The tissue kallikrein-kinin system protects against cardiovascular and renal diseases and ischemic stroke independently of blood pressure reduction
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Julie Chao
Abstract
Tissue kallikrein (hK1) cleaves low-molecular-weight kininogen to produce kinin peptide, which binds to kinin receptors and triggers a wide spectrum of biological effects. Tissue kallikrein levels are reduced in humans and in animal models with hypertension, cardiovascular and renal diseases. Transgenic mice or rats over-expressing human tissue kallikrein or kinin B2 receptor are permanently hypotensive, and somatic kallikrein gene delivery reduces blood pressure in several hypertensive rat models. Moreover, kallikrein gene delivery or kallikrein protein infusion can directly improve cardiac, renal and neurological function without blood pressure reduction. Kallikrein has pleiotropic effects in inhibiting apoptosis, inflammation, proliferation, hypertrophy and fibrosis, and promoting angiogenesis and neurogenesis in different experimental animal models. Kallikrein's effects can be blocked by kinin B2 receptor antagonists. Mechanistically, tissue kallikrein/kinin leads to increased nitric oxide levels and Akt activation, and reduced reactive oxygen species formation, TGF-β1 expression, MAPK and nuclear factor-κB activation. Our studies indicate that tissue kallikrein, through the kinin B2 receptor and nitric oxide formation, can protect against oxidative damage in cardiovascular and renal diseases and ischemic stroke. These novel findings suggest that kallikrein/kinin may serve as new drug targets for the prevention and treatment of heart failure, renal disease and stroke in humans.
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©2006 by Walter de Gruyter Berlin New York
Articles in the same Issue
- The First International Symposium on Kallikreins
- A comprehensive nomenclature for serine proteases with homology to tissue kallikreins
- The kallikrein world: an update on the human tissue kallikreins
- Cellular distribution of human tissue kallikreins: immunohistochemical localization
- The tissue kallikrein-kinin system protects against cardiovascular and renal diseases and ischemic stroke independently of blood pressure reduction
- Proteinase-mediated cell signalling: targeting proteinase-activated receptors (PARs) by kallikreins and more
- Recombinant kallikrein expression: site-specific integration for hK6 production in human cells
- Kallikrein-related peptidase (KLK) family mRNA variants and protein isoforms in hormone-related cancers: do they have a function?
- The role of kallikrein-related peptidases in prostate cancer: potential involvement in an epithelial to mesenchymal transition
- Human kallikrein 10, a predictive marker for breast cancer
- Activation and enzymatic characterization of recombinant human kallikrein 8
- Human tissue kallikrein 9: production of recombinant proteins and specific antibodies
- The human kallikrein 10 promoter contains a functional retinoid response element
- Human kallikrein 4: enzymatic activity, inhibition, and degradation of extracellular matrix proteins
- Kallikrein-related peptidase 14 may be a major contributor to trypsin-like proteolytic activity in human stratum corneum
- A sensitive proximity ligation assay for active PSA
- Multiple mechanisms underlie the aberrant expression of the human kallikrein 6 gene in breast cancer
- Expression of the human kallikrein genes 10 (KLK10) and 11 (KLK11) in cancerous and non-cancerous lung tissues
- mRNA expression analysis of human kallikrein 11 (KLK11) may be useful in the discrimination of benign prostatic hyperplasia from prostate cancer after needle prostate biopsy
- The epigenetic basis for the aberrant expression of kallikreins in human cancers
- Improved prostate cancer detection with a human kallikrein 11 and percentage free PSA-based artificial neural network
- Overexpression of the human tissue kallikrein genes KLK4, 5, 6, and 7 increases the malignant phenotype of ovarian cancer cells
- Inhibition profiles of human tissue kallikreins by serine protease inhibitors
- Kallikrein-mediated cell signalling: targeting proteinase-activated receptors (PARs)
Articles in the same Issue
- The First International Symposium on Kallikreins
- A comprehensive nomenclature for serine proteases with homology to tissue kallikreins
- The kallikrein world: an update on the human tissue kallikreins
- Cellular distribution of human tissue kallikreins: immunohistochemical localization
- The tissue kallikrein-kinin system protects against cardiovascular and renal diseases and ischemic stroke independently of blood pressure reduction
- Proteinase-mediated cell signalling: targeting proteinase-activated receptors (PARs) by kallikreins and more
- Recombinant kallikrein expression: site-specific integration for hK6 production in human cells
- Kallikrein-related peptidase (KLK) family mRNA variants and protein isoforms in hormone-related cancers: do they have a function?
- The role of kallikrein-related peptidases in prostate cancer: potential involvement in an epithelial to mesenchymal transition
- Human kallikrein 10, a predictive marker for breast cancer
- Activation and enzymatic characterization of recombinant human kallikrein 8
- Human tissue kallikrein 9: production of recombinant proteins and specific antibodies
- The human kallikrein 10 promoter contains a functional retinoid response element
- Human kallikrein 4: enzymatic activity, inhibition, and degradation of extracellular matrix proteins
- Kallikrein-related peptidase 14 may be a major contributor to trypsin-like proteolytic activity in human stratum corneum
- A sensitive proximity ligation assay for active PSA
- Multiple mechanisms underlie the aberrant expression of the human kallikrein 6 gene in breast cancer
- Expression of the human kallikrein genes 10 (KLK10) and 11 (KLK11) in cancerous and non-cancerous lung tissues
- mRNA expression analysis of human kallikrein 11 (KLK11) may be useful in the discrimination of benign prostatic hyperplasia from prostate cancer after needle prostate biopsy
- The epigenetic basis for the aberrant expression of kallikreins in human cancers
- Improved prostate cancer detection with a human kallikrein 11 and percentage free PSA-based artificial neural network
- Overexpression of the human tissue kallikrein genes KLK4, 5, 6, and 7 increases the malignant phenotype of ovarian cancer cells
- Inhibition profiles of human tissue kallikreins by serine protease inhibitors
- Kallikrein-mediated cell signalling: targeting proteinase-activated receptors (PARs)