

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“…Vascular calcification is a common complication of diabetic vasculopathy and atherosclerosis, and levels of elastases and kallikreins are elevated in diabetic patients as well as in atherosclerotic lesions 42, 43 . Our observations point toward new ways of explaining vascular calcification in these conditions and may lead to new strategies for limiting calcification.…”

Section: Discussionmentioning

confidence: 99%

Serine Protease Activation Essential for Endothelial–Mesenchymal Transition in Vascular Calcification

Yao

Guihard

Blázquez‐Medela

et al. 2015

Circulation Research

125

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Rationale Endothelial cells have the ability to undergo endothelial-mesenchymal transitions (EndMTs), by which they acquire a mesenchymal phenotype and stem-cell like characteristics. We previously found that EndMTs ocurred in the endothelium deficient in matrix Gla protein (MGP) enabling endothelial cells to contribute cells to vascular calcification. However, the mechanism responsible for initiating EndMTs is not fully understood. Objective To determine the role of specific serine proteases and sex determining region Y-box 2 (Sox2) in the initiation of EndMTs. Methods and Results In this study, we used in vivo and in vitro models of vascular calcification to demonstrate that serine proteases and Sox2 are essential for the initiation of EndMTs in MGP-deficient endothelium. We showed that expression of a group of specific serine proteases was highly induced in endothelial cells at sites of vascular calcification in Mgp null aortas. Treatment with serine protease inhibitors decreased both stem-cell marker expression and vascular calcification. In human aortic endothelial cells, this group of serine proteases also induced EndMTs, and the activation of proteases was mediated by Sox2. Knockdown of the serine proteases or Sox2 diminished EndMTs and calcification. Endothelial-specific deletion of Sox2 decreased expression of stem-cell markers and aortic calcification in MGP-deficient mice. Conclusions Our results suggest that Sox2-mediated activation of specific serine proteases is essential for initiating EndMTs, and thus, may provide new therapeutic targets for treating vascular calcification.

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“…This may also suggest that high levels of tissue kallikrein in diabetic patients might be a predisposing factor in the induction of type 2 diabetes due to the inhibition of glucose transfer to the tissues [22]. Plasma levels of tissue kallikreinhave been reported to be increased in type 2 diabetes as previously reported [23] In the present study however, we also observed high concentrations of plasma tissue kallikrein , which presumably be due to the hyperactivity of the BK-forming system to induce systemic metabolic abnormalities. It has been reported that tissue kallikrein activates B2R directly without BK generation [24].…”

Section: Commentarymentioning

confidence: 70%

Bradykinin System and Type 2 Diabetes

Sharma¹

2016

Int J Clin Pharmacol Pharmacother

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Increased tissue kallikrein levels in type 2 diabetes

Cited by 36 publications

References 30 publications

Proteomic Approach to the Study of Statin Pleiotropy in Kidney Transplant Patients

Proteomic Approach to the Study of Statin Pleiotropy in Kidney Transplant Patients

Serine Protease Activation Essential for Endothelial–Mesenchymal Transition in Vascular Calcification

Bradykinin System and Type 2 Diabetes

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